prednisolone and Androgen-Independent Prostatic Cancer

prednisolone has been researched along with Androgen-Independent Prostatic Cancer in 63 studies

Prednisolone: A glucocorticoid with the general properties of the corticosteroids. It is the drug of choice for all conditions in which routine systemic corticosteroid therapy is indicated, except adrenal deficiency states.
prednisolone : A glucocorticoid that is prednisone in which the oxo group at position 11 has been reduced to the corresponding beta-hydroxy group. It is a drug metabolite of prednisone.

Research

Studies (63)

Authors

Clinical Trials (12)

Trial Overview

Trial Outcomes

Part A: Number of Patients With Dose Limiting Toxicities (DLTs)

"DLTs were assessed by a Safety Review Committee (SRC) after a minimum of 3 patients had received at least 14 days of treatment in Part A.~A DLT was defined as any toxicity which was not a recognised AE of abiraterone or prednisolone, and was not attributable to the disease or disease-related processes under investigation, which occurred during a minimum period of 14 days treatment and which included: 1. haematological toxicity CTCAE v4.0 Grade 4 or higher present for more than 4 days (except anaemia); 2. non-haematological toxicity CTCAE v4.0 Grade 3 or higher including infection, corrected QT interval prolongation; 3. any other toxicity that was greater than that at baseline, was clinically significant and/or unacceptable, did not respond to supportive care, resulted in a disruption of dosing schedule of 7 days or more, or was judged to be a DLT by the SRC.~A DLT excluded alopecia and isolated laboratory changes of any grade without clinical sequelae or clinical significance." (NCT01972217)
Timeframe: From Day 1 for Cohort 1 and from Day 4 for Cohort 2 up to 14 days treatment with olaparib + abiraterone for 3 patients.

Part B: Median Best Percentage Change From Baseline in Circulating Tumour Cell (CTC) Level

"The median best percentage change from baseline in CTC levels was determined to assess the anti-tumour activity of olaparib when given in combination with abiraterone, compared with placebo given in addition to abiraterone.~The best percentage change was defined as the biggest CTC level reduction compared with baseline or smallest increase in the absence of a decrease." (NCT01972217)
Timeframe: From baseline, then every 4 weeks up to Week 24, and then every 12 weeks.

Part B: Median Best Percentage Change From Baseline in Prostate Specific Antigen (PSA) Levels

"The best percentage change from baseline in PSA levels was determined to assess the anti-tumour activity of olaparib when given in addition to abiraterone, compared with placebo given in addition to abiraterone.~The best percentage change was defined as the biggest reduction in PSA level compared with baseline or smallest increase in the absence of a decrease." (NCT01972217)
Timeframe: From baseline, then every 4 weeks up to Week 52, and then every 12 weeks.

Part B: Median Overall Survival (OS)

"OS was determined to assess the efficacy of olaparib when given in addition to abiraterone, compared with placebo given in addition to abiraterone.~OS was performed at the time of the analysis of rPFS, and the median OS, calculated using the Kaplan-Meier technique, is presented." (NCT01972217)
Timeframe: From baseline, every 12 weeks up to Week 72, then every 24 weeks up to 24 months.

Part B: Median Radiological Progression-Free Survival (rPFS) Time

"The efficacy of olaparib when given in combination with abiraterone was assessed by rPFS, defined as the time from randomisation to disease progression using Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1 (for soft tissue disease) and Prostate Cancer Working Group 2 (PCWG-2) (for bone disease) criteria, or death.~Progression using RECIST 1.1 criteria was defined as at least 20% increase from baseline in the sum of diameters of target lesions, progression of existing non-target lesions, or the appearance of at least 1 new lesion.~Progression using PCWG-2 criteria was determined if 2 or more new metastatic bone lesions were observed (with a total of at least 4 new lesions since baseline assessment if observed at the 12 week scan, or persistence of or increase in number of lesions if observed after the 12 week scan as determined by a confirmatory scan at least 6 weeks later or at next scheduled visit)." (NCT01972217)
Timeframe: From baseline, every 12 weeks up to Week 72, then every 24 weeks up to 24 months.

Part B: Median Time to Second Progression or Death (PFS2)

The efficacy of olaparib when given in combination with abiraterone was assessed by PFS2, defined by local standard clinical practice and included objective radiological progression by RECIST 1.1 (soft tissue), symptomatic progression, rise in PSA level or death in the absence of overall progression. (NCT01972217)
Timeframe: From randomisation until analysis cut-off date (up to approximately 3 years).

Part B: Percentage of Patients With at Least One Objective Response (Objective Response Rate [ORR])

"The overall radiological ORR was calculated to assess the anti-tumour activity of olaparib in combination with abiraterone, compared with placebo in combination with abiraterone.~The best overall ORR was defined as the percentage of patients with at least 1 visit response of complete response (CR) or partial response (PR) in soft tissue disease assessed by RECIST 1.1 and also bone scan status of non-progressive disease or non-evaluable for their bone scans assessed by PCWG-2.~CR: Disappearance of all target lesions. Reduction of pathological lymph nodes to <10 millimetres.~PR: At least a 30% decrease in the sum of diameters of target lesions from baseline.~The percentage of patients with a response is presented." (NCT01972217)
Timeframe: From baseline, then every 4 weeks up to Week 52, and then every 12 weeks.

