ipi-926 and Neoplasms

ipi-926 has been researched along with Neoplasms* in 2 studies

Reviews

1 review(s) available for ipi-926 and Neoplasms

ArticleYear
Targeting the hedgehog pathway: the development of cyclopamine and the development of anti-cancer drugs targeting the hedgehog pathway.
    Mini reviews in medicinal chemistry, 2011, Volume: 11, Issue:3

    The Hedgehog signalling pathway plays a critical role in controlling growth, especially during development, but is often over-activated in tumourigenesis. It has recently emerged as an important target for anticancer drugs, with several compounds in clinical trials. This review initially describes the Hedgehog pathway, focussing on the Patched receptor, and the Smoothened GPCR-like protein, as well as discussing the role of Cancer Stem Cells. It subsequently presents the discovery and development of drugs targeting this pathway. The initial focus is on cyclopamine - the first compound discovered that could inhibit the Hedgehog pathway - and selected cyclopamine analogues, including a review of the development of IPI-926. In addition, a number of other compounds are briefly discussed, to give an overview of current therapies in clinical development, and to indicate the possibilities for targeting different parts of the Hedgehog pathway in future. Finally, combination chemotherapy - incorporating a Hedgehog pathway inhibitor as well as another drug - is discussed from the perspective of drug resistance and effects on cancer stem cells.

    Topics: Antineoplastic Agents; Hedgehog Proteins; Humans; Neoplasms; Neoplastic Stem Cells; Signal Transduction; Veratrum Alkaloids

2011

Trials

1 trial(s) available for ipi-926 and Neoplasms

ArticleYear
Phase I study of the Hedgehog pathway inhibitor IPI-926 in adult patients with solid tumors.
    Clinical cancer research : an official journal of the American Association for Cancer Research, 2013, May-15, Volume: 19, Issue:10

    To conduct a first-in-human phase I study to determine the dose-limiting toxicities (DLT), characterize the pharmacokinetic profile, and document the antitumor activity of IPI-926, a new chemical entity that inhibits the Hedgehog pathway (HhP).. Patients with solid tumors refractory to standard therapy were given IPI-926 once daily (QD) by mouth in 28-day cycles. The starting dose was 20 mg, and an accelerated titration schedule was used until standard 3 + 3 dose-escalation cohorts were implemented. Pharmacokinetics were evaluated on day -7 and day 22 of cycle 1.. Ninety-four patients (32F, 62M; ages, 39-87) received doses ranging from 20 to 210 mg QD. Dose levels up to and including 160 mg administered QD were well tolerated. Toxicities consisted of reversible elevations in aspartate aminotransferase (AST), alanine aminotransferase (ALT) and bilirubin, fatigue, nausea, alopecia, and muscle spasms. IPI-926 was not associated with hematologic toxicity. IPI-926 pharmacokinetics were characterized by a slow absorption (T(max) = 2-8 hours) and a terminal half-life (t(1/2)) between 20 and 40 hours, supporting QD dosing. Of those HhP inhibitor-naïve patients with basal cell carcinoma (BCC) who received more than one dose of IPI-926 and had a follow-up clinical or Response Evaluation Criteria in Solid Tumors (RECIST) assessment, nearly a third (8 of 28 patients) showed a response to IPI-926 at doses ≥130 mg.. IPI-926 was well tolerated up to 160 mg QD within 28-day cycles, which was established as the recommended phase II dose and schedule for this agent. Single-agent activity of IPI-926 was observed in HhP inhibitor-naïve patients with BCC.

    Topics: Adult; Aged; Aged, 80 and over; Alanine Transaminase; Alopecia; Area Under Curve; Aspartate Aminotransferases; Dose-Response Relationship, Drug; Drug Administration Schedule; Fatigue; Female; Follow-Up Studies; Hedgehog Proteins; Humans; Male; Metabolic Clearance Rate; Middle Aged; Nausea; Neoplasms; Signal Transduction; Spasm; Treatment Outcome; Veratrum Alkaloids

2013