Clinical trial NCT00636610: A Study of Vismodegib (GDC-0449, Hedgehog Pathway Inhibitor) With Concurrent Chemotherapy and Bevacizumab As First-Line Therapy for Metastatic Colorectal Cancer
Official title: A Randomized, Placebo-Controlled Phase II Study of Vismodegib (GDC-0449, Systemic Hedgehog Antagonist) With Concurrent Chemotherapy and Bevacizumab As First-Line Therapy for Metastatic Colorectal Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Metastatic Colorectal Cancer
Keywords: Hedgehog
CRC
Colorectal Cancer
Hedgehog Pathway Inhibitor
Lead sponsor: Genentech, Inc.
Sponsor class: INDUSTRY
First posted: 2008-03-14
Enrollment: 199
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Progression-free Survival (PFS)
timeFrame: From first treatment through the data cut-off date of March 15, 2010, up to 90 weeks
Secondary outcomes:
measure: Progression-free Survival (PFS) in Patients With Various Degrees of Hedgehog Antigen Tumor Expression
timeFrame: From first treatment through the data cut-off date of March 15, 2010, up to 90 weeks
Other outcomes:
Locations:
Study officials:
affiliation: Genentech, Inc.
name: Jennifer Low, M.D., Ph.D.
role: STUDY_DIRECTOR
References: