A Study of Vismodegib (GDC-0449, Hedgehog Pathway Inhibitor) With Concurrent Chemotherapy and Bevacizumab As First-Line Therapy for Metastatic Colorectal Cancer

Genentech

Status and phase: Completed; Phase 2

Conditions: Metastatic Colorectal Cancer

Treatments: Drug: FOLFIRI; Drug: Bevacizumab; Drug: Placebo to vismodegib; Drug: Vismodegib 150 mg; Drug: Modified FOLFOX

Study type: Interventional

Funder types: Industry

Identifiers

NCT00636610

SHH4429g

Details and patient eligibility

About

This was a randomized, placebo-controlled, double-blind study of vismodegib (GDC-0449) added to biochemotherapy standard-of-care regimens for metastatic colorectal cancer (CRC), with treatment until disease progression. Patients received either FOLFOX (FOL=leucovorin calcium [folinic acid], F=fluorouracil, OX=oxaliplatin) or FOLFIRI (FOL=leucovorin calcium [folinic acid] F=fluorouracil, IRI=irinotecan hydrochloride) chemotherapy with bevacizumab. The decision of which regimen (FOLFOX or FOLFIRI) to use was made by the treating physician and patient. Patients were randomized to receive vismodegib or placebo and were stratified based on the chemotherapy regimen chosen and whether or not Response Evaluation Criteria in Solid Tumors (RECIST) measurable disease was present at baseline.

Enrollment: 199 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Age ≥ 18 years
• Histologically confirmed metastatic colorectal cancer (CRC)
• Representative tumor specimens in paraffin blocks (preferred) or at least 15 unstained slides, with an associated pathology report, must be confirmed to be available and requested at any time prior to entry of study
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
• Adequate hematopoetic capacity
• Adequate hepatic function
• Adequate renal function
• Use of an effective method of barrier contraception (for women of childbearing potential)
• Signed informed consent

Exclusion criteria

• Prior chemotherapy for metastatic CRC or adjuvant chemotherapy for CRC within the prior 6 months
• Clinically suspected or confirmed CNS metastases or carcinomatous meningitis
• Major surgical procedure within 4 weeks prior to the first day of treatment in this study (Day 1)
• Pelvic radiation within 2 weeks prior to Day 1
• Wound dehiscence requiring intervention, gastrointestinal perforation, or bowel obstruction
• Pregnancy or lactation
• Uncontrolled medical illnesses including the following: Infection requiring intravenous (IV) antibiotics, congestive heart failure not controlled with medication, hypertension not controlled with medication
• Thromboembolic disease
• History of other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates use of an investigational drug or that might affect interpretation of the results of the study or render the patient at high risk from treatment complications

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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199 participants in 2 patient groups, including a placebo group

Vismodegib 150 mg

Experimental group

Description:

Patients received vismodegib 150 mg orally once daily starting on Day 3 of each 2-week treatment cycle. In addition, patients received either Modified FOLFOX (FOL=leucovorin calcium \[folinic acid\], F=fluorouracil, OX=oxaliplatin) + bevacizumab or FOLFIRI (FOL=leucovorin calcium \[folinic acid\] F=fluorouracil, IRI=irinotecan hydrochloride) + bevacizumab on Days 1-3 of each 2-week treatment cycle. The decision of which regimen (FOLFOX or FOLFIRI) to use was made by the treating physician and patient.

Treatment:

Drug: FOLFIRI

Drug: Bevacizumab

Drug: Vismodegib 150 mg

Drug: Modified FOLFOX

Placebo to vismodegib

Placebo Comparator group

Description:

Patients received placebo to vismodegib orally once daily starting on Day 3 of each 2-week treatment. In addition, patients received either Modified FOLFOX (FOL=leucovorin calcium \[folinic acid\], F=fluorouracil, OX=oxaliplatin) + bevacizumab or FOLFIRI (FOL=leucovorin calcium \[folinic acid\] F=fluorouracil, IRI=irinotecan hydrochloride) + bevacizumab on Days 1-3 of each 2-week treatment cycle. The decision of which regimen (FOLFOX or FOLFIRI) to use was made by the treating physician and patient.

Treatment:

Drug: FOLFIRI

Drug: Bevacizumab

Drug: Placebo to vismodegib

Drug: Modified FOLFOX