Irinotecan Compared With Combination Chemotherapy in Treating Patients With Advanced Colorectal Cancer

This study has been completed.
Sponsor:
Collaborators:
Southwest Oncology Group
Eastern Cooperative Oncology Group
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00005036
First received: April 6, 2000
Last updated: May 1, 2013
Last verified: May 2013
  Purpose

Randomized phase III trial to compare the effectiveness of irinotecan with that of combination chemotherapy in treating patients who have advanced colorectal cancer that has not responded to previous treatment. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells. It is not yet known which chemotherapy regimen is more effective for colorectal cancer.


Condition Intervention Phase
Mucinous Adenocarcinoma of the Colon
Mucinous Adenocarcinoma of the Rectum
Recurrent Colon Cancer
Recurrent Rectal Cancer
Signet Ring Adenocarcinoma of the Colon
Signet Ring Adenocarcinoma of the Rectum
Stage IIIA Colon Cancer
Stage IIIA Rectal Cancer
Stage IIIB Colon Cancer
Stage IIIB Rectal Cancer
Stage IIIC Colon Cancer
Stage IIIC Rectal Cancer
Stage IVA Colon Cancer
Stage IVA Rectal Cancer
Stage IVB Colon Cancer
Stage IVB Rectal Cancer
Drug: irinotecan hydrochloride
Drug: oxaliplatin
Drug: leucovorin calcium
Drug: fluorouracil
Procedure: quality-of-life assessment
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomized Phase III Equivalence Trial of Irinotecan (CPT-11) Versus Oxaliplatin (OXAL)/5-Fluorouracil (5-FU)/Leucovorin (CF) in Patients With Advanced Colorectal Carcinoma Previously Treated With 5-FU

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Overall survival [ Time Frame: At least 6 months ] [ Designated as safety issue: No ]
    The primary analysis for this trial will be based on a one-sided Generalized Wilcoxon test.


Secondary Outcome Measures:
  • Time-to-tumor progression [ Time Frame: Time from start of therapy to documentation of disease progression, assessed up to 3 years ] [ Designated as safety issue: No ]
  • Time-to-treatment failure [ Time Frame: Time from the date of randomization to the date at which the patient is removed from treatment due to progression, toxicity, refusal, or death, assessed up to 3 years ] [ Designated as safety issue: No ]
  • Objective tumor response rate (CR or PR) in patients with measureable disease [ Time Frame: At least 4 weeks ] [ Designated as safety issue: No ]
  • Toxicity and dose intensity [ Time Frame: Up to 3 years ] [ Designated as safety issue: Yes ]
  • Quality of life [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]

Enrollment: 560
Study Start Date: November 1999
Primary Completion Date: December 2006 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I (irinotecan)
Patients receive irinotecan IV over 90 minutes on day 1. Treatment repeats every 3 weeks in the absence of disease progression or unacceptable toxicity.
Drug: irinotecan hydrochloride
Given IV
Other Names:
  • Campto
  • Camptosar
  • CPT-11
  • irinotecan
  • U-101440E
Procedure: quality-of-life assessment
Ancillary studies
Other Name: quality of life assessment
Experimental: Arm II (oxalipatin, fluorouracil, leucovorin calcium)
Patients receive oxaliplatin IV over 2 hours on day 1, leucovorin calcium IV over 2 hours on days 1 and 2, and fluorouracil IV bolus followed by IV infusion over 22 hours on days 1 and 2. Treatment repeats every 2 weeks in the absence of disease progression or unacceptable toxicity.
Drug: oxaliplatin
Given IV
Other Names:
  • 1-OHP
  • Dacotin
  • Dacplat
  • Eloxatin
  • L-OHP
Drug: leucovorin calcium
Given IV
Other Names:
  • CF
  • CFR
  • LV
Drug: fluorouracil
Given IV
Other Names:
  • 5-fluorouracil
  • 5-Fluracil
  • 5-FU
Procedure: quality-of-life assessment
Ancillary studies
Other Name: quality of life assessment

Detailed Description:

PRIMARY OBJECTIVES:

I. Determine whether in advanced colorectal carcinoma patients who have been previously treated with 5-FU, the overall survival of patients treated with OXAL + 5-FU + CF followed by CPT-11 is equivalent to the survival of patients treated with CPT-11 followed by OXAL + 5-FU + CF.

SECONDARY OBJECTIVES:

I. Evaluation of time to tumor progression, time to treatment failure, toxicity of treatment, and overall response rate in patients treated with these two regimens.

