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

This study has been completed.
Sponsor:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00066846
First received: August 6, 2003
Last updated: June 18, 2013
Last verified: April 2004
  Purpose

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.


Condition Intervention Phase
Colorectal Cancer
Biological: bevacizumab
Drug: fluorouracil
Drug: leucovorin calcium
Phase 2

Study Type: Interventional
Study Design: Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


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

Study Start Date: August 2003
Study Completion Date: July 2007
Detailed 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00066846

  Show 33 Study Locations
Sponsors and Collaborators
Investigators
Principal Investigator: Helen X. Chen, MD NCI - Investigational Drug Branch
  More Information

Additional Information:
Publications:
ClinicalTrials.gov Identifier: NCT00066846     History of Changes
Other Study ID Numbers: CDR0000320506, CTEP-TRC-0301
Study First Received: August 6, 2003
Last Updated: June 18, 2013
Health Authority: United States: Federal Government

Keywords provided by National Cancer Institute (NCI):
adenocarcinoma of the colon
adenocarcinoma of the rectum
stage IV rectal cancer
recurrent rectal cancer
stage IV colon cancer
recurrent colon cancer

Additional relevant MeSH terms:
Colorectal Neoplasms
Colonic Diseases
Digestive System Diseases
Digestive System Neoplasms
Gastrointestinal Diseases
Gastrointestinal Neoplasms
Intestinal Diseases
Intestinal Neoplasms
Neoplasms
Neoplasms by Site
Rectal Diseases
Bevacizumab
Fluorouracil
Levoleucovorin
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Antidotes
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Growth Inhibitors
Growth Substances
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Protective Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014