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

Phase II Study in Patients With Metastatic Colorectal Carcinoma Previously Treated With Oxaliplatin (OXAL) or a Combination of Irinotecan (CPT-11) and OXAL

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.

Study Overview

• Status: Completed
• Conditions: Colorectal Cancer
• Intervention / Treatment: Drug: fluorouracil; Drug: leucovorin calcium; Drug: irinotecan hydrochloride

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 19
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Saskatchewan
    • Regina, Saskatchewan, Canada, S4T 7T1
      • Allan Blair Cancer Centre
• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85259-5404
      • CCOP - Scottsdale Oncology Program
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic
  • Illinois
    • Peoria, Illinois, United States, 61602
      • CCOP - Illinois Oncology Research Association
    • Urbana, Illinois, United States, 61801
      • CCOP - Carle Cancer Center
  • Iowa
    • Cedar Rapids, Iowa, United States, 52403-1206
      • CCOP - Cedar Rapids Oncology Project
    • Des Moines, Iowa, United States, 50309-1016
      • CCOP - Iowa Oncology Research Association
    • Sioux City, Iowa, United States, 51101-1733
      • Siouxland Hematology-Oncology
  • Kansas
    • Wichita, Kansas, United States, 67214-3882
      • CCOP - Wichita
  • Michigan
    • Ann Arbor, Michigan, United States, 48106
      • CCOP - Ann Arbor Regional
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic Cancer Center
    • Saint Louis Park, Minnesota, United States, 55416
      • CCOP - Metro-Minnesota
  • Nebraska
    • Omaha, Nebraska, United States, 68106
      • CCOP - Missouri Valley Cancer Consortium
  • South Dakota
    • Rapid City, South Dakota, United States, 57709
      • Rapid City Regional Hospital
    • Sioux Falls, South Dakota, United States, 57104
      • CCOP - Sioux Community Cancer Consortium

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:

• 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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: irinotecan; 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.	Drug: irinotecan hydrochloride
Experimental: leucovorin + fluorouracil; 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.	Drug: fluorouracil; Drug: leucovorin calcium

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
tumor response rate	Up to 5 years

Secondary Outcome Measures

Outcome Measure	Time Frame
overall survival	Up to 5 years
quality of life	Up to 5 years
time to tumor progression	Up to 5 years
time to treatment failure	Up to 5 years

Collaborators and Investigators

• Sponsor: Alliance for Clinical Trials in Oncology
• Collaborators: National Cancer Institute (NCI)
• Investigators: Study Chair: Henry C. Pitot, MD, Mayo Clinic

Study record dates

Study Major Dates

• Study Start: April 1, 2001
• Primary Completion (Actual): April 1, 2004
• Study Completion (Actual): October 1, 2009

Study Registration Dates

• First Submitted: June 6, 2001
• First Submitted That Met QC Criteria: January 26, 2003
• First Posted (Estimate): January 27, 2003

Study Record Updates

• Last Update Posted (Estimate): December 7, 2016
• Last Update Submitted That Met QC Criteria: December 5, 2016
• Last Verified: December 1, 2016

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; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Protective Agents; Topoisomerase Inhibitors; Micronutrients; Vitamins; Calcium-Regulating Hormones and Agents; Topoisomerase I Inhibitors; Antidotes; Vitamin B Complex; Fluorouracil; Leucovorin; Irinotecan; Calcium; Levoleucovorin
• Other Study ID Numbers: NCCTG-N0048; NCI-2012-02383 (Registry Identifier: CTRP (Clinical Trials Reporting System)); CDR0000068635 (Registry Identifier: PDQ (Physician Data Query))