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Sponsors and Collaborators: |
University of Chicago National Cancer Institute (NCI) |
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Information provided by: | National Cancer Institute (NCI) |
ClinicalTrials.gov Identifier: | NCT00002759 |
RATIONALE: 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.
PURPOSE: 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.
Condition | Intervention | Phase |
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Cancer-Related Problem/Condition Lymphoma Small Intestine Cancer Unspecified Adult Solid Tumor, Protocol Specific |
Drug: cyclosporine Drug: irinotecan hydrochloride Drug: phenobarbital |
Phase I |
Study Type: | Interventional |
Study Design: | Treatment |
Official Title: | A PHASE I STUDY OF IRINOTECAN (CPT-11) WITH PHARMACOKINETIC MODULATION BY CYCLOSPORINE A AND PHENOBARBITAL |
Study Start Date: | June 1996 |
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.
PROJECTED ACCRUAL: At least 3 patients/dose will be accrued for this study.
Ages Eligible for Study: | 18 Years and older |
Genders Eligible for Study: | Both |
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 Hematopoietic: 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 Hepatic: Bilirubin no greater than 1.5 mg/dL AST/ALT less than twice normal (unless due to disease) PT and PTT normal Renal: Creatinine no greater than 1.5 mg/dL Creatinine clearance at least 60 mL/min Cardiovascular: No history of congestive heart failure requiring medical therapy No clinically significant or life threatening cardiac arrhythmia Pulmonary: No history of significant pulmonary disease or lymphangitic lung disease Other: 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: Biologic therapy: At least 4 weeks since prior biologic therapy At least 2 weeks since prior colony stimulating factors Chemotherapy: At least 4 weeks since prior chemotherapy (at least 6 weeks since nitrosoureas or mitomycin) No prior bleomycin or irinotecan Endocrine therapy: Not specified Radiotherapy: At least 4 weeks since prior radiotherapy to greater than 25% of bone marrow Surgery: Not specified Other: 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
United States, Illinois | |
University of Chicago Cancer Research Center | |
Chicago, Illinois, United States, 60637-1470 |
Study Chair: | Mark J. Ratain, MD | University of Chicago |
Study ID Numbers: | CDR0000064707, UCCRC-8033, NCI-T95-0100H |
Study First Received: | November 1, 1999 |
Last Updated: | October 18, 2008 |
ClinicalTrials.gov Identifier: | NCT00002759 |
Health Authority: | United States: Federal Government |
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 |
Sezary syndrome Cyclosporine Miconazole Lymphoma, Mantle-Cell Hodgkin lymphoma, adult Lymphoma, small cleaved-cell, diffuse Cyclosporins Ileal Diseases Lymphoma, large-cell, immunoblastic Central nervous system lymphoma, primary Duodenal Neoplasms Mycoses Leukemia, Lymphocytic, Chronic, B-Cell Lymphoma, Large-Cell, Anaplastic Hodgkin Disease |
Chronic lymphocytic leukemia Lymphoma, Large B-Cell, Diffuse Immunoproliferative Disorders Digestive System Neoplasms Leukemia, B-cell, chronic Camptothecin Neutropenia B-cell lymphomas Leukemia, T-Cell Gastrointestinal Neoplasms Anaplastic large cell lymphoma Lymphoma, Non-Hodgkin Lymphoma, T-Cell, Cutaneous Phenobarbital Hodgkin's disease |
Anti-Infective Agents Neurotransmitter Agents Immunologic Factors Molecular Mechanisms of Pharmacological Action Antineoplastic Agents GABA Modulators Physiological Effects of Drugs Excitatory Amino Acid Agents Neoplasms by Site Jejunal Diseases Antifungal Agents Therapeutic Uses Hypnotics and Sedatives Dermatologic Agents |
Excitatory Amino Acid Antagonists Neoplasms by Histologic Type Immune System Diseases Central Nervous System Depressants Enzyme Inhibitors Immunosuppressive Agents Pharmacologic Actions Neoplasms GABA Agents Antirheumatic Agents Antineoplastic Agents, Phytogenic Central Nervous System Agents Anticonvulsants |