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

NCT ID: NCT00066846

Last Updated: 2013-06-20

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Study Classification

INTERVENTIONAL

Study Start Date

2003-08-31

Study Completion Date

2007-07-31

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Colorectal Cancer

Study Design

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Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Interventions

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bevacizumab

Intervention Type BIOLOGICAL

fluorouracil

Intervention Type DRUG

leucovorin calcium

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role lead

Principal Investigators

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Helen X. Chen, MD

Role: PRINCIPAL_INVESTIGATOR

NCI - Investigational Drug Branch

Locations

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Providence Alaska Medical Center

Anchorage, Alaska, United States

Site Status

Jonsson Comprehensive Cancer Center, UCLA

Los Angeles, California, United States

Site Status

USC/Norris Comprehensive Cancer Center and Hospital

Los Angeles, California, United States

Site Status

University of Colorado Cancer Center at University of Colorado Health Sciences Center

Aurora, Colorado, United States

Site Status

Yale Comprehensive Cancer Center

New Haven, Connecticut, United States

Site Status

Lombardi Cancer Center

Washington D.C., District of Columbia, United States

Site Status

CCOP - Atlanta Regional

Atlanta, Georgia, United States

Site Status

Robert H. Lurie Comprehensive Cancer Center, Northwestern University

Chicago, Illinois, United States

Site Status

Loyola University Medical Center

Maywood, Illinois, United States

Site Status

Holden Comprehensive Cancer Center

Iowa City, Iowa, United States

Site Status

Siouxland Hematology-Oncology

Sioux City, Iowa, United States

Site Status

CCOP - Wichita

Wichita, Kansas, United States

Site Status

Cancer Care of Maine

Bangor, Maine, United States

Site Status

Saint Joseph Mercy Health System

Ann Arbor, Michigan, United States

Site Status

St. Mary's/Duluth Clinic Cancer Center

Duluth, Minnesota, United States

Site Status

University of Mississippi Medical Center

Jackson, Mississippi, United States

Site Status

CCOP - Montana Cancer Consortium

Billings, Montana, United States

Site Status

Southern Nevada Cancer Research Foundation

Las Vegas, Nevada, United States

Site Status

Norris Cotton Cancer Center

Lebanon, New Hampshire, United States

Site Status

Roswell Park Cancer Institute

Buffalo, New York, United States

Site Status

New York Weill Cornell Cancer Center at Cornell University

New York, New York, United States

Site Status

Duke Comprehensive Cancer Center

Durham, North Carolina, United States

Site Status

Comprehensive Cancer Center at Wake Forest University

Winston-Salem, North Carolina, United States

Site Status

Meritcare Roger Maris Cancer Center

Fargo, North Dakota, United States

Site Status

Ireland Cancer Center

Cleveland, Ohio, United States

Site Status

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, United States

Site Status

Abramson Cancer Center of the University of Pennsylvania

Philadelphia, Pennsylvania, United States

Site Status

Kimmel Cancer Center of Thomas Jefferson University - Philadelphia

Philadelphia, Pennsylvania, United States

Site Status

Sioux Valley Clinics - Oncology

Sioux Falls, South Dakota, United States

Site Status

Fletcher Allen Health Care - University Health Center Campus

Burlington, Vermont, United States

Site Status

Massey Cancer Center

Richmond, Virginia, United States

Site Status

CCOP - Virginia Mason Research Center

Seattle, Washington, United States

Site Status

Seattle Cancer Care Alliance

Seattle, Washington, United States

Site Status

Countries

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United States

References

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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 Referral Center Trial TRC-0301. J Clin Oncol. 2006 Jul 20;24(21):3354-60. doi: 10.1200/JCO.2005.05.1573.

Reference Type RESULT
PMID: 16849749 (View on PubMed)

Other Identifiers

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CTEP-TRC-0301

Identifier Type: -

Identifier Source: secondary_id

CDR0000320506

Identifier Type: -

Identifier Source: org_study_id

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