Part B: Percentage of Patients With Progression Events or Death (rPFS)

"The efficacy of olaparib when given in combination with abiraterone was assessed by rPFS, defined as the time from randomisation to disease progression using RECIST version 1.1 (for soft tissue disease) and PCWG-2 (for bone disease) criteria, or death.~Progression using RECIST 1.1 criteria was defined as at least 20% increase from baseline in the sum of diameters of target lesions, progression of existing non-target lesions, or the appearance of at least 1 new lesion.~Progression using PCWG-2 criteria was determined if 2 or more new metastatic bone lesions were observed (with a total of at least 4 new lesions since baseline assessment if observed at the 12 week scan, or persistence of or increase in number of lesions if observed after the 12 week scan as determined by a confirmatory scan at least 6 weeks later or at next scheduled visit).~The percentage of patients with progression events is presented overall and according to RECIST 1.1 and/or PCWG-2 criteria, or death." (NCT01972217)
Timeframe: From baseline, every 12 weeks up to Week 72, then every 24 weeks up to 24 months.

Median Time to First Subsequent Therapy (TFST) and Median Time to Second Subsequent Therapy (TSST)

"The TFST and TSST were determined to assess the anti-tumour activity of olaparib when given in combination with abiraterone, compared with placebo given in addition to abiraterone.~TFST was defined as the time from randomisation to the earlier of first subsequent anti-cancer therapy start date following study treatment discontinuation, or death.~TSST was defined as the time from randomisation to the earlier of the second subsequent anti-cancer therapy start date following study treatment discontinuation, or death." (NCT01972217)
Timeframe: From randomisation until analysis cut-off date (up to approximately 3 years).

Part A Pharmacokinetics (PK): Olaparib Maximum Plasma Concentration at Steady State (Cmax,ss)

"Following multiple dosing to steady state of olaparib 300 mg bid, the Cohort 2 olaparib Cmax,ss is presented for olaparib monotherapy and for olaparib given in combination with abiraterone.~Only patients with data available for analysis at each time point are presented." (NCT01972217)
Timeframe: PK sampling for Cohort 2 Group 1 was between Days 3 and 7 for olaparib, and Days 4 and 8 for olaparib and abiraterone. PK sampling for Cohort 2 Group 2 was between Days 5 and 7 for abiraterone, and Days 6 and 8 for olaparib and abiraterone.

Part A Pharmacokinetics (PK): Olaparib Maximum Plasma Concentration at Steady State (Cmax,ss)

"Following multiple dosing to steady state of olaparib 300 mg bid, the Cohort 2 olaparib Cmax,ss is presented for olaparib monotherapy and for olaparib given in combination with abiraterone.~Only patients with data available for analysis at each time point are presented." (NCT01972217)
Timeframe: PK sampling for Cohort 2 Group 1 was between Days 3 and 7 for olaparib, and Days 4 and 8 for olaparib and abiraterone. PK sampling for Cohort 2 Group 2 was between Days 5 and 7 for abiraterone, and Days 6 and 8 for olaparib and abiraterone.

Part A PK Analysis: Olaparib Area Under the Plasma Concentration-Time Curve at Steady State (AUCss)

"Following multiple dosing to steady state of olaparib 300 mg bid, the Cohort 2 olaparib AUCss is presented for olaparib monotherapy and for olaparib given in combination with abiraterone.~Only patients with data available for analysis at each time point are presented." (NCT01972217)
Timeframe: PK sampling for Cohort 2 Group 1 was between Days 3 and 7 for olaparib, and Days 4 and 8 for olaparib and abiraterone. PK sampling for Cohort 2 Group 2 was between Days 5 and 7 for abiraterone, and Days 6 and 8 for olaparib and abiraterone.

Part A PK Analysis: Olaparib Area Under the Plasma Concentration-Time Curve at Steady State (AUCss)

"Following multiple dosing to steady state of olaparib 300 mg bid, the Cohort 2 olaparib AUCss is presented for olaparib monotherapy and for olaparib given in combination with abiraterone.~Only patients with data available for analysis at each time point are presented." (NCT01972217)
Timeframe: PK sampling for Cohort 2 Group 1 was between Days 3 and 7 for olaparib, and Days 4 and 8 for olaparib and abiraterone. PK sampling for Cohort 2 Group 2 was between Days 5 and 7 for abiraterone, and Days 6 and 8 for olaparib and abiraterone.

Part A PK Analysis: Olaparib Minimum Plasma Concentration at Steady State (Cmin,ss)

"Following multiple dosing to steady state of olaparib 300 mg bid, the Cohort 2 olaparib Cmin,ss is presented for olaparib monotherapy and for olaparib given in combination with abiraterone.~Only patients with data available for analysis at each time point are presented." (NCT01972217)
Timeframe: PK sampling for Cohort 2 Group 1 was between Days 3 and 7 for olaparib, and Days 4 and 8 for olaparib and abiraterone. PK sampling for Cohort 2 Group 2 was between Days 5 and 7 for abiraterone, and Days 6 and 8 for olaparib and abiraterone.

