NCT01270438

Combination Chemotherapy and Bevacizumab With or Without RO4929097 in Treating Patients With Metastatic Colorectal Cancer

A Phase 2 Study of RO4929097 (NSC 749225) in Combination With FOLFOX Plus Bevacizumab Versus FOLFOX Plus Bevacizumab Alone for the First-Line Treatment of Patients With Metastatic Colorectal Cancer (NCI #8467)

• Status: Withdrawn
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 0 (actual)
• Sponsor: National Cancer Institute (NCI) · NIH
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase II clinical trial is studying how well giving combination chemotherapy and bevacizumab with or without RO4929097 works in treating patients with metastatic colorectal cancer. Drugs used in chemotherapy, such as oxaliplatin, leucovorin calcium, and fluorouracil, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. RO4929097 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known whether combination chemotherapy and bevacizumab is more effective with RO4929097 in treating patients with colorectal cancer.

Detailed description

PRIMARY OBJECTIVES: I. To estimate the efficacy, as determined by progression-free survival, of FOLFOX6 and bevacizumab with versus without gamma-secretase inhibitor RO4929097 (RO4929097). SECONDARY OBJECTIVES: I. To estimate the clinical benefit of RO4929097 in combination with mFOLFOX6 and bevacizumab, as measured by objective response rate. II. To evaluate the safety and tolerability of RO4929097 in combination with mFOLFOX6 chemotherapy and bevacizumab. III. To evaluate the pharmacokinetics (PK) and pharmacodynamics (PD) of RO4929097 in combination with mFOLFOX6 and bevacizumab. IV. To investigate PD response of RO4929097 in combination with mFOLFOX6 chemotherapy and bevacizumab, as assessed by direct measurement of gamma-secretase enzyme activity, in tumor samples. V. (Exploratory) To investigate the Notch signaling pathway genes targeted by RO4929097 in combination with mFOLFOX6 chemotherapy and bevacizumab and correlate with clinical outcome. VI. (Exploratory) To investigate the Ras signaling pathway genes targeted by RO4929097 in combination with mFOLFOX6 chemotherapy and bevacizumab and correlate with clinical outcome. VII. (Exploratory) To investigate putative colorectal cancer stem cells targeted by RO4929097 in combination with mFOLFOX6 chemotherapy and bevacizumab and correlate with clinical outcome. OUTLINE: This is a multicenter study. Patients are stratified according to participating center, prior therapy (adjuvant/neoadjuvant vs none), and number of organs\* involved by metastases (1 vs \> 1). Patients are randomized to 1 of 2 treatment arms. NOTE: \*Lesions all in the liver would be considered as 1 organ involved. ARM I: Patients receive FOLFOX6 regimen comprising oxaliplatin intravenously (IV) over 2 hours, leucovorin calcium IV over 2 hours, fluorouracil IV continuously over 46 hours, and bevacizumab IV over 30-90 minutes on days 1-2. Patients also receive oral gamma-secretase inhibitor RO4929097 on days 1-3 and 8-10. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity (RO4929097 is given for up to 12 courses). ARM II: Patients receive FOLFOX6 regimen and bevacizumab as in arm I. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity. Patients may undergo blood sample collection at baseline and periodically during study for pharmacokinetic, pharmacodynamic, and correlative studies. After completion of study therapy, patients are followed up for 12 months.

Conditions

• Adenocarcinoma of the Colon
• Adenocarcinoma of the Rectum
• Recurrent Colon Cancer
• Recurrent Rectal Cancer
• Stage IVA Colon Cancer
• Stage IVA Rectal Cancer
• Stage IVB Colon Cancer
• Stage IVB Rectal Cancer

Interventions

Type	Name	Description
DRUG	FOLFOX regimen	Given IV
DRUG	gamma-secretase/Notch signalling pathway inhibitor RO4929097	Given orally
BIOLOGICAL	bevacizumab	Given IV
DRUG	oxaliplatin	Given IV
DRUG	leucovorin calcium	Given IV
DRUG	fluorouracil	Given IV

Timeline

• Start date: 2010-12-01
• Primary completion: 2011-08-01
• Completion: 2013-08-01
• First posted: 2011-01-05
• Last updated: 2017-04-04

Locations

3 sites across 1 country: United States