NCT01145456

Gamma-Secretase Inhibitor RO4929097 and Gemcitabine Hydrochloride in Treating Patients With Advanced Solid Tumors

A Phase I Study of R04929097 in Combination With Gemcitabine in Patients With Advanced Solid Tumors

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 18 (actual)
• Sponsor: National Cancer Institute (NCI) · NIH
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase I trial is studying the side effects and best dose of gamma-secretase inhibitor RO4929097 when given together with gemcitabine hydrochloride in treating patients with advanced solid tumors. Gamma-secretase inhibitor RO4929097 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as gemcitabine hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving gamma-secretase inhibitor RO4929097 together with gemcitabine hydrochloride may kill more tumor cells.

Detailed description

PRIMARY OBJECTIVES: I. To determine the safety profile and establish the maximum-tolerated dose and recommended phase II dose of gamma-secretase inhibitor RO4929097 in combination with gemcitabine hydrochloride in patients with advanced solid tumors. SECONDARY OBJECTIVES: I. To determine the pharmacokinetic profile of gamma-secretase inhibitor RO4929097 when given in combination with gemcitabine hydrochloride and to correlate the pharmacokinetic profile with toxicity and biological activity. II. To assess the antitumor activity of gamma-secretase inhibitor RO4929097 and gemcitabine hydrochloride in patients with advanced solid tumors. III. To correlate the expression of biomarkers of Notch signaling in archival tumor tissue with antitumor activity of gamma-secretase inhibitor RO4929097 in combination with gemcitabine hydrochloride. OUTLINE: This is a multicenter, dose-escalation study of gamma-secretase inhibitor RO4929097. Patients receive oral gamma-secretase inhibitor RO4929097 once daily on days 1-3, 8-10, 15-17, and 22-24 and gemcitabine hydrochloride IV over 30 minutes on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Plasma and blood samples may be collected periodically for pharmacokinetic studies and biomarker analysis. After completion of study treatment, patients are followed up every 1 month for up to 1 year.

Conditions

• Adenocarcinoma of the Pancreas
• Recurrent Pancreatic Cancer
• Stage III Pancreatic Cancer
• Stage IV Pancreatic Cancer
• Unspecified Adult Solid Tumor, Protocol Specific

Interventions

Type	Name	Description
DRUG	gamma-secretase/Notch signalling pathway inhibitor RO4929097	Given orally
DRUG	gemcitabine hydrochloride	Given IV
OTHER	pharmacological study	Correlative studies
OTHER	laboratory biomarker analysis	Correlative studies

Timeline

• Start date: 2010-06-01
• Primary completion: 2013-11-01
• First posted: 2010-06-16
• Last updated: 2014-02-24

Locations

2 sites across 1 country: Canada