Irinotecan Plus Cyclosporine and Phenobarbital in Treating Patients With Solid Tumors or Lymphoma
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ClinicalTrials.gov Identifier: NCT00002759 |
Recruitment Status :
Completed
First Posted : March 26, 2004
Last Update Posted : February 5, 2013
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Condition or disease | Intervention/treatment | Phase |
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Drug/Agent Toxicity by Tissue/Organ Lymphoma Neutropenia Small Intestine Cancer Unspecified Adult Solid Tumor, Protocol Specific | Drug: cyclosporine Drug: irinotecan hydrochloride Drug: phenobarbital | Phase 1 |
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 (Clinical Trial) |
Actual Enrollment : | 3 participants |
Allocation: | N/A |
Intervention Model: | Single Group Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
Official Title: | A PHASE I STUDY OF IRINOTECAN (CPT-11) WITH PHARMACOKINETIC MODULATION BY CYCLOSPORINE A AND PHENOBARBITAL |
Study Start Date : | June 1996 |
Actual Primary Completion Date : | April 2002 |

Arm | Intervention/treatment |
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Experimental: Arm I
See detailed description.
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Drug: cyclosporine Drug: irinotecan hydrochloride Drug: phenobarbital |

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Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
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

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00002759
United States, Illinois | |
University of Chicago Cancer Research Center | |
Chicago, Illinois, United States, 60637-1470 |
Study Chair: | Mark J. Ratain, MD | University of Chicago |
Responsible Party: | National Cancer Institute (NCI) |
ClinicalTrials.gov Identifier: | NCT00002759 |
Other Study ID Numbers: |
NCI-2012-02242 UCCRC-8033 NCI-T95-0100H CDR0000064707 ( Registry Identifier: PDQ (Physician Data Query) ) |
First Posted: | March 26, 2004 Key Record Dates |
Last Update Posted: | February 5, 2013 |
Last Verified: | May 2006 |
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 |
Lymphoma Intestinal Neoplasms Neutropenia Drug-Related Side Effects and Adverse Reactions Neoplasms by Histologic Type Neoplasms Lymphoproliferative Disorders Lymphatic Diseases Immunoproliferative Disorders Immune System Diseases Agranulocytosis Leukopenia Leukocyte Disorders Hematologic Diseases Gastrointestinal Neoplasms |
Digestive System Neoplasms Neoplasms by Site Digestive System Diseases Gastrointestinal Diseases Intestinal Diseases Chemically-Induced Disorders Cyclosporine Irinotecan Phenobarbital Cyclosporins Topoisomerase I Inhibitors Topoisomerase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Antineoplastic Agents |