Amifostine Plus Irinotecan in Treating Patients With Metastatic Colorectal Cancer

Phase I/II Trial to Evaluate Ethyol as a Protective Agent for Irinotecan (CPT-11) Toxicities in Patients With Advanced Colorectal Cancer

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die.

PURPOSE: Phase I/II trial to study the effectiveness of amifostine plus irinotecan in treating patients with metastatic colorectal cancer.

Study Overview

• Status: Completed
• Conditions: Colorectal Cancer
• Intervention / Treatment: Drug: amifostine trihydrate; Drug: irinotecan hydrochloride

Detailed Description

OBJECTIVES: I. Assess the toxicity profile of irinotecan and amifostine when administered together in patients with metastatic colorectal cancer. II. Assess the total dose of irinotecan received per 6 week course in these patients. III. Determine the incidence of irinotecan-induced leukopenia, neutropenia, and diarrhea in these patients. V. Determine the response rate for this patient population.

OUTLINE: This is an open label study. Amifostine is administered by 10 minute IV infusions. Irinotecan is administered by IV infusions 15 minutes after completion of amifostine. Treatment is repeated every 2 weeks for 6 weeks. This 6 week course is repeated in the absence of disease progression. Treatment may be delayed up to 2 weeks after a course to allow for recovery from toxic effects. Patients are followed at the end of study and at 30 days after study.

PROJECTED ACCRUAL: There will be 25-30 patients accrued into this study.

• Study Type: Interventional
• Enrollment (Actual): 23
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90095-1781
      • Jonsson Comprehensive Cancer Center, UCLA
    • Rancho Cucamonga, California, United States, 91730
      • Wilshire Oncology Medical Group, Inc.

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

Inclusion Criteria:

• 18 years of age or older
• ECOG 0-2
• Life expectancy of at least 12 weeks
• Pathologically confirmed diagnosis of metastatic colorectal cancer
• Measureable disease
• Have not received therapy for cancer within 4 weeks of enrollment on study
• Prior radiation therapy to the pelvis for treatment of colorectal cancer is allowed. Radiation therapy delivered elsewhere is allowed as long as the patient has been off treatment for at least six weeks and measurable lesions are present outside the radiation field
• Pretreatment granulocyte count of > 1500/mm3, hemoglobin > 9.0 g/dL (without transfusion), and platelet count of > 100,000/um
• Serum creatinine < 2.0 mg/dL
• Adequate hepatic function as documented by a serum bilirubin < 2.0 mg/dL regardless of whether patients have liver involvement secondary to tumor. AST must be < 3x the upper limit of normal unless the liver is involved with tumor, in which case the AST must be < 5x institutional upper limit of normal

Exclusion Criteria:

• Prior therapy with Irinotecan
• Patients with any active or uncontrolled infection
• Patients with psychiatric disorders that would interfere with consent or follow-up
• Patients with a history of myocardial infarction within the previous six months, congestive heart failure, or cerebrovascular disease
• History of prior malignancy except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer for which the patient has been disease-free for at least five years
• Presence of clinically apparent central nervous system metastases or carcinomatous meningitis
• Patients with uncontrolled diabetes mellitus
• Any other sever concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study
• Patients unable to stop taking antihypertensive medication 24 hour prior to administration of Ethyol (off x 1 day)

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: Ethyol plus Irinotecan; Ethyol 740 mg/m2 will be administered intravenously over 10 minutes. 10 minutes after completion of the Ethyol infusion, Irinotecan 250 mg/m2 will be given over 90 minutes IV.	Drug: amifostine trihydrate; Ethyol 740 mg/m2 will be administered intravenously over 10 minutes. Administered every two weeks for 3 cycles.; Other Names: Ethyol; Drug: irinotecan hydrochloride; 10 minutes after completion of the Ethyol infusion, Irinotecan 250 mg/m2 will be given over 90 minutes IV. Administered every 14 days for 3 cycles

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
To assess the toxicity profile of Irinotecan and Ethyol when administered together on this schedule.	12 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
To assess the total dose of Irinotecan received per 6 week cycle	6 weeks
To determine incidence of Irinotecan-induced leukopenia and neutropenia	12 weeks
To determine the incidence of Irinotecan-induced diarrhea	12 weeks
To determine the response rate for patients with metastatic colorectal carcinoma receiving Irinotecan and Ethyol on this dosing schedule (as measured by time response, duration of response time to progression, time of treatment failure survival).	12 weeks
To determine the clinical benefit of intravenous Irinotecan and Ethyol in patients with colorectal cancer, as measured by performance status, analgesic consumption, quality of life and survival.	12 weeks

Collaborators and Investigators

• Sponsor: Jonsson Comprehensive Cancer Center
• Collaborators: ALZA
• Investigators: Study Chair: Diane Prager, MD, Jonsson Comprehensive Cancer Center

Study record dates

Study Major Dates

• Study Start: July 1, 1997
• Primary Completion (Actual): March 1, 2000
• Study Completion (Actual): June 1, 2001

Study Registration Dates

• First Submitted: November 1, 1999
• First Submitted That Met QC Criteria: July 20, 2004
• First Posted (Estimate): July 21, 2004

Study Record Updates

• Last Update Posted (Actual): August 3, 2020
• Last Update Submitted That Met QC Criteria: July 30, 2020
• Last Verified: July 1, 2012

More Information

Terms related to this study

• Keywords: stage IV rectal cancer; stage IV colon cancer; 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; Enzyme Inhibitors; Antineoplastic Agents; Protective Agents; Topoisomerase Inhibitors; Topoisomerase I Inhibitors; Radiation-Protective Agents; Irinotecan; Amifostine
• Other Study ID Numbers: CDR0000066087; UCLA-HSPC-970304601B; ALZA-UCLA-HSPC-970304601B; NCI-G98-1390