Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Trial Contact Information
Registry Information

Alternate Title

Combination Chemotherapy in Treating Patients With Colorectal Cancer

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase III Treatment Completed Not specified NCI CLB-9864 E-C9864, NCT00006103, C9864

Objectives

1. 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.
2. 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.

Entry 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

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

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

Expected Enrollment

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

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.

Trial Contact Information

Trial Lead Organizations

Cancer and Leukemia Group B

Brian Leyland-Jones, MD, Protocol chair(Contact information may not be current)		Ph: 514-398-8986 Email: brian.leyland-jones@mcgill.ca

Eastern Cooperative Oncology Group

Sridhar Mani, MD, Protocol chair		Ph: 718-904-2488 Email: smani@montefiore.org

Registry Information
Official Title		Interracial Study of CPT-11 (Irinotecan) Pharmacokinetics in 5-Fluorouracil Refractory Colorectal Cancer: A Population Pharmacokinetic/Pharmacodynamic Study of CPT-11
Trial Start Date		2000-07-15
Registered in ClinicalTrials.gov		NCT00006103
Date Submitted to PDQ		2000-06-28
Information Last Verified		2007-02-08
NCI Grant/Contract Number		CA31946