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

  Show 47 Study Locations
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
Fluorouracil
Oxaliplatin
Trastuzumab
Leucovorin
Levoleucovorin
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antimetabolites, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Vitamin B Complex
Vitamins
Micronutrients
Growth Substances
Antidotes

ClinicalTrials.gov processed this record on July 24, 2014