Bevacizumab Plus Fluorouracil and Leucovorin in Treating Patients With Locally Advanced or Metastatic Stage IV Colorectal Cancer That Has Progressed After Standard Chemotherapy

Colorectal Cancer Clinical Trial

Official title:

A Multicenter Study of the Anti-VEGF Monoclonal Antibody Bevacizumab (Avastin®) Plus 5-Fluorouracil/Leucovorin in Patients With Metastatic Colorectal Cancers That Have Progressed After Standard Chemotherapy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00066846
• Other study ID #: CDR0000320506
• Secondary ID: CTEP-TRC-0301
• Status: Completed
• Phase: Phase 2
• First received: August 6, 2003
• Last updated: June 18, 2013
• Start date: August 2003
• Est. completion date: July 2007

Study information

• Verified date: April 2004
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Bevacizumab may stop the growth of tumor cells by blocking the enzymes necessary for cancer cell growth. Drugs used in chemotherapy such as fluorouracil and leucovorin use different ways to stop tumor cells from dividing so they stop growing or die. Combining bevacizumab with fluorouracil and leucovorin may kill more tumor cells.

PURPOSE: Phase II trial to study the effectiveness of combining bevacizumab with fluorouracil and leucovorin in treating patients who have locally advanced or metastatic stage IV colorectal cancer that has progressed after standard chemotherapy.

Description:

OBJECTIVES:

• Determine the response rate of patients treated with bevacizumab, fluorouracil, and leucovorin calcium for stage IV colorectal cancer that has progressed after standard chemotherapy.

• Determine the time to progression and overall survival of patients treated with this regimen.

• Determine the safety of administering "bolus" and continuous infusion fluorouracil and leucovorin calcium in patients treated with this regimen.

OUTLINE: This is an open-label, multicenter study. Patients receive 1 of 2 treatment regimens.

• Regimen I: Patients receive bevacizumab IV on days 1, 15, 29, and 42 (every 2 weeks) and leucovorin calcium (CF) IV over 2 hours and fluorouracil (5-FU) IV bolus on days 1, 8, 15, 22, 29, and 36.

• Regimen II: Patients receive bevacizumab as in regimen I and CF IV over 2 hours and 5-FU IV bolus followed by a continuous infusion over 22 hours on days 1, 2, 15, 16, 29, 30, 43, and 44.

For both regimens, courses repeat every 8 weeks in the absence of disease progression or unacceptable toxicity.

Patients are followed for tumor response and survival.

PROJECTED ACCRUAL: Various NCI-designated Clinical Cancer Centers and other medical institutions across the United States will participate in this study. A total of 35-125 patients will be accrued for this study within 3 months.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 0
• Est. completion date: July 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed colorectal adenocarcinoma

• Stage IV (metastatic) disease

• Not curable by surgery or radiotherapy

• Must have received prior standard chemotherapy regimens, including oxaliplatin and irinotecan, and meet both of the following criteria:

• Disease progression during or after irinotecan-based chemotherapy for metastatic disease OR relapsed disease within 6 months after adjuvant irinotecan-based therapy

• Disease progression during or after oxaliplatin-based chemotherapy for metastatic disease OR relapsed disease within 6 months after adjuvant oxaliplatin-based therapy

• No brain metastases

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• ECOG 0-2 OR

• Karnofsky 60-100%

Life expectancy

• Not specified

Hematopoietic

• Absolute granulocyte count at least 1,500/mm^3

• Platelet count at least 100,000/mm^3

• Hemoglobin at least 9 g/dL (transfusion allowed)

• No evidence of bleeding diathesis or coagulopathy

Hepatic

• Bilirubin no greater than 1.5 mg/dL

• AST less than 5 times upper limit of normal (ULN)

• Alkaline phosphatase less than 5 times ULN

• PT and INR no greater than 1.5 times ULN

• PTT no greater than ULN

Renal

• Creatinine no greater than 1.5 times ULN

• Proteinuria less than grade 1 OR

• Proteinuria less than 500 mg/24 hours

Cardiovascular

• No prior stroke

• No uncontrolled high blood pressure

• No symptomatic congestive heart failure

• No unstable angina pectoris

• No cardiac arrhythmia

• No myocardial infarction within the past 6 months

• No New York Heart Association class III or IV heart disease

• No thromboembolism within the past 6 months

Other

• Chemonaive

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception during and for at least 3 months after study participation

