Clinical trial NCT00003950: Irinotecan and Cyclosporine in Treating Patients With Metastatic, Advanced or Locally Recurrent Colorectal Cancer
Official title: A Phase II Trial of Irinotecan (CPT-11) and Cyclosporine in Patients With 5-FU Refractory Advanced Colorectal Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Colorectal Cancer
Keywords: stage IV colon cancer
stage IV rectal cancer
recurrent colon cancer
recurrent rectal cancer
adenocarcinoma of the colon
adenocarcinoma of the rectum
Lead sponsor: University of Chicago
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2004-04-27
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Cyclosporine may relieve the diarrhea caused by irinotecan.

PURPOSE: Phase II trial to study the effectiveness of irinotecan and cyclosporine in treating patients who have metastatic, advanced, or locally recurrent colorectal cancer that has not responded to fluorouracil.

Detailed description: OBJECTIVES: I. Determine the response rate of patients with metastatic, advanced, or locally recurrent fluorouracil refractory adenocarcinoma of the colon or rectum treated with irinotecan and cyclosporine. II. Determine antitumor activity, safety, tolerance, and toxicity of this combination treatment in these patients.

OUTLINE: This is a multicenter study. Patients receive cyclosporine IV over 6 hours and irinotecan IV over 90 minutes weekly for 4 weeks. Courses repeat every 6 weeks. Patients receive at least 2 courses in the absence of disease progression or unacceptable toxicity.

PROJECTED ACCRUAL: A total of 15-45 patients will be accrued for this study over 14 months.

Eligibility criteria: DISEASE CHARACTERISTICS: Histologically proven metastatic, advanced, or locally recurrent fluorouracil (5-FU) refractory adenocarcinoma of the colon or rectum Progression of disease within 6 months of receiving adjuvant 5-FU based chemotherapy OR Progression of disease during or following completion of 5-FU based chemotherapy for metastatic disease No more than 1 failure with a 5-FU regimen for recurrent, advanced, or metastatic disease Failure on 5-FU adjuvant therapy must accompany failure on 5-FU therapy for metastatic disease Bidimensionally measurable disease CNS metastases allowed only with measurable disease in other sites Prior treatment for CNS metastases required

PATIENT CHARACTERISTICS: Age: 18 and over Performance status: ECOG 0-2 Life expectancy: At least 12 weeks Hematopoietic: WBC at least 3500/mm3 Absolute neutrophil count at least 1500/mm3 Platelet count at least 100,000/mm3 Hepatic: Bilirubin no greater than 1.5 mg/dL AST and ALT no greater than 3 times upper limit of normal Renal: Creatinine no greater than 1.5 mg/dL OR Creatinine clearance at least 60 mL/min Other: No other significant, uncontrolled underlying medical or psychiatric condition No serious active infection Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception Neurologically stable No other prior malignancy within past 5 years except curatively treated nonmelanomatous skin cancer

PRIOR CONCURRENT THERAPY: Biologic therapy: No concurrent immunotherapy Chemotherapy: See Disease Characteristics Prior adjuvant fluorouracil (5-FU) allowed No more than 2 prior 5-FU regimens (no more than 1 for recurrent or metastatic disease) No other concurrent chemotherapy Endocrine therapy: No concurrent hormonal therapy (except contraceptives or replacement steroids) No concurrent IV steroids Radiotherapy: Prior radiotherapy allowed if measurable disease outside radiation port At least 4 weeks since prior radiotherapy and recovered No concurrent radiotherapy Surgery: Not specified Other: No concurrent anticonvulsant therapy No other concurrent experimental medications

Primary outcomes:
measure: Reduction in occurrences of severe diarrhea due to CPT-11 administration
timeFrame: 12 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Chicago
country: United States
facility: University of Illinois at Chicago
state: Illinois
city: Chicago
country: United States
facility: University of Chicago Cancer Research Center
state: Illinois
city: Chicago
country: United States
facility: Louis A. Weiss Memorial Hospital
state: Illinois
city: Decatur
country: United States
facility: Cancer Care Specialists of Central Illinois, S.C.
state: Illinois
city: Evanston
country: United States
facility: Evanston Northwestern Health Care
state: Illinois
city: Park Ridge
country: United States
facility: Division of Hematology/Oncology
state: Illinois
city: Peoria
country: United States
facility: Oncology/Hematology Associates of Central Illinois, P.C.
state: Illinois
city: Springfield
country: United States
facility: Central Illinois Hematology Oncology Center
state: Illinois
city: Fort Wayne
country: United States
facility: Fort Wayne Medical Oncology and Hematology, Inc.
state: Indiana
city: South Bend
country: United States
facility: Michiana Hematology/Oncology P.C.
state: Indiana
Study officials:
affiliation: University of Chicago
name: Hedy L. Kindler, MD
role: STUDY_CHAIR
References:
citation: Desai AA, Kindler HL, Taber D, Agamah E, Mani S, Wade-Oliver K, Ratain MJ, Vokes EE. Modulation of irinotecan with cyclosporine: a phase II trial in advanced colorectal cancer. Cancer Chemother Pharmacol. 2005 Oct;56(4):421-6. doi: 10.1007/s00280-005-1020-5. Epub 2005 May 13.