Part A PK Analysis: Olaparib Minimum Plasma Concentration at Steady State (Cmin,ss)

"Following multiple dosing to steady state of olaparib 300 mg bid, the Cohort 2 olaparib Cmin,ss is presented for olaparib monotherapy and for olaparib given in combination with abiraterone.~Only patients with data available for analysis at each time point are presented." (NCT01972217)
Timeframe: PK sampling for Cohort 2 Group 1 was between Days 3 and 7 for olaparib, and Days 4 and 8 for olaparib and abiraterone. PK sampling for Cohort 2 Group 2 was between Days 5 and 7 for abiraterone, and Days 6 and 8 for olaparib and abiraterone.

Part A PK Analysis: Olaparib Time to Reach Maximum Plasma Concentration at Steady State (Tmax,ss)

"Following multiple dosing to steady state of olaparib 300 mg bid, the Cohort 2 olaparib tmax,ss is presented for olaparib monotherapy and for olaparib given in combination with abiraterone.~Only patients with data available for analysis at each time point are presented." (NCT01972217)
Timeframe: PK sampling for Cohort 2 Group 1 was between Days 3 and 7 for olaparib, and Days 4 and 8 for olaparib and abiraterone. PK sampling for Cohort 2 Group 2 was between Days 5 and 7 for abiraterone, and Days 6 and 8 for olaparib and abiraterone.

Part A PK Analysis: Olaparib Time to Reach Maximum Plasma Concentration at Steady State (Tmax,ss)

"Following multiple dosing to steady state of olaparib 300 mg bid, the Cohort 2 olaparib tmax,ss is presented for olaparib monotherapy and for olaparib given in combination with abiraterone.~Only patients with data available for analysis at each time point are presented." (NCT01972217)
Timeframe: PK sampling for Cohort 2 Group 1 was between Days 3 and 7 for olaparib, and Days 4 and 8 for olaparib and abiraterone. PK sampling for Cohort 2 Group 2 was between Days 5 and 7 for abiraterone, and Days 6 and 8 for olaparib and abiraterone.

Part A PK: Abiraterone AUCss

"Following multiple dosing to steady state of abiraterone 1000 mg once daily, the Cohort 2 abiraterone AUCss is presented for abiraterone monotherapy and for olaparib given in combination with abiraterone.~Only patients with data available for analysis at each time point are presented." (NCT01972217)
Timeframe: PK sampling for Cohort 2 Group 1 was between Days 3 and 7 for olaparib, and Days 4 and 8 for olaparib and abiraterone. PK sampling for Cohort 2 Group 2 was between Days 5 and 7 for abiraterone, and Days 6 and 8 for olaparib and abiraterone.

Part A PK: Abiraterone AUCss

"Following multiple dosing to steady state of abiraterone 1000 mg once daily, the Cohort 2 abiraterone AUCss is presented for abiraterone monotherapy and for olaparib given in combination with abiraterone.~Only patients with data available for analysis at each time point are presented." (NCT01972217)
Timeframe: PK sampling for Cohort 2 Group 1 was between Days 3 and 7 for olaparib, and Days 4 and 8 for olaparib and abiraterone. PK sampling for Cohort 2 Group 2 was between Days 5 and 7 for abiraterone, and Days 6 and 8 for olaparib and abiraterone.

Part A PK: Abiraterone Cmax,ss

"Following multiple dosing to steady state of abiraterone 1000 mg once daily, the Cohort 2 abiraterone Cmax,ss is presented for abiraterone monotherapy and for olaparib given in combination with abiraterone.~Only patients with data available for analysis at each time point are presented." (NCT01972217)
Timeframe: PK sampling for Cohort 2 Group 1 was between Days 3 and 7 for olaparib, and Days 4 and 8 for olaparib and abiraterone. PK sampling for Cohort 2 Group 2 was between Days 5 and 7 for abiraterone, and Days 6 and 8 for olaparib and abiraterone.

Part A PK: Abiraterone Cmax,ss

"Following multiple dosing to steady state of abiraterone 1000 mg once daily, the Cohort 2 abiraterone Cmax,ss is presented for abiraterone monotherapy and for olaparib given in combination with abiraterone.~Only patients with data available for analysis at each time point are presented." (NCT01972217)
Timeframe: PK sampling for Cohort 2 Group 1 was between Days 3 and 7 for olaparib, and Days 4 and 8 for olaparib and abiraterone. PK sampling for Cohort 2 Group 2 was between Days 5 and 7 for abiraterone, and Days 6 and 8 for olaparib and abiraterone.

Part A PK: Abiraterone Cmin,ss

"Following multiple dosing to steady state of abiraterone 1000 mg once daily, the Cohort 2 abiraterone Cmin,ss is presented for abiraterone monotherapy and for olaparib given in combination with abiraterone.~Only patients with data available for analysis at each time point are presented." (NCT01972217)
Timeframe: PK sampling for Cohort 2 Group 1 was between Days 3 and 7 for olaparib, and Days 4 and 8 for olaparib and abiraterone. PK sampling for Cohort 2 Group 2 was between Days 5 and 7 for abiraterone, and Days 6 and 8 for olaparib and abiraterone.

Part A PK: Abiraterone Cmin,ss

"Following multiple dosing to steady state of abiraterone 1000 mg once daily, the Cohort 2 abiraterone Cmin,ss is presented for abiraterone monotherapy and for olaparib given in combination with abiraterone.~Only patients with data available for analysis at each time point are presented." (NCT01972217)
Timeframe: PK sampling for Cohort 2 Group 1 was between Days 3 and 7 for olaparib, and Days 4 and 8 for olaparib and abiraterone. PK sampling for Cohort 2 Group 2 was between Days 5 and 7 for abiraterone, and Days 6 and 8 for olaparib and abiraterone.

