Combination Chemotherapy With or Without Bevacizumab Compared With Bevacizumab Alone in Treating Patients With Advanced or Metastatic Colorectal Cancer That Has Been Previously Treated - Full Text View

Sponsors and Collaborators:	Eastern Cooperative Oncology Group National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00025337

Purpose

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Monoclonal antibodies such as bevacizumab can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Combining monoclonal antibody therapy with combination chemotherapy may kill more tumor cells. It is not yet known if bevacizumab is more effective with or without combination chemotherapy in treating colorectal cancer.

PURPOSE: Randomized phase III trial to compare the effectiveness of combination chemotherapy with or without bevacizumab in treating patients who have advanced or metastatic colorectal cancer that has been previously treated.

Condition	Intervention	Phase
Colorectal Cancer	Drug: FOLFOX-4 regimen Drug: bevacizumab Drug: fluorouracil Drug: leucovorin calcium Drug: oxaliplatin	Phase III

MedlinePlus related topics: Cancer Colorectal Cancer

Drug Information available for: Leucovorin Calcium Citrovorum factor Folinic acid calcium salt pentahydrate Leucovorin Bevacizumab Fluorouracil Oxaliplatin Calcium gluconate

U.S. FDA Resources

Study Type:

Interventional

Study Design:

Treatment, Randomized, Active Control

Official Title:

Phase III Trial of Bevacizumab (NSC 704865), Oxaliplatin (NSC 266046), Fluorouracil and Leucovorin Versus Oxaliplatin, Fluorouracil and Leucovorin Versus Bevacizumab Alone in Previously Treated Patients With Advanced Colorectal Cancer

Further study details as provided by National Cancer Institute (NCI):

Study Start Date:

October 2001

Primary Completion Date:

April 2007 (Final data collection date for primary outcome measure)

Detailed Description:

OBJECTIVES:

Compare the response, time to progression, and overall survival of patients with previously treated advanced or metastatic colorectal adenocarcinoma treated with oxaliplatin, leucovorin calcium, and fluorouracil with or without bevacizumab versus bevacizumab only. (Arm III closed to accrual as of 03/11/2003).
Compare the toxicity of these regimens in these patients.

OUTLINE: This is a randomized study. Patients are stratified according to ECOG performance status (0 vs 1 or 2), and prior radiotherapy (yes vs no). Patients are randomized to 1 of 3 treatment arms.

Arm I: Patients receive bevacizumab IV over 30-90 minutes and oxaliplatin IV over 2 hours on day 1. Patients also receive leucovorin calcium IV over 2 hours and fluorouracil (5-FU) IV over 22 hours on days 1 and 2.
Arm II: Patients receive oxaliplatin, leucovorin calcium, and 5-FU as in arm I.
Arm III: Patients receive bevacizumab as in arm I. (Arm closed to accrual as of 03/11/2003).

Courses in all arms repeat every 2 weeks in the absence of disease progression or unacceptable toxicity. Patients who achieve a complete response may receive 2 additional courses.

Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 880 patients (293 per treatment arm) will be accrued for this study within 18 months. (Arm III closed to accual as of 03/11/2003).

Eligibility

Ages Eligible for Study:

18 Years and older

Genders Eligible for Study:

Both

Accepts Healthy Volunteers:

No

Criteria

DISEASE CHARACTERISTICS:

Histologically confirmed adenocarcinoma of the colon or rectum
- Advanced or metastatic disease
- Must have received a fluoropyrimidine-based regimen and an irinotecan-based regimen, either alone or in combination, for advanced disease
- May have relapsed within 6 months of adjuvant therapy with fluorouracil (5-FU) (or combination 5-FU and irinotecan) and progressed after single-agent irinotecan
Measurable disease
No known brain metastases

PATIENT CHARACTERISTICS:

Age:

18 and over

Performance status:

ECOG 0-2

Life expectancy:

Not specified

Hematopoietic:

Absolute neutrophil count at least 1,500/mm^3
Platelet count at least 100,000/mm^3
No history of thrombotic or hemorrhagic disorders

Hepatic:

Bilirubin no greater than 1.5 times upper limit of normal (ULN)
AST no greater than 5 times ULN
INR no greater than 1.5
PTT no greater than ULN

Renal:

Creatinine no greater than 1.5 times ULN
Proteinuria less than 1+ (i.e., 0 or trace) OR
Protein less than 500 mg by 24-hour urine collection
Proteinuria secondary to ureteral stents allowed
- No proteinuria secondary to nephropathy

Cardiovascular:

Controlled hypertension (less than 150/100 mm Hg) allowed if on a stable antihypertensive regimen
No prior myocardial infarction
No uncontrolled congestive heart failure
No unstable angina within the past 3 months

Other:

No serious nonhealing wound, ulcer, or bone fracture
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

No prior bevacizumab

Chemotherapy:

See Disease Characteristics
Recovered from prior chemotherapy
No prior oxaliplatin

Endocrine therapy:

Not specified

Radiotherapy:

At least 2 weeks since prior radiotherapy and recovered

Surgery:

At least 28 days since prior major surgical procedure

Other:

At least 10 days since prior aspirin dose of more than 325 mg/day
No concurrent therapeutic anticoagulation except prophylactic anticoagulation of venous access device
No concurrent antiplatelet agents (e.g., dipyridamole, ticlopidine, clopidogrel, or cilostazol)
No concurrent oral cryotherapy on day 1 of oxaliplatin administration

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00025337

Show 37 Study Locations

Sponsors and Collaborators

Eastern Cooperative Oncology Group

National Cancer Institute (NCI)

Investigators

Study Chair:

Bruce J. Giantonio, MD

Kimmel Cancer Center (KCC)

More Information

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Publications of Results:

Catalano PJ, Mitchell EP, Giantonio BJ, et al.: Outcomes differences for African Americans and Caucasians treated with bevacizumab, FOLFOX4 or the combination in patients with metastatic colorectal cancer (MCRC): results from the Eastern Cooperative Oncology Group Study E3200. [Abstract] J Clin Oncol 25 (Suppl 18): A-4100, 2007.

