NCT01218620

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

Randomized Drug Interaction Study of RO4929097 for Advanced Solid Tumors

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 17 (actual)
• Sponsor: National Cancer Institute (NCI) · NIH
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This randomized phase I trial studies the side effects and best dose of RO4929097 in treating patients with advanced solid tumors. RO4929097 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Detailed description

PRIMARY OBJECTIVES: I. To evaluate the extent that RO4929097 induces its own metabolism using a 20mg dose on Regimen I and a 50mg dose on Regimen II by comparing Cycle 1 Day 1 and Day 10 plasma pharmacokinetic parameters. SECONDARY OBJECTIVES: I. To evaluate the effect of the strong inhibitor of CYP3A4, ketoconazole, on RO4929097 plasma pharmacokinetics. II. To evaluate the effect of the strong inducer of CYP3A4, 2D6 and 2C9, rifampin on RO4929097 plasma pharmacokinetics. III. To evaluate the effect of RO4929097 on the plasma pharmacokinetics of CYP450 substrates; midazolam (CYP3A4), omeprazole (CYP2C19), tolbutamide (CYP2C9) and dextromethorphan (CYP2D6) after single dose and chronic administration. IV. To assess the influence of polymorphisms in CYP3A4, 3A5, 2C9, ABCB1, and 2D6 on RO4929097 plasma pharmacokinetics V. To assess any evidence of clinical activity (CR, PR, SD) in patients with advanced solid tumors. OUTLINE: Patients are randomized to 1 of 2 treatment regimens. Regimen I (low-dose of RO4929097): Patients receive low-dose RO4929097 orally (PO) once daily on days 1-3, 8-10, and 15-17 and midazolam hydrochloride IV over 1 minute, omeprazole PO, tolbutamide PO, and dextromethorphan hydrobromide PO on days 1 and 10. After completion of course 1, patients are randomized to 1 of 2 treatment arms. Arm A: Patients receive low-dose RO4929097 PO once daily on days 1-3, 8-10, and 15-17 and ketoconazole PO once daily on days 1-10 for course 2 only. For course 3 and beyond, patients receive low-dose RO4929097 on days 1-3, 8-10, and 15-17. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Arm B: Patients receive low-dose RO4929097 PO once daily on days 1-3, 8-10, and 15-17 and rifampin PO once daily on days 1-10 for course 2 only. For course 3 and beyond, patients receive low-dose RO4929097 on days 1-3, 8-10, and 15-17. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Regimen II (high-dose of RO4929097): Patients receive high-dose RO4929097 PO once daily on days 1-3, 8-10, and 15-17 and midazolam hydrochloride IV, oral omeprazole, oral tolbutamide, and oral dextromethorphan hydrobromide on days 1 and 10. After completion of course 1, patients are randomized to 1 of 2 treatment arms. Arm A: Patients receive high-dose RO4929097 once daily on days 1-3, 8-10, and 15-17 and oral ketoconazole once daily on days 1-10 for course 2 only. Arm B: Patients receive high-dose RO4929097 once daily on days 1-3, 8-10, and 15-17 and oral rifampin once daily on days 1-10 for course 2 only. In all arms, treatment with RO4929097 repeats every 21 days for \>= 3 courses in the absence of disease progression or unacceptable toxicity. Patients undergo blood sample collection at baseline and periodically during study for pharmacokinetics studies and evaluation of SNPs in CYP2D6, CYP2C9, ABCB1, and CYP3A4/5. After completion of study therapy, patients are followed up for 30 days.

Conditions

• Adult Solid Neoplasm

Interventions

Type	Name	Description
DRUG	Gamma-Secretase Inhibitor RO4929097	Given PO
DRUG	Ketoconazole	Given PO
DRUG	Rifampin	Given PO
DRUG	Midazolam Hydrochloride	Given IV
DRUG	Omeprazole	Given PO
DRUG	Tolbutamide	Given PO
DRUG	Dextromethorphan Hydrobromide	Given PO
OTHER	Pharmacological Study	Correlative studies
OTHER	Laboratory Biomarker Analysis	Correlative studies

Timeline

• Start date: 2010-09-01
• Primary completion: 2012-07-01
• Completion: 2014-12-01
• First posted: 2010-10-11
• Last updated: 2014-12-23

Locations

1 site across 1 country: United States