Irinotecan or Fluorouracil Plus Leucovorin in Treating Patients With Previously Treated Metastatic Colorectal Cancer

Alliance for Clinical Trials in Oncology

Status and phase: Completed; Phase 2

Conditions: Colorectal Cancer

Treatments: Drug: fluorouracil; Drug: leucovorin calcium; Drug: irinotecan hydrochloride

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00016952

NCI-2012-02383 (Registry Identifier)

NCCTG-N0048

CDR0000068635 (Registry Identifier)

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. Giving the drugs in different combinations may kill more tumor cells.

PURPOSE: Phase II trial to compare the effectiveness of either irinotecan or fluorouracil plus leucovorin in treating patients who have metastatic colorectal cancer that has been previously treated with oxaliplatin with or without irinotecan.

Full description

OBJECTIVES:

• Determine the tumor response rate in patients receiving irinotecan or fluorouracil and leucovorin calcium for metastatic colorectal cancer previously treated with oxaliplatin with or without irinotecan.
• Determine the time to tumor progression, time to treatment failure, and overall survival of patients treated with these regimens.
• Determine the toxic effects of these regimens in these patients.
• Evaluate the quality of life of patients treated with these regimens.

OUTLINE: This is a multicenter study. Patients are stratified according to prior chemotherapy (oxaliplatin-based therapy vs irinotecan and oxaliplatin combination therapy). Patients are assigned to one of two treatment groups.

• Group I (prior oxaliplatin-based chemotherapy): Patients receive irinotecan IV over 90 minutes on day 1. Treatment repeats every 3 weeks.
• Group II (prior irinotecan and oxaliplatin combination chemotherapy): Patients receive leucovorin calcium IV over 2 hours and fluorouracil IV continuously on days 1 and 2. Treatment repeats every 2 weeks.
• Both groups: Treatment continues in the absence of disease progression or unacceptable toxicity. Patients with a confirmed complete response for 2 consecutive courses may discontinue treatment at investigator's discretion.

Quality of life is assessed at baseline, approximately every 6 weeks during treatment, and then after the last course of treatment.

Patients are followed every 3 months for 5 years.

Enrollment: 19 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

• Diagnosis of metastatic colorectal adenocarcinoma incurable by surgery or not amenable to radiotherapy with curative intent

• Progressive disease after one of the following prior treatments for metastatic disease:

  • Oxaliplatin-based chemotherapy
  • Irinotecan and oxaliplatin combination chemotherapy

• At least 1 measurable lesion

  • At least 20 mm in at least one dimension

• No known CNS metastases or carcinomatous meningitis

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• ECOG 0-2

Life expectancy:

• At least 12 weeks

Hematopoietic:

• Absolute neutrophil count at least 2,000/mm^3
• Platelet count at least 100,000/mm^3

Hepatic:

• Bilirubin no greater than 0.5 mg/dL above upper limit of normal (ULN)
• AST no greater than 5 times ULN

Renal:

• Creatinine no greater than 1.5 times ULN

Cardiovascular:

• No unstable angina
• No symptomatic congestive heart failure
• No serious uncontrolled cardiac arrhythmia

Other:

• No active or uncontrolled infection
• No evidence of other serious illness
• No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer or noninvasive carcinomas
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• No concurrent sargramostim (GM-CSF)

Chemotherapy:

• See Disease Characteristics
• At least 4 weeks since prior chemotherapy
• No more than 1 prior chemotherapy regimen for advanced colorectal cancer
• Prior adjuvant chemotherapy allowed

Endocrine therapy:

• Not specified

Radiotherapy:

• See Disease Characteristics
• No prior radiotherapy to more than 25% of bone marrow

Surgery:

• See Disease Characteristics
• At least 4 weeks since prior major surgery

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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19 participants in 2 patient groups

irinotecan

Experimental group

Description:

Prior oxaliplatin-based chemotherapy: Patients receive irinotecan IV over 90 minutes on day 1. Treatment repeats every 3 weeks. Treatment continues in the absence of disease progression or unacceptable toxicity. Patients with a confirmed complete response for 2 consecutive courses may discontinue treatment at investigator's discretion. Quality of life is assessed at baseline, approximately every 6 weeks during treatment, and then after the last course of treatment. Patients are followed every 3 months for 5 years.

Treatment:

Drug: irinotecan hydrochloride

leucovorin + fluorouracil

Experimental group

Description:

Prior to irinotecan and oxaliplatin combination chemotherapy: Patients receive leucovorin calcium IV over 2 hours and fluorouracil IV continuously on days 1 and 2. Treatment repeats every 2 weeks. Treatment continues in the absence of disease progression or unacceptable toxicity. Patients with a confirmed complete response for 2 consecutive courses may discontinue treatment at investigator's discretion. Quality of life is assessed at baseline, approximately every 6 weeks during treatment, and then after the last course of treatment. Patients are followed every 3 months for 5 years.

Treatment:

Drug: leucovorin calcium

Drug: fluorouracil