Giantonio BJ, Catalano PJ, Meropol NJ, O'Dwyer PJ, Mitchell EP, Alberts SR, Schwartz MA, Benson AB 3rd; Eastern Cooperative Oncology Group Study E3200. Bevacizumab in combination with oxaliplatin, fluorouracil, and leucovorin (FOLFOX4) for previously treated metastatic colorectal cancer: results from the Eastern Cooperative Oncology Group Study E3200. J Clin Oncol. 2007 Apr 20;25(12):1539-44.

Giantonio BJ, Catalano PJ, O'Dwyer PJ, et al.: Impact of bevacizumab dose reduction on clinical outcomes for patients treated on the Eastern Cooperative Oncology Group's study E3200. [Abstract] J Clin Oncol 24 (Suppl 18): A-3538, 2006.

Giantonio BJ, Catalano PJ, Meropol NJ, et al.: High-dose bevacizumab improves survival when combined with FOLFOX4 in previously treated advanced colorectal cancer: results from the Eastern Cooperative Oncology Group (ECOG) study E3200. [Abstract] J Clin Oncol 23 (Suppl 16): A-2, 1s, 2005.

Mitchell EP, Alberts SR, Schwartz MA, et al.: High-dose bevacizumab in combination with FOLFOX4 improves survival in patients with previously treated advanced colorectal cancer: results from the Eastern Cooperative Oncology Group (ECOG) study E3200. [Abstract] American Society of Clinical Oncology 2005 Gastrointestinal Cancers Symposium, 27-29 January 2005, Miami, Florida. A-169a, 2005.

Giantonio BJ, Chen HX, Catalano PJ, et al.: Bowel perforation and fistula formation in colorectal cancer patients treated on Eastern Cooperative Oncology Group (ECOG) studies E2200 and E3200. [Abstract] J Clin Oncol 22 (Suppl 14): A-3017, 199s, 2004.

Benson AB, Catalano PJ, Meropol NJ, et al.: Bevacizumab (anti-VEGF) plus FOLFOX4 in previously treated advanced colorectal cancer (advCRC): an interim toxicity analysis of the Eastern Cooperative Oncology Group (ECOG) study E3200. [Abstract] Proceedings of the American Society of Clinical Oncology 22: A-975, 2003.

Other Publications:

Giantonio BJ, Meropol NJ, Catalano PJ, et al.: Magnitude of progression-free survival (PFS) improvement and treatment (Tx) duration in metastatic colorectal cancer (mCRC) for bevacizumab (BV) in combination with oxaliplatin-containing regimens: an analysis of two phase III studies. [Abstract] J Clin Oncol 25 (Suppl 18): A-4073, 2007.

Saif MW, Mehra R. Incidence and management of bevacizumab-related toxicities in colorectal cancer. Expert Opin Drug Saf. 2006 Jul;5(4):553-66. Review.

Gray R, Giantonio BJ, O'Dwyer PJ, et al.: The safety of adding angiogenesis inhibition into treatment for colorectal, breast, and lung cancer: the Eastern Cooperative Oncology Group's (ECOG) experience with bevacizumab (anti-VEGF). [Abstract] Proceedings of the American Society of Clinical Oncology 22: A-825, 2003.

Study ID Numbers:

CDR0000068951, E-3200

First Received:

October 11, 2001

Last Updated:

January 3, 2009

ClinicalTrials.gov Identifier:

NCT00025337

Health Authority:

United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

stage III colon cancer
stage IV colon cancer
stage III rectal cancer
stage IV rectal cancer

recurrent colon cancer
recurrent rectal cancer
adenocarcinoma of the colon
adenocarcinoma of the rectum

Study placed in the following topic categories:

Digestive System Neoplasms
Rectal Neoplasms
Gastrointestinal Diseases
Colonic Diseases
Leucovorin
Bevacizumab
Intestinal Diseases
Rectal Diseases
Recurrence
Intestinal Neoplasms

Rectal neoplasm
Calcium, Dietary
Oxaliplatin
Digestive System Diseases
Fluorouracil
Gastrointestinal Neoplasms
Adenocarcinoma
Rectal cancer
Colorectal Neoplasms

Additional relevant MeSH terms:

Antimetabolites
Antimetabolites, Antineoplastic
Vitamin B Complex
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Antineoplastic Agents
Growth Substances
Physiological Effects of Drugs
Angiogenesis Inhibitors

Immunosuppressive Agents
Pharmacologic Actions
Neoplasms
Neoplasms by Site
Therapeutic Uses
Vitamins
Growth Inhibitors
Angiogenesis Modulating Agents
Micronutrients

ClinicalTrials.gov processed this record on January 06, 2009