• No significant traumatic injury within the past 6 weeks

• No prior allergic reaction attributed to compounds of similar chemical or biological composition to bevacizumab or other study agents

• No active infection

• No psychiatric illness or social situation that would preclude study compliance

• No serious nonhealing wound (including wounds healing by secondary intention), ulcer, or bone fracture

• No CNS disease, including either of the following:

• Primary brain tumor

• Seizures not controlled with standard medical therapy

PRIOR CONCURRENT THERAPY:

Biologic therapy

• At least 8 weeks since prior monoclonal antibody therapy

• No prior bevacizumab

Chemotherapy

• See Disease Characteristics

Endocrine therapy

• Not specified

Radiotherapy

• At least 4 weeks since prior major radiotherapy (e.g., chest or bone palliative radiotherapy)

Surgery

• More than 6 weeks since prior major surgical procedure or open biopsy

• More than 7 days since prior fine needle aspiration or core biopsy

• No concurrent surgery

Other

• Recovered from prior therapy

• At least 3 weeks since prior cytotoxic agents

• No concurrent therapeutic anticoagulation

• Prophylactic anticoagulation of venous access devices allowed provided PT/INR or PTT criteria are met

• No concurrent chronic aspirin (greater than 325 mg/day) or nonsteroidal anti-inflammatory drugs

• No concurrent combination antiretroviral therapy for HIV-positive patients

• No other concurrent investigational or commercial agents for the malignancy

Study Design

Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Colorectal Cancer
• Colorectal Neoplasms

Intervention

Biological:
• bevacizumab

Drug:
• fluorouracil

• leucovorin calcium

Locations

Country	Name	City	State
United States	Providence Alaska Medical Center	Anchorage	Alaska
United States	Saint Joseph Mercy Health System	Ann Arbor	Michigan
United States	CCOP - Atlanta Regional	Atlanta	Georgia
United States	University of Colorado Cancer Center at University of Colorado Health Sciences Center	Aurora	Colorado
United States	Cancer Care of Maine	Bangor	Maine
United States	CCOP - Montana Cancer Consortium	Billings	Montana
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	Fletcher Allen Health Care - University Health Center Campus	Burlington	Vermont
United States	Robert H. Lurie Comprehensive Cancer Center, Northwestern University	Chicago	Illinois
United States	Ireland Cancer Center	Cleveland	Ohio
United States	St. Mary's/Duluth Clinic Cancer Center	Duluth	Minnesota
United States	Duke Comprehensive Cancer Center	Durham	North Carolina
United States	Meritcare Roger Maris Cancer Center	Fargo	North Dakota
United States	Holden Comprehensive Cancer Center	Iowa City	Iowa
United States	University of Mississippi Medical Center	Jackson	Mississippi
United States	Southern Nevada Cancer Research Foundation	Las Vegas	Nevada
United States	Norris Cotton Cancer Center	Lebanon	New Hampshire
United States	Jonsson Comprehensive Cancer Center, UCLA	Los Angeles	California
United States	USC/Norris Comprehensive Cancer Center and Hospital	Los Angeles	California
United States	Loyola University Medical Center	Maywood	Illinois
United States	Yale Comprehensive Cancer Center	New Haven	Connecticut
United States	New York Weill Cornell Cancer Center at Cornell University	New York	New York
United States	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma
United States	Abramson Cancer Center of the University of Pennsylvania	Philadelphia	Pennsylvania
United States	Kimmel Cancer Center of Thomas Jefferson University - Philadelphia	Philadelphia	Pennsylvania
United States	Massey Cancer Center	Richmond	Virginia
United States	CCOP - Virginia Mason Research Center	Seattle	Washington
United States	Seattle Cancer Care Alliance	Seattle	Washington
United States	Siouxland Hematology-Oncology	Sioux City	Iowa
United States	Sioux Valley Clinics - Oncology	Sioux Falls	South Dakota
United States	Lombardi Cancer Center	Washington	District of Columbia
United States	CCOP - Wichita	Wichita	Kansas
United States	Comprehensive Cancer Center at Wake Forest University	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

References & Publications (1)

Chen HX, Mooney M, Boron M, Vena D, Mosby K, Grochow L, Jaffe C, Rubinstein L, Zwiebel J, Kaplan RS. Phase II multicenter trial of bevacizumab plus fluorouracil and leucovorin in patients with advanced refractory colorectal cancer: an NCI Treatment Referr — View Citation