NCT01096355

Gamma-Secretase Inhibitor RO4929097 in Treating Patients With Metastatic or Unresectable Solid Malignancies

A Phase I Study of Various Administration Schedules of RO4929097 With Multi-parameter Assessment (Biomarkers, Pharmacokinetics, Pharmacodynamics) in Patients With Advanced Solid Cancers

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 28 (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, best way to give, and best dose of gamma-secretase inhibitor RO4929097 in treating patients with metastatic or unresectable solid malignancies. Enzyme inhibitors, such as gamma-secretase inhibitor RO4929097, may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Detailed description

PRIMARY OBJECTIVES: I. To determine the safety profile of 6 different administration schedules of gamma-secretase inhibitor RO4929097 in patients with advanced solid malignancies. SECONDARY OBJECTIVES: I. To determine pharmacokinetic (PK) parameters of gamma-secretase inhibitor RO4929097 administered using 6 different administration schedules. II. To assess the preliminary antitumor activity of gamma-secretase inhibitor RO4929097 in these patients. TERTIARY OBJECTIVES: I. To assess the pharmacodynamic (PD) effects of gamma-secretase inhibitor RO4929097 on Notch signaling pathway in tumor and surrogate tissues, as well as soluble markers of angiogenesis in plasma, when administered using 6 different dosing schedules. (Exploratory) II. To evaluate the relationship between PK and PD effects in an attempt to define the optimal biological dosing schedule (OBDS) that can provide a sustained inhibition of Notch signaling pathway over time with a tolerable toxicity profile. (Exploratory) III. To correlate inhibition of Notch signaling pathway measured in tumor and surrogate tissues with preliminary antitumor activity and assess the potential clinical predictive value of OBDS as defined above. (Exploratory) IV. To assess the effect of the various pharmacogenomic polymorphisms of the cytochrome P450 pathway on PK and PD parameters. (Exploratory) OUTLINE: This is a multicenter, dose-escalation study. Patients are assigned to 1 of 6 dose schedules. GROUP A: Patients receive oral gamma-secretase inhibitor RO4929097 once daily on days 1-3 and 8-10. GROUP B: Patients receive oral RO4929097 once daily on days 1-7. GROUP C: Patients receive oral RO4929097 once daily on days 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, and 21. GROUP D: Patients receive oral RO4929097 once daily on days 1, 8, and 15. GROUP E: Patients receive oral RO4929097 once daily on days 1, 4, 8, 11, 15, and 18. GROUP F: Patients receive oral RO4929097 once daily days 1-5, 8-12, and 15-19. Treatment in all groups repeats every 3 weeks in the absence of disease progression or unacceptable toxicity. Patients undergo tumor biopsies at baseline and between days 15 and 22 in the first course of treatment. Plasma samples are collected periodically for pharmacokinetic, pharmacodynamic, and pharmacogenomic analysis and to assess levels of adipsin and markers of angiogenesis. After completion of study treatment, patients are followed up for 4 weeks.

Conditions

• Unspecified Adult Solid Tumor, Protocol Specific

Interventions

Type	Name	Description
DRUG	gamma-secretase/Notch signalling pathway inhibitor RO4929097
OTHER	diagnostic laboratory biomarker analysis
OTHER	pharmacogenomic studies
OTHER	pharmacological study

Timeline

• Start date: 2010-02-01
• Primary completion: 2012-07-01
• First posted: 2010-03-31
• Last updated: 2014-04-02

Locations

3 sites across 1 country: Canada