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Interracial Study of CPT-11 (Irinotecan) Pharmacokinetics in 5-Fluorouracil Refractory Colorectal Cancer: A Population Pharmacokinetic/Pharmacodynamic Study of CPT-11


Phase 3
N/A
N/A
Not Enrolling
Both
Colorectal Cancer

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Trial Information

Interracial Study of CPT-11 (Irinotecan) Pharmacokinetics in 5-Fluorouracil Refractory Colorectal Cancer: A Population Pharmacokinetic/Pharmacodynamic Study of CPT-11


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.

Inclusion 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

Type of Study:

Interventional

Study Design:

Primary Purpose: Treatment

Principal Investigator

Brian Leyland-Jones, MD

Investigator Role:

Study Chair

Investigator Affiliation:

McGill Cancer Centre at McGill University

Authority:

United States: Federal Government

Study ID:

CDR0000068113

NCT ID:

NCT00006103

Start Date:

July 2000

Completion Date:

Related Keywords:

  • Colorectal Cancer
  • 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
  • Colorectal Neoplasms

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