Part A PK: Abiraterone Tmax,ss

"Following multiple dosing to steady state of abiraterone 1000 mg once daily, the Cohort 2 abiraterone tmax,ss is presented for abiraterone monotherapy and for olaparib given in combination with abiraterone.~Only patients with data available for analysis at each time point are presented." (NCT01972217)
Timeframe: PK sampling for Cohort 2 Group 1 was between Days 3 and 7 for olaparib, and Days 4 and 8 for olaparib and abiraterone. PK sampling for Cohort 2 Group 2 was between Days 5 and 7 for abiraterone, and Days 6 and 8 for olaparib and abiraterone.

Part A PK: Abiraterone Tmax,ss

"Following multiple dosing to steady state of abiraterone 1000 mg once daily, the Cohort 2 abiraterone tmax,ss is presented for abiraterone monotherapy and for olaparib given in combination with abiraterone.~Only patients with data available for analysis at each time point are presented." (NCT01972217)
Timeframe: PK sampling for Cohort 2 Group 1 was between Days 3 and 7 for olaparib, and Days 4 and 8 for olaparib and abiraterone. PK sampling for Cohort 2 Group 2 was between Days 5 and 7 for abiraterone, and Days 6 and 8 for olaparib and abiraterone.

Part A: Percentage of Patients Experiencing Adverse Events (AEs)

"The safety and tolerability of olaparib in combination with abiraterone was assessed during Part A of the study. The percentage of patients experiencing AEs, including information on seriousness, severity, study treatment relationship and those leading to discontinuation for all doses of olaparib and for abiraterone are presented.~Severity of AEs was assessed using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse events (CTCAE) v4.0. AEs were assigned to a Grade from 1 through 5 as follows:~Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe or medically significant but not immediately life-threatening requiring hospitalisation; Grade 4: Life-threatening consequences; Grade 5: Death related to AE.~'c-r' = causally related 'discont' = discontinuation." (NCT01972217)
Timeframe: Cohort 1 and 2: From baseline in Part A (Day 1 for each cohort) up to 30 days following last dose of study treatment.

Part B: Percentage of Patients Experiencing AEs

"The safety and tolerability of olaparib when given in combination with abiraterone was assessed during Part B of the study. The percentage of patients experiencing AEs, including information on seriousness, severity, study treatment relationship and those leading to discontinuation for all doses of olaparib and for abiraterone are presented.~Severity of AEs was assessed using the NCI Common Terminology CTCAE v4.0. AEs were assigned to a Grade from 1 through 5 as follows:~Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe or medically significant but not immediately life-threatening requiring hospitalisation; Grade 4: Life-threatening consequences; Grade 5: Death related to AE.~'c-r' = causally related. 'discont' = discontinuation. 'ola/pla' = olaparib/placebo." (NCT01972217)
Timeframe: From first dose of study treatment following randomisation in Part B up to 30 days following last dose of study treatment (up to approximately 3 years).

Part B: Percentage of Patients With PSA Responses

"The percentages of patients with single visit responses and with confirmed responses are presented to assess the anti-tumour activity of olaparib when given in addition to abiraterone, compared with placebo given in addition to abiraterone.~A single visit response was defined as any post-dose visit PSA level reduced by 50% or more compared with baseline.~A confirmed response was defined as a reduction in PSA level of 50% or more on 2 consecutive occasions at least 4 weeks apart compared with baseline.~Patients may have had more than 1 single visit response or confirmed response but were counted once." (NCT01972217)
Timeframe: From baseline, then every 4 weeks up to Week 24, and then every 12 weeks.

Objective Response Rate (ORR)

ORR, defined as the best overall radiographic response after randomization (Period 2 Week 1) as per Investigator assessments of response for soft tissue disease per RECIST 1.1, in participants who had a measurable tumor. ORR was reported as the percentage of participants with complete response (CR) or partial response (PR). CR was defined as disappearance of all target and nontarget lesions. Any pathological lymph nodes (whether target or nontarget) must have reduction in short axis to < 10 mm from baseline measurement. PR was defined as at least a 30% decrease in the sum of diameters (longest for nonnodal lesions, short axis for nodal lesions) of target lesions taking as reference to the baseline sum of diameters. (NCT02288247)
Timeframe: From date of randomization up to median duration of 35 weeks

Progression Free Survival (PFS)

PFS: time from randomization (Period 2 Week 1) to earliest progression event. Progression is defined as radiographic progression, unequivocal clinical progression, or death on study. Radiographic progression is defined for bone disease by appearance of ≥ 2 new lesions on whole-body radionuclide bone scan per Prostate Cancer Clinical Trials Working Group 2 (PCWG2) criteria (i.e., unconfirmed progressive disease) that needs to be confirmed in the next assessment (i.e., progressive disease in the next assessment) or for soft tissue disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Unequivocal clinical progression is defined as new onset cancer pain requiring chronic administration of opiate analgesia or deterioration from prostate cancer of Eastern Cooperative Oncology Group (ECOG) performance status score to ≥ 3, or initiation of subsequent lines of cytotoxic chemotherapy or radiation therapy or surgical intervention due to complications of tumor progression. (NCT02288247)
Timeframe: From date of randomization to the earliest of either documented disease progression (median duration: 35 weeks)

