Basic Trial Information
Trial Description
     Summary
     Further Trial Information
     Eligibility Criteria
Trial Contact Information

Basic Trial Information

Trial Description

Summary

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug and combining chemotherapy with surgery may kill more tumor cells. It is not yet known if surgery is more effective with or without chemotherapy for liver metastases.

PURPOSE: Randomized phase III trial to compare the effectiveness of surgery with or without combination chemotherapy in treating patients who have liver metastases from colorectal cancer.

Further Study Information

OBJECTIVES:

• Compare the progression-free and overall survival of patients with resectable colorectal liver metastases treated with surgery with or without neoadjuvant and adjuvant oxaliplatin, fluorouracil, and leucovorin calcium.

• Compare the percentage of patients with total resection with these two treatments.

OUTLINE: This is a multicenter study. Patients are stratified according to participating center, prior adjuvant chemotherapy (yes vs no), plasma CEA level in ng/mL at diagnosis of liver metastases (5 or less vs 6 to 30 vs 31 or greater), serosa extension of primary cancer (absent T1 or T2 vs present T3 or T4), lymphatic spread of primary cancer (absent vs present N+), time interval between diagnosis of primary tumor to metastases (2 years or more vs fewer than 2 years), and number of metastases (1 to 3 vs 4). Patients are randomized to one of two treatment arms.

• Arm I: Patients receive oxaliplatin IV over 2 hours on day 1 and leucovorin calcium (LV) IV over 2 hours followed by fluorouracil (5-FU) IV over 22 hours on days 1 and 2. Treatment repeats every 15 days for 6 courses in the absence of disease progression or unacceptable toxicity.

At 2 to 5 weeks after chemotherapy, patients undergo liver resection. Patients with progressive disease after 3 courses of chemotherapy undergo liver resection at least 2 weeks after completion of course 3 and do not receive postoperative chemotherapy.

At 2 to 5 weeks after surgery, patients receive oxaliplatin, LV, and 5-FU as in preoperative chemotherapy.

• Arm II: Patients undergo liver resection. Patients are followed every 3 months for 2 years and then every 6 months thereafter.

Peer Reviewed and Funded or Endorsed by Cancer Research UK

PROJECTED ACCRUAL: A total of 330 patients (165 per arm) will be accrued for this study within 3 years.

Eligibility Criteria

DISEASE CHARACTERISTICS:

• Diagnosis of potentially resectable colorectal liver metastases that meets one of the following criteria:

• Metachronous metastases after complete resection of primary tumor without gross or microscopic evidence of residual disease

• Synchronous metastases after complete resection of primary tumor more than 1 month before study

• Synchronous metastases with sufficient evidence (i.e., CAT scan or diagnostic laparoscopy) that both the primary tumor and liver metastases can be completely resected during the same procedure and resection of primary may be delayed 3-4 months

PATIENT CHARACTERISTICS:

Age:

• 18 to 80

Performance status:

• WHO 0-2

• Karnofsky 60-100%

Life expectancy:

• Not specified

Hematopoietic:

• Absolute neutrophil count greater than 1,500/mm^3

• Platelet count greater than 100,000/mm^3

Hepatic:

• No hepatic insufficiency

Renal:

• Creatinine less than 2 times upper limit of normal

Cardiovascular:

• No uncontrolled congestive heart failure or angina pectoris

• No hypertension or arrhythmia

Other:

• No other malignancy within the past 10 years except adequately treated carcinoma in situ of the cervix or nonmelanoma skin cancer

• No peripheral neuropathy greater than grade 1

• No prior significant neurologic or psychiatric disorders

• No active infection

• Not pregnant or nursing

• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• No concurrent biologic therapy

Chemotherapy:

• No prior chemotherapy for advanced disease

• Prior adjuvant chemotherapy for primary cancer allowed unless included oxaliplatin

• No other concurrent chemotherapy

Endocrine therapy:

• No concurrent anticancer endocrine therapy

Radiotherapy:

• No concurrent radiotherapy

Surgery:

• See Disease Characteristics

Other:

• At least 30 days since prior investigational drugs

• No concurrent investigational drugs

Trial Contact Information

Trial Lead Organizations/Sponsors

European Organization for Research and Treatment of Cancer

Bernard Nordlinger

Euan T. Walpole, MD

Study Chair

Wolf O. Bechstein

Study Chair

John N. Primrose

Study Chair

Philippe Rougier

Study Chair

Link to the current ClinicalTrials.gov record.
NLM Identifer NCT00006479
Information obtained from ClinicalTrials.gov on January 10, 2012

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