Combination Chemotherapy Plus Trastuzumab in Treating Patients With Advanced, Recurrent, or Metastatic Colorectal Cancer

This study has been terminated.
(lack of sufficient accrual)
Sponsor:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00006015
First received: July 5, 2000
Last updated: May 1, 2013
Last verified: June 2011
  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 trastuzumab can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells.

PURPOSE: This phase II trial is studying combination chemotherapy plus trastuzumab to see how well it works in treating patients with advanced, recurrent, or metastatic colorectal cancer.


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

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Study Evaluating the Combination of 5-Fluorouracil, Leucovorin, Oxaliplatin, and Herceptin in the Treatment of Patients With Metastatic Colorectal Cancer Who Have Progressed After 5-FU and/or Irinotecan-Containing Therapy

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Response rate [ Time Frame: Every 2 tx cycles ] [ Designated as safety issue: No ]
  • Time to progression [ Time Frame: Every 2 tx cycles ] [ Designated as safety issue: No ]
  • Overall toxicity [ Time Frame: Each cycle during tx ] [ Designated as safety issue: Yes ]

Enrollment: 26
Study Start Date: May 2000
Study Completion Date: February 2003
Primary Completion Date: December 2002 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Combination Chemotx
Combination chemotherapy for metastatic colorectal cancer in patients who have disease progression after 5-FU and/or irinotecan-containing therapy
Biological: trastuzumab
4 mg/kg IV infusion Day 1, then weekly 2 mg/kg IV infusion (on Days 8, 15, & 22)
Other Name: Herceptin
Drug: fluorouracil
500 mg/sq m IV push weekly for 3 weeks, followed by a 1 wk break
Other Name: 5-FU
Drug: leucovorin calcium
500 mg/sq m IV infusion over 2 hours weekly for 3 weeks, then a 1 wk break
Drug: oxaliplatin
85 mg/sq m IV infusion over 2 hours Days 1 & 15 of each cycle

Detailed Description:

OBJECTIVES:

  • Determine the response rate of patients who overexpress HER-2/neu with metastatic colorectal adenocarcinoma who have progressed on at least 1 prior, but no more than 2 prior, chemotherapy regimens for metastatic colorectal cancer treated with fluorouracil, leucovorin calcium, oxaliplatin, and trastuzumab (Herceptin).
  • Determine the time to progression of these patients treated with this regimen.
  • Determine the overall toxicity of this regimen in these patients.

OUTLINE: Patients receive trastuzumab (Herceptin) IV over 30-90 minutes on days 1, 8, 15, and 22, followed by oxaliplatin IV over 2 hours on days 1 and 15, and then followed by leucovorin calcium IV over 2 hours on days 1, 8, and 15. Fluorouracil IV is administered at the midpoint of the leucovorin calcium infusion on days 1, 8, and 15. Treatment continues every 28 days in the absence of unacceptable toxicity or disease progression.

PROJECTED ACCRUAL: A total of 20-45 patients will be accrued for this study.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histologically confirmed advanced, recurrent, or metastatic colorectal adenocarcinoma
  • Resected CNS metastases stable greater than 1 month after completion of radiotherapy for CNS metastases eligible

    • No existing CNS metastases allowed
  • Measurable disease

    • At least 1 dimension as at least 20 mm with conventional techniques OR
    • At least 10 mm with spiral CT scan
    • No truly nonmeasurable lesions:

      • Bone lesions
      • Leptomeningeal disease
      • Lymphangitis cutis/pulmonis
      • Abdominal masses not confirmed and followed by imaging techniques
      • Cystic lesions
  • Must have progressed on at least 1 prior, but no more than 2 prior, fluorouracil and/or irinotecan containing treatment regimens for metastatic colorectal cancer
  • Must have documented HER-2/neu overexpression by immunohistochemistry staining

    • Staining score at least 2+

PATIENT CHARACTERISTICS:

Age:

  • 18 and over

Performance status:

  • ECOG 0-2

Life expectancy:

  • Not specified

Hematopoietic:

  • Granulocyte count at least 1,500/mm3
  • Platelet count at least 100,000/mm3

Hepatic:

  • Bilirubin no greater than 2.0 mg/dL
  • AST no greater than 2.5 times upper limit of normal

Renal:

  • Creatinine normal OR
  • Creatinine clearance at least 60 mL/min

Cardiovascular:

  • No history of cardiac ischemia or congestive heart failure
  • LVEF at least 50% by ECG or MUGA

Other:

  • Not pregnant or nursing
  • Fertile patients must use effective contraception
  • No concurrent second malignancy except nonmelanoma skin cancers or carcinoma in situ of the cervix unless completed therapy and considered to be at less than 30% risk of relapse

PRIOR CONCURRENT THERAPY:

Biologic therapy:

  • Not specified

Chemotherapy:

  • See Disease Characteristics
  • No prior platinum containing chemotherapy
  • At least 3 weeks since prior chemotherapy and recovered
  • No other concurrent chemotherapy

Endocrine therapy:

  • Not specified

Radiotherapy:

  • At least 3 weeks since prior radiotherapy and recovered

Surgery:

  • Not specified
  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: NCT00006015