Time to First Skeletal-related Event (SRE)

Time to first SRE, defined as the time from randomization (Period 2 Week 1) to radiation therapy or surgery to bone, pathologic bone fracture, spinal cord compression, or change of antineoplastic therapy to treat bone pain. (NCT02288247)
Timeframe: From date of randomization up to median duration of 35 weeks

Time to Prostate-specific Antigen (PSA) Progression

Time to PSA progression, defined as the time from randomization (Period 2 Week 1) to the date of the first PSA value in Period 2 demonstrating progression (Period 2). The PSA progression date is defined as the date that a ≥ 25% increase and an absolute increase of ≥ 2 ng/mL above the nadir recorded in Period 2 is documented, which must be confirmed by a second consecutive value obtained at least 3 weeks later. (NCT02288247)
Timeframe: From date of randomization to the first PSA value (median duration: 35 weeks)

Change From Baseline in EuroQOL 5-dimension 5-level Questionnaire [EQ-5D-5L] Visual Analog Scale (VAS)

The EQ-5D-5L VAS records the participant's self-rated health on a vertical visual analogue scale, where the endpoints are labelled from 0 (worst health imaginable) to 100 (best health imaginable). (NCT02288247)
Timeframe: Period 2: Baseline, weeks 1, 13, 25, 37, 49, 61, 73, 85, 97, 109, 121, 133, 145, 157, 169, 181

Change From Baseline in EuroQOL 5-dimension 5-level Questionnaire [EQ-5D-5L] Visual Analog Scale (VAS)

The EQ-5D-5L VAS records the participant's self-rated health on a vertical visual analogue scale, where the endpoints are labelled from 0 (worst health imaginable) to 100 (best health imaginable). (NCT02288247)
Timeframe: Period 2: Baseline, weeks 1, 13, 25, 37, 49, 61, 73, 85, 97, 109, 121, 133, 145, 157, 169, 181

Change From Baseline in Functional Assessment of Cancer Therapy - Prostate (FACT-P)

FACT-P quality of life questionnaire is a multi-dimensional, self-reported quality of life instrument specifically designed for use with prostate cancer participants. It consists of 27 core items which assess participant function in four domains rated on 0 to 4 Likert-type scale: physical well-being (PWB) (7 items; 0 [worst] to 4 [better], score range 0-28), social/family well-being (SWB) (7 items; 0 [worst] to 4 [better], score range 0-28), emotional well-being (EWB) (6 items; 0 [worst] to 4 [better], score range 0-24), and functional well-being (FWB) (7 items; 0 [worst] to 4 [better], score range 0-28), which is further supplemented by 12 site-specific items to assess for prostate-related symptoms (Prostate Cancer Subscale [PCS] 12 items rated on Likert-type scale 0 [worst] to 4 [better], score range 0-48). The total domain scores and PCS subscale score are then combined to a global quality of life score ranging between 0 to 156; higher scores representing better quality of life. (NCT02288247)
Timeframe: Period 2: Baseline, weeks 1, 13, 25, 37, 49, 61, 73, 85, 97, 109, 121, 133, 145, 157, 169, 181

Change From Baseline in Functional Assessment of Cancer Therapy - Prostate (FACT-P)

FACT-P quality of life questionnaire is a multi-dimensional, self-reported quality of life instrument specifically designed for use with prostate cancer participants. It consists of 27 core items which assess participant function in four domains rated on 0 to 4 Likert-type scale: physical well-being (PWB) (7 items; 0 [worst] to 4 [better], score range 0-28), social/family well-being (SWB) (7 items; 0 [worst] to 4 [better], score range 0-28), emotional well-being (EWB) (6 items; 0 [worst] to 4 [better], score range 0-24), and functional well-being (FWB) (7 items; 0 [worst] to 4 [better], score range 0-28), which is further supplemented by 12 site-specific items to assess for prostate-related symptoms (Prostate Cancer Subscale [PCS] 12 items rated on Likert-type scale 0 [worst] to 4 [better], score range 0-48). The total domain scores and PCS subscale score are then combined to a global quality of life score ranging between 0 to 156; higher scores representing better quality of life. (NCT02288247)
Timeframe: Period 2: Baseline, weeks 1, 13, 25, 37, 49, 61, 73, 85, 97, 109, 121, 133, 145, 157, 169, 181

Prostate-specific Antigen (PSA) Response

PSA response, defined as a decrease in percentage change from randomization (Period 2 Week 1) of 50% or more. PSA response was derived at Week 13 and at any time after randomization in Period 2. PSA response at any time is defined as a decrease in percentage change from randomization (Period 2 Week 1) at any time after randomization of 50% or more. Percentage of participants with PSA response was reported. (NCT02288247)
Timeframe: Randomization, Week 13, any time after randomization in Period 2 (median of 35 weeks)

Number of Participants With Any Treatment-emergent Additional Primary Malignancies

Treatment-emergent additional primary malignancies were adverse events identified as additional primary malignancies that occurred after start of study treatment until the end of the treatment period. (NCT02043678)
Timeframe: From start of study treatment until 4 weeks after last study treatment, up to 65 months

