A Study of Systemic Hedgehog Antagonist With Concurrent Chemotherapy and Bevacizumab As First-Line Therapy for Metastatic Colorectal Cancer - Full Text View

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: GDC-0449 Drug: placebo Drug: bevacizumab Drug: chemotherapy	Phase II

Genetics Home Reference related topics:

Colorectal Cancer

MedlinePlus related topics:

Cancer Colorectal Cancer

ChemIDplus related topics:

Bevacizumab

U.S. FDA Resources

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

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 ]

Estimated Enrollment:	150
Study Start Date:	March 2008
Estimated Study Completion Date:	March 2011

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

Contacts


Contact: Lisa Nelson		nelson.lisa@gene.com

Show 25 Study Locations

Sponsors and Collaborators

Genentech

Investigators


Study Director:	Jennifer Low, M.D., Ph.D.	Genentech

More Information

Responsible Party:	Genentech, Inc. ( Jennifer Low, M.D., Ph.D., Study Director )
Study ID Numbers:	SHH4429g
First Received:	March 5, 2008
Last Updated:	June 26, 2008
ClinicalTrials.gov Identifier:	NCT00636610
Health Authority:	United States: Food and Drug Administration

Keywords provided by Genentech:

Hedgehog

CRC

Colorectal Cancer

Study placed in the following topic categories:

Digestive System Neoplasms

Gastrointestinal Diseases

Colonic Diseases

Gastrointestinal Neoplasms

Bevacizumab

Intestinal Diseases

Rectal Diseases

Intestinal Neoplasms

Colorectal Neoplasms

Additional relevant MeSH terms:

Neoplasms

Digestive System Diseases

Neoplasms by Site

Antineoplastic Agents

Therapeutic Uses

Growth Substances

Physiological Effects of Drugs

Growth Inhibitors

Angiogenesis Modulating Agents

Angiogenesis Inhibitors

Pharmacologic Actions

ClinicalTrials.gov processed this record on July 03, 2008

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