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

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

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.

Study Overview

• Status: Terminated
• Conditions: Colorectal Cancer
• Intervention / Treatment: Biological: trastuzumab; Drug: fluorouracil; Drug: leucovorin calcium; Drug: oxaliplatin

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.

• Study Type: Interventional
• Enrollment (Actual): 26
• Phase: Phase 2

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

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 Names: Herceptin; Drug: fluorouracil; 500 mg/sq m IV push weekly for 3 weeks, followed by a 1 wk break; Other Names: 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Response rate	Every 2 tx cycles
Time to progression	Every 2 tx cycles
Overall toxicity	Each cycle during tx

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Investigators: Study Chair: Jeffrey W. Clark, MD, Massachusetts General Hospital

Publications and helpful links

General 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.

Study record dates

Study Major Dates

• Study Start: May 1, 2000
• Primary Completion (Actual): December 1, 2002
• Study Completion (Actual): February 1, 2003

Study Registration Dates

• First Submitted: July 5, 2000
• First Submitted That Met QC Criteria: January 26, 2003
• First Posted (Estimate): January 27, 2003

Study Record Updates

• Last Update Posted (Estimate): May 3, 2013
• Last Update Submitted That Met QC Criteria: May 1, 2013
• Last Verified: June 1, 2011

More Information

Terms related to this study

• Keywords: adenocarcinoma of the rectum; stage IV rectal cancer; stage IV colon cancer; adenocarcinoma of the colon; recurrent colon cancer; recurrent rectal cancer
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Protective Agents; Antineoplastic Agents, Immunological; Micronutrients; Vitamins; Calcium-Regulating Hormones and Agents; Antidotes; Vitamin B Complex; Trastuzumab; Fluorouracil; Oxaliplatin; Leucovorin; Calcium; Levoleucovorin
• Other Study ID Numbers: CDR0000068024; U10CA031946 (U.S. NIH Grant/Contract); CALGB-89902