Number of Participants With Treatment-emergent Bone Fractures

Treatment-emergent fractures were adverse events identified as fractures that occurred after start of study treatment until the end of the treatment period. All bone fractures and bone-associated events (e.g., osteoporosis) were reported as either AEs, or SAEs if the criteria of SAE were met, regardless of the investigator's causality assessment. (NCT02043678)
Timeframe: From start of study treatment until 4 weeks after last study treatment, up to 65 months

Overall Survival (OS)

OS was defined as the time (months) from the date of randomization to the date of death due to any cause. Subjects alive at the survival cut-off date were censored at the last date known to be alive. (NCT02043678)
Timeframe: From randomization until death from any cause, up to 67 months

Radiological Progression Free Survival (rPFS)

rPFS was defined as the time (months) from the date of randomization to the date of confirmed radiological progression or death (if death occurred before progression) based on independent assessment. (NCT02043678)
Timeframe: From randomization until the date of confirmed radiological progression or death, up to 47 months

Symptomatic Skeletal Event Free Survival (SSE-FS)

SSE-FS was defined as time (months) from randomization to the earliest of onset date of skeletal symptoms treated with external beam radiotherapy (EBRT), onset date of pathological bone fracture, onset date of spinal cord compression, procedure date of tumor-related orthopedic surgery, or death from any cause. Subjects who died without prior SSE and ≥ 13 weeks after the last SSE assessment are censored at the last SSE assessment date. Subjects alive at the survival cut-off date are censored at the last date known to be alive. Subjects with multiple events are only counted for the category in which the first event occurred. If multiple SSE (component events) occur on the same date for 1 subject, the subject is only counted into 1 category in the order of: spinal cord compression > bone fracture > orthopedic surgery > EBRT. (NCT02043678)
Timeframe: From randomization until first onset of on-study symptomatic skeletal event (SSE) or death, up to 47 months

Time to Cytotoxic Chemotherapy

Time to cytotoxic chemotherapy is time (months) from randomization to the earliest date of the first cytotoxic chemotherapy. Participants who have not started cytotoxic chemotherapy during the study were censored at the last assessment date. (NCT02043678)
Timeframe: From randomization until the date of first cytotoxic chemotherapy, up to 47 months

Time to Opiate Use for Cancer Pain

Time to opiate use for cancer pain was defined as the interval from the date of randomization to the date of opiate use. (NCT02043678)
Timeframe: From randomization until the date of opiate use, up to 47 months

Time to Pain Progression

Time to pain progression was defined as the interval from randomization to the first date a subject experienced pain progression, assessed by BPI-SF (see Baseline Characteristics) and defined as: an increase of 2 or more points in the average worst pain score (WPS) from baseline observed at 2 consecutive evaluations >= 4 weeks apart or initiation of short- or long-acting opioid use for pain for subjects with WPS 0 at baseline; an increase of 2 or more points in the average WPS from baseline observed at 2 consecutive evaluations ≥ 4 weeks apart and an average WPS of ≥ 4 OR initiation of short- or long-acting opioid use for pain for subjects with WPS 1 to 3 at baseline. Subjects without pain progression at the end of study are censored at the last date known to have not progressed: the last evaluation date for pain scores or last visit when recorded opiate use, whichever is last. Subjects with no on-study assessment or no baseline assessment are censored at the date of randomization. (NCT02043678)
Timeframe: From randomization until the date of pain progression based on pain score, up to 47 months

Number of Participants With Any Study Drug-related Post-treatment Adverse Events Per Maximum Intensity

"An adverse event (AE) was any untoward medical occurrence (i.e., any unfavorable and unintended sign [including abnormal laboratory findings], symptom or disease) in a participant in the study. Any bleeding event occurring during the study was not documented as an AE because this event was planned to be captured in the assessment of efficacy. AEs that started after the treatment period were defined as post-treatment AEs. Drug-related AEs were those with reasonable causal relationship to the study treatment decided by the investigators." (NCT02043678)
Timeframe: After the treatment period, up to 46 months

Number of Participants With Post-treatment Adverse Events

"An adverse event (AE) was any untoward medical occurrence (i.e., any unfavorable and unintended sign [including abnormal laboratory findings], symptom or disease) in a participant in the study. Any bleeding event occurring during the study was not documented as an AE because this event was planned to be captured in the assessment of efficacy. AEs that started after the treatment period were defined as post-treatment AEs. Drug-related AEs were those with reasonable causal relationship to the study treatment decided by the investigators." (NCT02043678)
Timeframe: After the treatment period, up to 46 months

Number of Participants With Post-treatment Bone Fractures

Post-treatment fractures were adverse events identified as fractures that occured after the end of the treatment period until participant died, was lost to follow-up, withdrew informed consent, actively objected to collection of further data, or was transitioned to the extended safety follow-up study. All bone fractures and bone-associated events (e.g., osteoporosis), were reported as either AEs, or SAEs if the criteria of SAE were met, regardless of the investigator's causality assessment. (NCT02043678)
Timeframe: After the treatment period, up to 46 months

Number of Participants With Post-treatment Chemotherapy-related Blood and Lymphatic System Disorders

Post-treatment blood and lymphatic system disorders were adverse events identified as blood and lymphatic system disorders that occurred after the end of the treatment period until participant died, was lost to follow-up, withdrew informed consent, actively objected to collection of further data, or was transitioned to the extended safety follow-up study. (NCT02043678)
Timeframe: After the treatment period, up to 46 months

