NCT01198184

Gamma-Secretase/Notch Signalling Pathway Inhibitor RO4929097 and Temsirolimus in Treating Patients With Advanced Solid Tumors

Safety and Efficacy of RO4929097 in Combination With Temsirolimus: A Pharmacokinetic and Pharmacodynamic Phase I Study in Patients With Advanced Solid Tumours With an Expansion of Cohort With Patients With Recurrent/Metastatic Endometrial and Renal Cell Cancers

• 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 giving gamma-secretase/Notch signalling pathway inhibitor RO4929097 and temsirolimus together in treating patients with advanced solid tumors. Gamma-secretase/Notch signalling pathway inhibitor RO4929097 and temsirolimus 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 recommended phase II dose (RP2D) and safety profile of temsirolimus in combination with RO4929097 (gamma-secretase/Notch signalling pathway inhibitor RO4929097) in patients with advanced solid tumors. SECONDARY OBJECTIVES: I. To obtain pharmacokinetic (PK) profiles for both drugs when administered in combination in order to quantify the expected interactive effects in PK between these two agents. II. To evaluate pharmacodynamic (PD) effects of both drugs when administered in combination, with the goal of identifying potential predictive and PD markers that need further exploration and validation in future trials. OUTLINE: This is a multicenter, dose-escalation study. Patients receive temsirolimus IV over 30 minutes on day -6 (course 1 only). Patients then receive temsirolimus IV or orally (PO) on days 1, 8, and 15 and gamma-secretase/Notch signalling pathway inhibitor RO4929097 PO once daily on days 1-3, 8-10, and 15-17. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Blood and tumor tissue samples may be collected periodically for pharmacokinetic and correlative analyses. After completion of study treatment, patients are followed up for 4 weeks.

Conditions

• Endometrial Papillary Serous Carcinoma
• Recurrent Endometrial Carcinoma
• Recurrent Renal Cell Cancer
• Stage III Endometrial Carcinoma
• Stage III Renal Cell Cancer
• Stage IV Endometrial Carcinoma
• Stage IV Renal Cell Cancer
• Unspecified Adult Solid Tumor, Protocol Specific

Interventions

Type	Name	Description
DRUG	temsirolimus	Given IV or PO
DRUG	gamma-secretase/Notch signalling pathway inhibitor RO4929097	Given PO
OTHER	laboratory biomarker analysis	Correlative studies
OTHER	pharmacological study	Correlative studies

Timeline

• Start date: 2010-08-01
• Primary completion: 2013-07-01
• Completion: 2013-10-01
• First posted: 2010-09-09
• Last updated: 2014-05-30

Locations

2 sites across 1 country: Canada