Irinotecan and Cyclosporine in Treating Patients With Metastatic, Advanced or Locally Recurrent Colorectal Cancer

A Phase II Trial of Irinotecan (CPT-11) and Cyclosporine in Patients With 5-FU Refractory Advanced Colorectal Cancer

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.

Study Overview

• Status: Completed
• Conditions: Colorectal Cancer
• Intervention / Treatment: Drug: cyclosporine; Drug: CPT-11

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.

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60612
      • University of Illinois at Chicago
    • Chicago, Illinois, United States, 60640
      • Louis A. Weiss Memorial Hospital
    • Chicago, Illinois, United States, 60637
      • University of Chicago Cancer Research Center
    • Decatur, Illinois, United States, 62526
      • Cancer Care Specialists of Central Illinois, S.C.
    • Evanston, Illinois, United States, 60201
      • Evanston Northwestern Health Care
    • Park Ridge, Illinois, United States, 60068
      • Division of Hematology/Oncology
    • Peoria, Illinois, United States, 61602
      • Oncology/Hematology Associates of Central Illinois, P.C.
    • Springfield, Illinois, United States, 62701
      • Central Illinois Hematology Oncology Center
  • Indiana
    • Fort Wayne, Indiana, United States, 46885-5099
      • Fort Wayne Medical Oncology and Hematology, Inc.
    • South Bend, Indiana, United States, 46617
      • Michiana Hematology/Oncology P.C.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CPT-11 with Cyclosporine; Each cycle lasts 6 weeks. Administration of cyclosporine and CPT-11 weekly for 4 weeks followed by a 2 week 'rest' period with no drug given. Cyclosporine is given by IV infusion at a dose of 5 mg/kg. CPT-11 is given by IV infusion at a dose of 60 mg/m2.	Drug: cyclosporine; Other Names: Sandimmune®, Restatis®; Drug: CPT-11; Other Names: Irinotecan, Camptosar®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Reduction in occurrences of severe diarrhea due to CPT-11 administration	12 weeks

Collaborators and Investigators

• Sponsor: University of Chicago
• Collaborators: National Cancer Institute (NCI)

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: January 1, 2000
• Primary Completion (Actual): December 1, 2001
• Study Completion (Actual): January 1, 2005

Study Registration Dates

• First Submitted: November 1, 1999
• First Submitted That Met QC Criteria: April 26, 2004
• First Posted (Estimate): April 27, 2004

Study Record Updates

• Last Update Posted (Estimate): March 7, 2014
• Last Update Submitted That Met QC Criteria: March 6, 2014
• Last Verified: March 1, 2014

More Information

Terms related to this study

• Keywords: adenocarcinoma of the rectum; stage IV rectal cancer; stage IV colon cancer; adenocarcinoma of the colon; recurrent colon cancer; recurrent rectal cancer
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Topoisomerase Inhibitors; Dermatologic Agents; Antifungal Agents; Topoisomerase I Inhibitors; Calcineurin Inhibitors; Irinotecan; Cyclosporine; Cyclosporins
• Other Study ID Numbers: 9824 (CTEP); UCCRC-T98-0049; NCI-T98-0049