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

NCT01270438 | Withdrawn Phase 2

• 7 other identifiers: NCI-2011-02571CDR0000692198MSKCC-1019110-1918467U01CA069856N01CM62206
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 3

Brief 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.

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

Outcome Measures

Primary Outcomes (1)

• Progression-free survival of patients treated with FOLFOX6 plus bevacizumab with or without gamma-secretase inhibitor RO4929097

  Progression is defined as changes in RECIST 1.1-defined imaging, progression in non-target lesions as defined by RECIST 1.1, unequivocal clinical deterioration, or death from any cause.

  From start of treatment to time of progression, assessed up to 12 months

Secondary Outcomes (3)

• Objective response rate (complete or partial response) as measured by RECIST

  Assessed up to 12 months

• Incidence of dose-limiting and non-dose-limiting toxicities

  Assessed up to 12 months

• Pharmacokinetics and pharmacodynamics of gamma-secretase inhibitor RO4929097

  Baseline, and day 1 of courses 1 and 2

Study Arms (2)

Arm I (RO4929097, combination chemotherapy, bevacizumab)

EXPERIMENTAL

Patients receive FOLFOX6 regimen comprising oxaliplatin 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.

Drug: FOLFOX regimen; Drug: gamma-secretase/Notch signalling pathway inhibitor RO4929097; Biological: bevacizumab; Drug: oxaliplatin; Drug: leucovorin calcium; Drug: fluorouracil

Arm II (combination chemotherapy, bevacizumab)

EXPERIMENTAL

Patients receive FOLFOX6 regimen and bevacizumab as in arm I. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.

Drug: FOLFOX regimen; Biological: bevacizumab; Drug: oxaliplatin; Drug: leucovorin calcium; Drug: fluorouracil

Interventions

FOLFOX regimen DRUG

Given IV

Arm I (RO4929097, combination chemotherapy, bevacizumab); Arm II (combination chemotherapy, bevacizumab)

gamma-secretase/Notch signalling pathway inhibitor RO4929097 DRUG

Given orally

Arm I (RO4929097, combination chemotherapy, bevacizumab)

bevacizumab BIOLOGICAL

Given IV

Arm I (RO4929097, combination chemotherapy, bevacizumab); Arm II (combination chemotherapy, bevacizumab)

oxaliplatin DRUG

Given IV

Arm I (RO4929097, combination chemotherapy, bevacizumab); Arm II (combination chemotherapy, bevacizumab)

leucovorin calcium DRUG

Given IV

Arm I (RO4929097, combination chemotherapy, bevacizumab); Arm II (combination chemotherapy, bevacizumab)

fluorouracil DRUG

Given IV

Arm I (RO4929097, combination chemotherapy, bevacizumab); Arm II (combination chemotherapy, bevacizumab)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically or cytologically confirmed adenocarcinoma of the colon or adenocarcinoma of the rectum
• Metastatic disease by imaging
• Measurable disease, defined as ≥ 1 lesion that can be accurately measured in ≥ 1 dimension (longest diameter to be recorded) as ≥ 20mm by conventional techniques or as ≥ 10 mm by spiral CT scan
• No known brain metastases
• ECOG performance status 0-1
• ANC ≥ 1,500/mm³
• WBC ≥ 3,000/mm³
• Platelet count ≥ 100,000/mm³ (without a platelet transfusion ≤ 14 days prior to study)
• Hemoglobin ≥ 9 g/dL
• Serum creatinine ≤ 1.5 times upper limit of normal (ULN)
• Urine protein:creatinine ≤ 0.5 or proteinuria \< 1,000 mg on 24-hour urine collection
• Total bilirubin ≤ 1.5 times ULN
• AST and ALT ≤ 2.5 times ULN (≤ 5.0 times ULN for patients with liver metastases)
• Albumin ≥ 2.5 g/dL
• Amylase ≤ 2 times ULN

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (3)

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center

Columbus, Ohio, 43210, United States

Location

MeSH Terms

Conditions

Colonic Neoplasms; Rectal Neoplasms

Interventions

Folfox protocol; 2,2-dimethyl-N-(6-oxo-6,7-dihydro-5H-dibenzo(b,d)azepin-7-yl)-N'-(2,2,3,3,3-pentafluoropropyl)malonamide; Bevacizumab; Oxaliplatin; Leucovorin; Fluorouracil

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Coordination Complexes; Organic Chemicals; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Coenzymes; Enzymes and Coenzymes; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring

Study Officials

• Neil Segal

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 4, 2011
• First Posted: January 5, 2011
• Study Start: December 1, 2010
• Primary Completion: August 1, 2011
• Study Completion: August 1, 2013
• Last Updated: April 4, 2017

Record last verified: 2017-04

Locations

US (3)