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

Sponsor:	Genentech
Information provided by:	Genentech
ClinicalTrials.gov Identifier:	NCT00636610

Purpose

This is a randomized, placebo-controlled, double-blind study of GDC-0449 added to biochemotherapy standard-of-care regimens for metastatic CRC, with treatment until disease progression. Patients will receive either FOLFOX or FOLFIRI chemotherapy with bevacizumab. The decision of which regimen (FOLFOX or FOLFIRI) to use will be made by the treating physician and patient. Patients will be randomized to receive GDC-0449 or placebo and will be stratified based on the chemotherapy regimen chosen and whether or not Response Evaluation Criteria in Solid Tumors (RECIST) measurable disease is present at baseline.

Condition	Intervention	Phase
Metastatic Colorectal Cancer	Drug: bevacizumab Drug: chemotherapy Drug: GDC-0449 Drug: placebo	Phase II

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Investigator), Placebo Control, Parallel Assignment
Official Title:	A Randomized, Placebo-Controlled Phase II Study of GDC-0449 (Systemic Hedgehog Antagonist) With Concurrent Chemotherapy and Bevacizumab As First-Line Therapy for Metastatic Colorectal Cancer

Resource links provided by NLM:

MedlinePlus related topics: Cancer Colorectal Cancer

Drug Information available for: Bevacizumab

U.S. FDA Resources

Further study details as provided by Genentech:

Primary Outcome Measures:

Progression-free survival [ Time Frame: From randomization to disease progression or death ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Measurement of Hedgehog ligand expression in archival tissue [ Time Frame: Length of study ] [ Designated as safety issue: No ]
Number and attribution of Grade 3 and 4 adverse events [ Time Frame: Length of study ] [ Designated as safety issue: No ]
Incidence, nature, and severity of all adverse events [ Time Frame: Length of study ] [ Designated as safety issue: No ]

Enrollment:	198
Study Start Date:	March 2008
Estimated Primary Completion Date:	March 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Experimental	Drug: bevacizumab Intravenous repeating dose Drug: chemotherapy Intravenous repeating dose Drug: GDC-0449 Oral repeating dose
2: Placebo Comparator	Drug: bevacizumab Intravenous repeating dose Drug: chemotherapy Intravenous repeating dose Drug: placebo Oral repeating dose

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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
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 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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00636610

Sponsors and Collaborators

Genentech

Investigators

Study Director:

Jennifer Low, M.D., Ph.D.

Genentech

More Information

No publications provided

Responsible Party:	Genentech, Inc. ( Clinical Trials Posting Group )
Study ID Numbers:	SHH4429g
Study First Received:	March 5, 2008
Last Updated:	September 8, 2009
ClinicalTrials.gov Identifier:	NCT00636610 History of Changes
Health Authority:	United States: Food and Drug Administration

Keywords provided by Genentech:

Hedgehog
CRC
Colorectal Cancer
Hedgehog Pathway Inhibitor

Additional relevant MeSH terms:

Digestive System Neoplasms
Antineoplastic Agents
Gastrointestinal Diseases
Growth Substances
Physiological Effects of Drugs
Colonic Diseases
Bevacizumab
Intestinal Diseases
Rectal Diseases
Angiogenesis Inhibitors

Pharmacologic Actions
Intestinal Neoplasms
Neoplasms
Neoplasms by Site
Digestive System Diseases
Therapeutic Uses
Gastrointestinal Neoplasms
Growth Inhibitors
Angiogenesis Modulating Agents
Colorectal Neoplasms

ClinicalTrials.gov processed this record on November 05, 2009