Number of Participants With Treatment-emergent Adverse Events

"An adverse event (AE) was any untoward medical occurrence (i.e., any unfavorable and unintended sign [including abnormal laboratory findings], symptom or disease) in a participant in the study. A serious adverse event (SAE) was any untoward medical occurrence that at any dose was resulting in death, was lifethreatening, requires hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity. AEs or SAEs occurring after start of study treatment until the end of the treatment period were defined as treatment-emergent AEs (TEAEs) or serious TEAEs. Drug-related TEAEs or serious TEAEs were those with reasonable causal relationship to the study treatment decided by the investigators." (NCT02043678)
Timeframe: From start of study treatment until the end of the treatment period, up to 65 months

Number of Subjects With Radium-223/Placebo-related Treatment-emergent Adverse Events Per Maximum Intensity

"An adverse event (AE) was any untoward medical occurrence (i.e., any unfavorable and unintended sign [including abnormal laboratory findings], symptom or disease) in a participant in the study. A serious adverse event (SAE) was any untoward medical occurrence that at any dose was resulting in death, was lifethreatening, requires hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity. AEs or SAEs occurring after start of study treatment until the end of the treatment period were defined as treatment-emergent AEs (TEAEs) or serious TEAEs. Radium-223/placebo-related TEAEs or serious TEAEs were those with reasonable causal relationship to radium-223 or placebo decided by the investigators." (NCT02043678)
Timeframe: From start of study treatment until the end of the treatment period, up to 65 months

"Time to Pain Progression (TTPP) as Assessed by Brief Pain Inventory-Short Form (BPI-SF) Item 3 (Worst Pain in 24 Hours) and Opiate Analgesic Use Assessed by the Analgesic Quantification Algorithm [AQA] Score"

"TTPP was defined as the time from randomization to pain progression as determined by Item 3 of the BPI-SF and by the AQA score. Pain progression was defined as:~For participants asymptomatic at baseline: a ≥2-point change from baseline in the average (4-7 days) BPI-SF item 3 score at 2 consecutive visits OR initiation of opioid use for pain~For participants symptomatic at baseline (average BPI-SF Item 3 score >0 and/or currently taking opioids:, a ≥2-point change from baseline in the average BPI-SF Item 3 score and an average worst pain score ≥4 and no decrease in average opioid use (≥1-point decrease in AQA score from a starting value of 2 or higher) OR any increase in opioid use at 2 consecutive follow-up visits.~TTPP was calculated using the product-limit (Kaplan-Meier) method for censored data. Participants who had > 2 consecutive visits that were not evaluable for pain progression were censored at the last evaluable assessment." (NCT03834506)
Timeframe: Up to 36.5 months

Duration of Response (DOR) Per Prostate Cancer Working Group (PCWG)-Modified Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review

DOR was defined as the time from first documented evidence of complete response (CR) or partial response (PR) per PCWG and RECIST 1.1 criteria until progressive disease (PD) or death. PD per RECIST 1.1 was defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. PD per PCWG was the appearance of ≥2 new bone lesions on bone scan, that have been confirmed to not represent tumor flare, and were persistent for ≥6 weeks. The DOR was calculated using the product-limit (Kaplan-Meier) method for censored data. If a participant had not progressed, the participant was censored at the date of last disease assessment. (NCT03834506)
Timeframe: Up to 36.5 months

Number of Participants Who Discontinued Study Treatment Due To an Adverse Event (AE)

An AE was any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE could therefore have been any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The number of participants who discontinued study treatment due to an AE is presented. (NCT03834506)
Timeframe: Up to approximately 27 months

Number of Participants Who Experienced an Adverse Event (AE)

An AE was any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE could therefore have been any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The number of participants who experienced an AE is presented. (NCT03834506)
Timeframe: Up to approximately 30 months

Objective Response Rate (ORR) Per Prostate Cancer Working Group (PCWG)-Modified Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review

ORR was defined as the percentage of participants with complete response (CR: disappearance of all target lesions per RECIST 1.1; and no evidence of disease (NED) on bone scan per PCWG) or partial response (PR: at least a 30% decrease in the sum of diameters of target lesions per RECIST 1.1; and non-progressive disease, non-evaluable [NE], or NED on bone scan or CR with non-progressive disease or NE bone scan per PCWG). (NCT03834506)
Timeframe: Up to 36.5 months

Overall Survival (OS)

OS was defined as the time from randomization to death due to any cause. The OS was calculated using the product-limit (Kaplan-Meier) method for censored data. Participants without documented death at the time of the analysis were censored at the date of the last follow-up. (NCT03834506)
Timeframe: Up to 36.5 months

Prostate-specific Antigen (PSA) Response Rate

The Prostate-specific Antigen (PSA) response rate was the percentage of participants who had PSA response defined as a reduction in the PSA level from baseline by ≥50%. The reduction in PSA level was confirmed by an additional PSA evaluation performed ≥3 weeks from the original response. The analysis was performed on participants who had baseline PSA measurements. (NCT03834506)
Timeframe: Up to 36.5 months

Radiographic Progression-free Survival (rPFS) Per Prostate Cancer Working Group (PCWG)-Modified Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR)

rPFS was defined as the time from randomization to occurrence of: radiological tumor progression using RECIST 1.1 as assessed by BICR; progression of bone lesions using PCWG criteria; or death due to any cause. Progression as per RECIST 1.1 was ≥20% increase in sum of diameters of target lesions and progression of existing non-target lesions. Progression of bone lesions by PCWG criteria was the appearance of ≥2 new bone lesions on bone scan, that have been confirmed to not represent tumor flare, and was persistent for ≥6 weeks. The rPFS was calculated using the product-limit (Kaplan-Meier) method for censored data. Participants without a rPFS event were censored at the date of last disease assessment. (NCT03834506)
Timeframe: Up to approximately 28 months

Time to First Symptomatic Skeletal-related Event (SSRE)

"SSRE was the time from randomization to the first symptomatic skeletal-related event defined as:~Use of external-beam radiation therapy (EBRT) to prevent or relieve skeletal symptoms~Occurrence of new symptomatic pathologic bone fracture (vertebral or non-vertebral)~Occurrence of spinal cord compression~Tumor-related orthopedic surgical intervention, whichever occurs first.~The SSRE was calculated using the product-limit (Kaplan-Meier) method for censored data. Participants without symptomatic skeletal-related events were censored at the last evaluable assessment." (NCT03834506)
Timeframe: Up to 36.5 months

Time to Initiation of the First Subsequent Anti-cancer Therapy (TFST)

TFST was defined as the time from randomization to initiation of the first subsequent anti-cancer therapy or death; whichever occurred first. The TFST was calculated using the product-limit (Kaplan-Meier) method for censored data. Any participant not known to have further subsequent therapy or death was censored at the last known time that no subsequent new anti-cancer therapy was received. (NCT03834506)
Timeframe: Up to approximately 28 months

Time to Prostate-specific Antigen (PSA) Progression

"The time to PSA progression was the time from randomization to PSA progression. The PSA progression date was defined as the date of:~≥25% increase and ≥2 ng/mL above the nadir, confirmed by a second value ≥3 weeks later if there was PSA decline from baseline; OR~≥25% increase and ≥2 ng/mL increase from baseline beyond 12 weeks if there was no PSA decline from baseline~Time to PSA progression was calculated using the product-limit (Kaplan-Meier) method for censored data. Participants without PSA progression were censored at the last evaluable assessment." (NCT03834506)
Timeframe: Up to 36.5 months

Time to Radiographic Soft Tissue Progression Per Soft Tissue Rules of Prostate Cancer Working Group (PCWG)-Modified Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR)

The time to radiographic soft tissue progression was defined as the time from randomization to radiographic soft tissue progression per soft tissue rules of PCWG-modified RECIST 1.1 as assessed by BICR. Progression was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered progression. Time to radiographic soft tissue progression was calculated using the product-limit (Kaplan-Meier) method for censored data. Participants without radiographic soft tissue progression were censored at the last evaluable assessment. (NCT03834506)
Timeframe: Up to 36.5 months

Investigator-Assessed Radiographic Progression-Free Survival (rPFS) Per PCWG3 Criteria (Intent-To-Treat (ITT) Population)

Radiographic progression-free survival is defined as time from date of randomization to the first occurrence of documented disease progression, as assessed by the investigator with use of the Prostate Cancer Working Group 3 (PCWG3) criteria or death from any cause, whichever occurs first. Disease progression for soft tissue is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm in the sum of diameters of target lesions; progression of non target lesions; the appearance of one or more new lesions. Disease progression for bone lesions is defined as 2 or more new lesions compared to baseline followed by a confirmatory bone scan at least 6 weeks later. rPFS will be analyzed in the Intent-to-Treat (ITT) population. (NCT03072238)
Timeframe: Up to approximately 31 months

Investigator-Assessed Radiographic Progression-Free Survival (rPFS) Per PCWG3 Criteria (PTEN Loss Population)

Radiographic progression-free survival is defined as time from date of randomization to the first occurrence of documented disease progression, as assessed by the investigator with use of the Prostate Cancer Working Group 3 (PCWG3) criteria or death from any cause, whichever occurs first. Disease progression for soft tissue is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm in the sum of diameters of target lesions; progression of non target lesions; the appearance of one or more new lesions. Disease progression for bone lesions is defined as 2 or more new lesions compared to baseline followed by a confirmatory bone scan at least 6 weeks later. rPFS will be analyzed in participants with phosphatase and tensin homolog (PTEN) - loss tumors (using the Ventana PTEN immunohistochemistry (IHC) assay). (NCT03072238)
Timeframe: Up to approximately 31 months

Plasma Concentrations of Abiraterone at Specified Timepoints

Plasma samples for pharmacokinetic characterization was collected at various timepoints in all participants. (NCT03072238)
Timeframe: Pre-dose at steady state in Cycle 1, Day 15 and Cycle 3 Day 1 (each cycle length= 28 days)

Plasma Concentrations of Ipatasertib at Specified Timepoints

Plasma samples for pharmacokinetic characterization was collected at various timepoints in all participants. (NCT03072238)
Timeframe: 1-3 hours post-dose (Cycle 1, Day 1; Cycle 1 Day 15 and Cycle 3 Day 1) and pre-dose at steady state (Cycle 1 Day 15, Cycle 3 Day 1, Cycle 6 Day 1) (each cycle length= 28 days)

Reviews

6 reviews available for prednisolone and Androgen-Independent Prostatic Cancer

Trials

23 trials available for prednisolone and Androgen-Independent Prostatic Cancer

Other Studies

34 other studies available for prednisolone and Androgen-Independent Prostatic Cancer