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

National Cancer Institute (NCI)

Status and phase: Terminated; Phase 2

Conditions: Colorectal Cancer

Treatments: Drug: fluorouracil; Drug: leucovorin calcium; Drug: oxaliplatin; Biological: trastuzumab

Study type: Interventional

Funder types: NIH

Identifiers

NCT00006015

CALGB-89902

CDR0000068024

U10CA031946 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 26 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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26 participants in 1 patient group

Combination Chemotx

Experimental group

Description:

Combination chemotherapy for metastatic colorectal cancer in patients who have disease progression after 5-FU and/or irinotecan-containing therapy

Treatment:

Biological: trastuzumab

Drug: oxaliplatin

Drug: leucovorin calcium

Drug: fluorouracil