Irinotecan Plus Cyclosporine and Phenobarbital in Treating Patients With Solid Tumors or Lymphoma

February 4, 2013 updated by: National Cancer Institute (NCI)

A PHASE I STUDY OF IRINOTECAN (CPT-11) WITH PHARMACOKINETIC MODULATION BY CYCLOSPORINE A AND PHENOBARBITAL

Phase I trial to study the effectiveness of irinotecan plus cyclosporine and phenobarbital in treating patients who have solid tumors or lymphoma that is refractory to standard therapy. Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Cyclosporine and phenobarbital may enhance the effectiveness of irinotecan.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

OBJECTIVES:

I. Determine the maximum tolerated dose of irinotecan (CPT-11) when infused weekly with cyclosporine (CYSP) in patients with solid tumors or lymphoma refractory to standard therapy.

II. Determine whether CYSP modulates the pharmacokinetics and pharmacodynamics of CPT-11 and its active metabolite, SN-38.

III. Determine whether phenobarbital modulates the pharmacokinetics and pharmacodynamics of CPT-11 and SN-38.

OUTLINE: This is a dose escalation study of irinotecan. Patients are stratified according to gender.

Part I: Patients receive cyclosporine IV over 6 hours and irinotecan IV over 90 minutes weekly for 4 weeks. Courses repeat every 6 weeks in the absence of unacceptable toxicity or disease progression. Cohorts of 3-12 patients receive escalating doses of irinotecan until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which at least one third of patients experience dose limiting toxicity (DLT).

Part IIA: If the DLT is diarrhea in part I, then part IIA is opened. Patients receive oral phenobarbital, cyclosporine as in part I, and irinotecan at the MTD from part I. Dose escalation occurs as in part I to determine a new MTD. If the DLT continues to be diarrhea, the study is closed. Part IIB: If the DLT is neutropenia in part I, then part IIB is opened. Patients receive cyclosporine as in part I and escalating doses of irinotecan to determine a new MTD.

Part III: If the DLT is neutropenia in part IIA or any DLT in part IIB, patients receive phenobarbital, cyclosporine, and irinotecan at the MTD determined as in part IIA or part IIB. Dose escalation continues until a new MTD is determined.

Study Type

Interventional

Enrollment (Actual)

3

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Illinois
      • Chicago, Illinois, United States, 60637-1470
        • University of Chicago Cancer Research Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

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:

  • Malignant solid tumor or lymphoma refractory to standard therapy or for which no therapy of proven benefit exists
  • No leukemia
  • Measurable or evaluable disease

PATIENT CHARACTERISTICS:

  • Age: 18 and over
  • Performance status: Karnofsky 70-100%
  • Life expectancy: At least 3 months
  • WBC at least 3,500/mm3
  • Absolute neutrophil count at least 1,500/mm3
  • Platelet count at least 100,000/mm3
  • Hemoglobin at least 9 g/dL
  • Bilirubin no greater than 1.5 mg/dL
  • AST/ALT less than twice normal (unless due to disease)
  • PT and PTT normal
  • Creatinine no greater than 1.5 mg/dL
  • Creatinine clearance at least 60 mL/min
  • No history of congestive heart failure requiring medical therapy
  • No clinically significant or life threatening cardiac arrhythmia
  • No history of significant pulmonary disease or lymphangitic lung disease
  • No hypersensitivity to cyclosporine or cremophore
  • No history of manifest or latent porphyria or hypersensitivity to barbiturates (for parts of study using phenobarbital)
  • No history of inflammatory bowel disease requiring therapy
  • No chronic diarrhea syndrome or paralytic ileus
  • No medical or psychiatric condition that precludes informed consent
  • Not pregnant
  • Effective contraception required of fertile women

PRIOR CONCURRENT THERAPY:

  • At least 4 weeks since prior biologic therapy
  • At least 2 weeks since prior colony stimulating factors
  • At least 4 weeks since prior chemotherapy (at least 6 weeks since nitrosoureas or mitomycin)
  • No prior bleomycin or irinotecan
  • At least 4 weeks since prior radiotherapy to greater than 25% of bone marrow
  • Minimum time interval between prior therapy and eligibility shortened by 2 weeks when phenobarbital is administered
  • Concurrent use of medications that affect the central nervous or cardiovascular systems (e.g., anticonvulsants, calcium channel blockers, oral contraceptives) must be approved by the Principal Investigator

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Arm I
See detailed description.
Drug: irinotecan hydrochloride
Drug: cyclosporine
Drug: phenobarbital

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Cancer Institute (NCI)

Investigators

  • Study Chair: Mark J. Ratain, MD, University of Chicago

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 1, 1996

Primary Completion (Actual)

April 1, 2002

Study Registration Dates

First Submitted

November 1, 1999

First Submitted That Met QC Criteria

March 25, 2004

First Posted (Estimate)

March 26, 2004

Study Record Updates

Last Update Posted (Estimate)

February 5, 2013

Last Update Submitted That Met QC Criteria

February 4, 2013

Last Verified

May 1, 2006

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NCI-2012-02242
  • UCCRC-8033
  • NCI-T95-0100H
  • CDR0000064707 (Registry Identifier: PDQ (Physician Data Query))

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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