Combination Chemotherapy in Treating Patients With Colorectal Cancer

This study has been completed.
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Alliance for Clinical Trials in Oncology
ClinicalTrials.gov Identifier:
NCT00006103
First received: August 3, 2000
Last updated: July 1, 2016
Last verified: July 2016
  Purpose

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. It is not yet known if the effectiveness of irinotecan combined with fluorouracil in treating colorectal cancer varies depending on the patient's racial background.

PURPOSE: Phase III trial to study the effectiveness of irinotecan combined with fluorouracil in treating patients from different racial backgrounds who have colorectal cancer that is advanced, recurrent, metastatic or has not responded to treatment with fluorouracil.


Condition Intervention Phase
Colorectal Cancer
Drug: fluorouracil
Drug: irinotecan hydrochloride
Drug: leucovorin calcium
Phase 3

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Interracial Study of CPT-11 (Irinotecan) Pharmacokinetics in 5-Fluorouracil Refractory Colorectal Cancer: A Population Pharmacokinetic/Pharmacodynamic Study of CPT-11

Resource links provided by NLM:


Further study details as provided by Alliance for Clinical Trials in Oncology:

Primary Outcome Measures:
  • overall survival [ Time Frame: Up to 10 years ]

Enrollment: 400
Study Start Date: July 2000
Study Completion Date: April 2002
Primary Completion Date: April 2002 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: irinotecan + leucovorin + fluorouracil

Patients receive irinotecan IV over 90 minutes, leucovorin calcium IV, and fluorouracil IV on days 1, 8, 15, and 22. Treatment repeats every 6 weeks for a total of 5 courses in the absence of disease progression or unacceptable toxicity.

Patients are followed every 3 months for 1 year and then every 6 months thereafter.

Drug: fluorouracil Drug: irinotecan hydrochloride Drug: leucovorin calcium

Detailed Description:

OBJECTIVES:

  • Determine the interracial differences in the pharmacokinetics of irinotecan in combination with fluorouracil in terms of SN-38 glucuronidation and biliary index, and gastrointestinal (GI) toxicity in patients with metastatic, locally advanced, or recurrent colorectal cancer.
  • Determine if there is a significant relationship between UGT1A1 genotype (promoter and/or coding region mutation) and CYP3A4 promoter genotype, vs GI toxicity, bone marrow toxicity, and pharmacokinetics of irinotecan in this patient population.

OUTLINE: Patients are stratified according to race (Asian or Pacific Islander vs black vs Hispanic vs white).

Patients receive irinotecan IV over 90 minutes, leucovorin calcium IV, and fluorouracil IV on days 1, 8, 15, and 22. Treatment repeats every 6 weeks for a total of 5 courses in the absence of disease progression or unacceptable toxicity.

Patients are followed every 3 months for 1 year and then every 6 months thereafter.

PROJECTED ACCRUAL: A total of 400 patients (100 per stratum) will be accrued for this study within 3 years.

  Eligibility

Ages Eligible for Study:   Child, Adult, Senior
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histologically confirmed adenocarcinoma of the colon or rectum

    • Metastatic, locally advanced, or recurrent disease
  • Patients must have at least 2 generations (parents and grandparents) who belong to one of the following racial groups:

    • Asian or Pacific Islander (e.g., China, Japan, Korea, the Philippine Islands, or Samoa)
    • Black (originating from the black racial groups of Africa)
    • Hispanic (originating from Mexico, Puerto Rico, Cuba, Central or South America, or other Spanish culture)
    • White (originating from the peoples of Europe, North Africa, or the Middle East)
  • No patients with parents or grandparents of mixed race or race other than that of the patient

PATIENT CHARACTERISTICS:

Age:

  • Not specified

Performance status:

  • CTC 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 1.5 mg/dL
  • AST no greater than 3 times upper limit of normal

Renal:

  • Creatinine no greater than 1.5 mg/dL

Other:

  • Not pregnant or nursing
  • Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

  • Not specified

Chemotherapy:

  • Prior adjuvant fluorouracil allowed if relapse occurred at least 6 months after completion of fluorouracil
  • At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin)
  • No prior irinotecan
  • No other concurrent chemotherapy

Endocrine therapy:

  • No concurrent hormones except steroids for adrenal failure, hormones for nondisease related conditions (e.g., insulin for diabetes), or intermittent dexamethasone as an antiemetic
  • No concurrent prednisone

Radiotherapy:

  • At least 4 weeks since prior radiotherapy (except to bone or soft tissue involving less than 25% of bone marrow)
  • No concurrent radiotherapy

Surgery:

  • At least 4 weeks since prior major surgery

Other:

  • No concurrent phenobarbital, valproate, or cyclosporine
  • None of the following concurrently during first course of therapy:

    • Macrolide antibiotics (e.g., azithromycin, erythromycin, clarithromycin, troleandomycin, dapsone)
    • Azole antibiotics (e.g., fuconazole, miconazole, itraconazole, ketoconazole)
    • Triazobenzodiazepines (e.g., alprazolam, midazolam, triazolam)
    • Antidepressants (e.g., fluoxetine, setraline hydrochloride, fluoxamine, nefazodone hydrochloride)
    • Quinolone antimicrobials (e.g., ciprofloxacin, ofloxacin)
    • Imidazole antibiotics (e.g., clotrimazole)
    • Anti-ulcer medications (e.g., omeprazole, lansoprazole)
    • Ethinyl estradiol
    • Diltiazem
    • Cimetidine hydrochloride
    • Cisapride
    • Terfenadine
    • Rifampin
    • Glucocorticoids
    • Antiepileptics
    • Grapefruit juice
  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: NCT00006103

Sponsors and Collaborators
Alliance for Clinical Trials in Oncology
National Cancer Institute (NCI)
Investigators
Study Chair: Brian Leyland-Jones, MD McGill Cancer Centre at McGill University
  More Information

Responsible Party: Alliance for Clinical Trials in Oncology
ClinicalTrials.gov Identifier: NCT00006103     History of Changes
Other Study ID Numbers: CALGB-9864  U10CA031946  CLB-9864  E-C9864  CDR0000068113 
Study First Received: August 3, 2000
Last Updated: July 1, 2016
Health Authority: United States: Federal Government

Keywords provided by Alliance for Clinical Trials in Oncology:
stage III colon cancer
stage IV colon cancer
stage III rectal cancer
stage IV rectal cancer
recurrent colon cancer
recurrent rectal cancer
adenocarcinoma of the colon
adenocarcinoma of the rectum

Additional relevant MeSH terms:
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Irinotecan
Camptothecin
Fluorouracil
Levoleucovorin
Leucovorin
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antimetabolites
Antimetabolites, Antineoplastic
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antidotes
Protective Agents
Vitamin B Complex

ClinicalTrials.gov processed this record on August 30, 2016