II. To compare quality-of-life measurements patients treated with these two regimens.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to performance status (ECOG 0-1 vs 2), primary indicator lesion (hepatic vs pulmonary vs other), age (less than 65 vs at least 65 years), alkaline phosphatase (less than 2 vs at least 2 times ULN), fluorouracil failure (adjuvant vs metastatic), and membership (intergroup vs expanded participation project). Patients are randomized to one of two treatment arms.

ARM I: Patients receive irinotecan IV over 90 minutes on day 1. Treatment repeats every 3 weeks in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive oxaliplatin IV over 2 hours on day 1, leucovorin calcium IV over 2 hours on days 1 and 2, and fluorouracil IV bolus followed by IV infusion over 22 hours on days 1 and 2. Treatment repeats every 2 weeks in the absence of disease progression or unacceptable toxicity.

Patients who experience progression or toxicity on the initial regimen may crossover to the other regimen. At least 3 weeks must elapse between regimens.

Quality of life is assessed at baseline, prior to each chemotherapy course, at crossover, and at the end of the study.

Patients are followed every 6 months for 3 years or until death.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically or cytologically confirmed locally advanced, locally recurrent,or metastatic colorectal adenocarcinoma not curable by surgery or radiotherapy
  • Progressive disease following:

    • One prior fluorouracil based chemotherapy regimen for metastatic disease
    • Failure during or within 6 months after fluorouracil based adjuvant therapy
  • Measurable or evaluable disease
  • No CNS metastases or carcinomatous meningitis
  • Performance status - ECOG 0-2
  • At least 12 weeks
  • Absolute neutrophil count at least 1,500/mm^3
  • Platelet count at least 100,000/mm^3
  • Hemoglobin at least 9 g/dL (transfusion allowed)
  • Bilirubin no greater than 1.5 mg/dL
  • AST no greater than 5 times upper limit of normal (ULN)
  • Alkaline phosphatase no greater than 5 times ULN
  • Creatinine no greater than 1.5 times ULN
  • No uncontrolled high blood pressure
  • No unstable angina
  • No symptomatic congestive heart failure
  • No myocardial infarction with the past 6 months
  • No serious uncontrolled cardiac arrhythmias
  • No New York Heart Association class III or IV heart disease
  • No pleural effusion or ascites that cause respiratory compromise (e.g., dyspnea grade 2 or greater)
  • No interstitial pneumonia or extensive and symptomatic interstitial fibrosis of the lung
  • Not pregnant or nursing
  • Fertile patients must use effective contraception
  • Fluent in English
  • No active or uncontrolled infection
  • No other prior malignancy within the past 5 years, except:
  • Adequately treated basal or squamous cell skin cancer
  • Adequately treated noninvasive carcinomas
  • No sensory neuropathy grade 2 or greater
  • No uncontrolled colonic or small bowel disorders (greater than 3 loose stools daily)
  • No concurrent sargramostim (GM-CSF)
  • At least 4 weeks since prior chemotherapy and recovered
  • No more than 1 prior chemotherapy regimen for advanced colorectal cancer
  • No prior irinotecan or other camptothecin derivative (e.g., topotecan)
  • No prior oxaliplatin
  • No other concurrent investigational chemotherapy agents
  • At least 4 weeks since prior major radiotherapy
  • No prior radiotherapy to greater than 25% of bone marrow
  • At least 4 weeks since prior major surgery and recovered
  • At least 2 weeks since prior minor surgery and recovered
  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: NCT00005036

Locations
United States, Minnesota
North Central Cancer Treatment Group
Rochester, Minnesota, United States, 55905
Sponsors and Collaborators
Southwest Oncology Group
Eastern Cooperative Oncology Group
Investigators
Principal Investigator: Henry Pitot North Central Cancer Treatment Group
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00005036     History of Changes
Other Study ID Numbers: NCI-2012-01847, N9841, SWOG-N9841, NCCTG-N9841, CDR0000067623, ECOG-N9841, U10CA025224
Study First Received: April 6, 2000
Last Updated: May 1, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Adenocarcinoma
Colonic Neoplasms
Rectal Neoplasms
Adenocarcinoma, Mucinous
Cystadenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Neoplasms, Cystic, Mucinous, and Serous
Calcium, Dietary
Fluorouracil
Oxaliplatin
Irinotecan
Camptothecin
Leucovorin
Levoleucovorin
Bone Density Conservation Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 28, 2014