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

Primary Purpose

Drug/Agent Toxicity by Tissue/Organ, Lymphoma, Neutropenia

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
cyclosporine
irinotecan hydrochloride
phenobarbital
Sponsored by
National Cancer Institute (NCI)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Drug/Agent Toxicity by Tissue/Organ focused on measuring stage III adult Hodgkin lymphoma, stage IV adult Hodgkin lymphoma, recurrent adult Hodgkin lymphoma, stage III cutaneous T-cell non-Hodgkin lymphoma, stage IV cutaneous T-cell non-Hodgkin lymphoma, recurrent cutaneous T-cell non-Hodgkin lymphoma, small intestine lymphoma, unspecified adult solid tumor, protocol specific, stage III grade 1 follicular lymphoma, stage III grade 2 follicular lymphoma, stage III grade 3 follicular lymphoma, stage III adult diffuse small cleaved cell lymphoma, stage III adult diffuse mixed cell lymphoma, stage III adult diffuse large cell lymphoma, stage III adult immunoblastic large cell lymphoma, stage III adult lymphoblastic lymphoma, stage III adult Burkitt lymphoma, stage IV grade 1 follicular lymphoma, stage IV grade 2 follicular lymphoma, stage IV grade 3 follicular lymphoma, stage IV adult diffuse small cleaved cell lymphoma, stage IV adult diffuse mixed cell lymphoma, stage IV adult diffuse large cell lymphoma, stage IV adult immunoblastic large cell lymphoma, stage IV adult lymphoblastic lymphoma, stage IV adult Burkitt lymphoma, recurrent grade 1 follicular lymphoma, recurrent grade 2 follicular lymphoma, recurrent grade 3 follicular lymphoma, recurrent adult diffuse small cleaved cell lymphoma, recurrent adult diffuse mixed cell lymphoma, recurrent adult diffuse large cell lymphoma, recurrent adult immunoblastic large cell lymphoma, recurrent adult lymphoblastic lymphoma, recurrent adult Burkitt lymphoma, stage III adult T-cell leukemia/lymphoma, stage IV adult T-cell leukemia/lymphoma, recurrent adult T-cell leukemia/lymphoma, primary central nervous system non-Hodgkin lymphoma, drug/agent toxicity by tissue/organ, neutropenia, AIDS-related peripheral/systemic lymphoma, AIDS-related primary CNS lymphoma, intraocular lymphoma, stage III mantle cell lymphoma, stage IV mantle cell lymphoma, recurrent mantle cell lymphoma, angioimmunoblastic T-cell lymphoma, anaplastic large cell lymphoma, stage III mycosis fungoides/Sezary syndrome, stage IV mycosis fungoides/Sezary syndrome, recurrent mycosis fungoides/Sezary syndrome, recurrent marginal zone lymphoma, recurrent small lymphocytic lymphoma, stage III small lymphocytic lymphoma, stage III marginal zone lymphoma, stage IV small lymphocytic lymphoma, stage IV marginal zone lymphoma, extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue, nodal marginal zone B-cell lymphoma, splenic marginal zone lymphoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • University of Chicago Cancer Research Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Arm I

Arm Description

See detailed description.

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

First Posted
November 1, 1999
Last Updated
February 4, 2013
Sponsor
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00002759
Brief Title
Irinotecan Plus Cyclosporine and Phenobarbital in Treating Patients With Solid Tumors or Lymphoma
Official Title
A PHASE I STUDY OF IRINOTECAN (CPT-11) WITH PHARMACOKINETIC MODULATION BY CYCLOSPORINE A AND PHENOBARBITAL
Study Type
Interventional

2. Study Status

Record Verification Date
May 2006
Overall Recruitment Status
Completed
Study Start Date
June 1996 (undefined)
Primary Completion Date
April 2002 (Actual)
Study Completion Date
undefined (undefined)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Cancer Institute (NCI)

4. Oversight

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Drug/Agent Toxicity by Tissue/Organ, Lymphoma, Neutropenia, Small Intestine Cancer, Unspecified Adult Solid Tumor, Protocol Specific
Keywords
stage III adult Hodgkin lymphoma, stage IV adult Hodgkin lymphoma, recurrent adult Hodgkin lymphoma, stage III cutaneous T-cell non-Hodgkin lymphoma, stage IV cutaneous T-cell non-Hodgkin lymphoma, recurrent cutaneous T-cell non-Hodgkin lymphoma, small intestine lymphoma, unspecified adult solid tumor, protocol specific, stage III grade 1 follicular lymphoma, stage III grade 2 follicular lymphoma, stage III grade 3 follicular lymphoma, stage III adult diffuse small cleaved cell lymphoma, stage III adult diffuse mixed cell lymphoma, stage III adult diffuse large cell lymphoma, stage III adult immunoblastic large cell lymphoma, stage III adult lymphoblastic lymphoma, stage III adult Burkitt lymphoma, stage IV grade 1 follicular lymphoma, stage IV grade 2 follicular lymphoma, stage IV grade 3 follicular lymphoma, stage IV adult diffuse small cleaved cell lymphoma, stage IV adult diffuse mixed cell lymphoma, stage IV adult diffuse large cell lymphoma, stage IV adult immunoblastic large cell lymphoma, stage IV adult lymphoblastic lymphoma, stage IV adult Burkitt lymphoma, recurrent grade 1 follicular lymphoma, recurrent grade 2 follicular lymphoma, recurrent grade 3 follicular lymphoma, recurrent adult diffuse small cleaved cell lymphoma, recurrent adult diffuse mixed cell lymphoma, recurrent adult diffuse large cell lymphoma, recurrent adult immunoblastic large cell lymphoma, recurrent adult lymphoblastic lymphoma, recurrent adult Burkitt lymphoma, stage III adult T-cell leukemia/lymphoma, stage IV adult T-cell leukemia/lymphoma, recurrent adult T-cell leukemia/lymphoma, primary central nervous system non-Hodgkin lymphoma, drug/agent toxicity by tissue/organ, neutropenia, AIDS-related peripheral/systemic lymphoma, AIDS-related primary CNS lymphoma, intraocular lymphoma, stage III mantle cell lymphoma, stage IV mantle cell lymphoma, recurrent mantle cell lymphoma, angioimmunoblastic T-cell lymphoma, anaplastic large cell lymphoma, stage III mycosis fungoides/Sezary syndrome, stage IV mycosis fungoides/Sezary syndrome, recurrent mycosis fungoides/Sezary syndrome, recurrent marginal zone lymphoma, recurrent small lymphocytic lymphoma, stage III small lymphocytic lymphoma, stage III marginal zone lymphoma, stage IV small lymphocytic lymphoma, stage IV marginal zone lymphoma, extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue, nodal marginal zone B-cell lymphoma, splenic marginal zone lymphoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
3 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Arm I
Arm Type
Experimental
Arm Description
See detailed description.
Intervention Type
Drug
Intervention Name(s)
cyclosporine
Intervention Type
Drug
Intervention Name(s)
irinotecan hydrochloride
Intervention Type
Drug
Intervention Name(s)
phenobarbital

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Mark J. Ratain, MD
Organizational Affiliation
University of Chicago
Official's Role
Study Chair
Facility Information:
Facility Name
University of Chicago Cancer Research Center
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637-1470
Country
United States

12. IPD Sharing Statement

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

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