  Hide Study Locations
Locations
United States, Alabama
Veterans Affairs Medical Center - Birmingham
Birmingham, Alabama, United States, 35233-1996
United States, California
University of California San Diego Cancer Center
La Jolla, California, United States, 92093-0658
UCSF Cancer Center and Cancer Research Institute
San Francisco, California, United States, 94143-0128
Veterans Affairs Medical Center - San Francisco
San Francisco, California, United States, 94121
United States, Delaware
CCOP - Christiana Care Health Services
Wilmington, Delaware, United States, 19899
United States, District of Columbia
Lombardi Cancer Center
Washington, District of Columbia, United States, 20007
Walter Reed Army Medical Center
Washington, District of Columbia, United States, 20307-5000
United States, Florida
CCOP - Mount Sinai Medical Center
Miami Beach, Florida, United States, 33140
United States, Illinois
University of Chicago Cancer Research Center
Chicago, Illinois, United States, 60637-1470
Veterans Affairs Medical Center - Chicago (Westside Hospital)
Chicago, Illinois, United States, 60612
United States, Iowa
Hematology Oncology Associates of the Quad Cities
Bettendorf, Iowa, United States, 52722
Holden Comprehensive Cancer Center
Iowa City, Iowa, United States, 52242-1009
United States, Maine
Veterans Affairs Medical Center - Togus
Togus, Maine, United States, 04330
United States, Maryland
Marlene and Stewart Greenebaum Cancer Center, University of Maryland
Baltimore, Maryland, United States, 21201
United States, Massachusetts
Massachusetts General Hospital Cancer Center
Boston, Massachusetts, United States, 02114
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02115
University of Massachusetts Memorial Medical Center - University Campus
Worcester, Massachusetts, United States, 01655
United States, Minnesota
University of Minnesota Cancer Center
Minneapolis, Minnesota, United States, 55455
Veterans Affairs Medical Center - Minneapolis
Minneapolis, Minnesota, United States, 55417
United States, Missouri
Ellis Fischel Cancer Center - Columbia
Columbia, Missouri, United States, 65203
Veterans Affairs Medical Center - Columbia (Truman Memorial)
Columbia, Missouri, United States, 65201
Barnes-Jewish Hospital
Saint Louis, Missouri, United States, 63110
United States, Nebraska
University of Nebraska Medical Center
Omaha, Nebraska, United States, 68198-7680
United States, Nevada
CCOP - Southern Nevada Cancer Research Foundation
Las Vegas, Nevada, United States, 89106
United States, New Hampshire
Norris Cotton Cancer Center
Lebanon, New Hampshire, United States, 03756-0002
United States, New York
Roswell Park Cancer Institute
Buffalo, New York, United States, 14263-0001
Veterans Affairs Medical Center - Buffalo
Buffalo, New York, United States, 14215
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10021
Mount Sinai Medical Center, NY
New York, New York, United States, 10029
New York Presbyterian Hospital - Cornell Campus
New York, New York, United States, 10021
CCOP - Syracuse Hematology-Oncology Associates of Central New York, P.C.
Syracuse, New York, United States, 13217
State University of New York - Upstate Medical University
Syracuse, New York, United States, 13210
Veterans Affairs Medical Center - Syracuse
Syracuse, New York, United States, 13210
United States, North Carolina
Lineberger Comprehensive Cancer Center, UNC
Chapel Hill, North Carolina, United States, 27599-7295
Duke Comprehensive Cancer Center
Durham, North Carolina, United States, 27710
Veterans Affairs Medical Center - Durham
Durham, North Carolina, United States, 27705
Comprehensive Cancer Center at Wake Forest University
Winston-Salem, North Carolina, United States, 27157-1082
CCOP - Southeast Cancer Control Consortium
Winston-Salem, North Carolina, United States, 27104-4241
United States, Ohio
Arthur G. James Cancer Hospital - Ohio State University
Columbus, Ohio, United States, 43210-1240
United States, Rhode Island
Rhode Island Hospital
Providence, Rhode Island, United States, 02903
United States, Tennessee
University of Tennessee Cancer Institute
Memphis, Tennessee, United States, 38103
Veterans Affairs Medical Center - Memphis
Memphis, Tennessee, United States, 38104
United States, Vermont
Green Mountain Oncology Group
Bennington, Vermont, United States, 05201
Vermont Cancer Center
Burlington, Vermont, United States, 05401-3498
Veterans Affairs Medical Center - White River Junction
White River Junction, Vermont, United States, 05009
United States, Virginia
MBCCOP - Massey Cancer Center
Richmond, Virginia, United States, 23298-0037
Veterans Affairs Medical Center - Richmond
Richmond, Virginia, United States, 23249
Sponsors and Collaborators
Investigators
Study Chair: Jeffrey W. Clark, MD Massachusetts General Hospital
  More Information

Publications:
Clark JW, Niedzwiecki D, Hollis D, et al.: Phase II trial of 5-fluororuacil (5-FU), leucovorin (LV), oxaliplatin (Ox), and trastuzamab (T) for patients with metastatic colorectal cancer (CRC) refractory to initial therapy. [Abstract] Proceedings of the American Society of Clinical Oncology 22: A-3584, 2003.

Responsible Party: Monica M Bertagnolli, Cancer and Leukemia Group B
ClinicalTrials.gov Identifier: NCT00006015     History of Changes
Other Study ID Numbers: CDR0000068024, U10CA031946, CALGB-89902
Study First Received: July 5, 2000
Last Updated: May 1, 2013
Health Authority: United States: Federal Government

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

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

ClinicalTrials.gov processed this record on September 22, 2014