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Irinotecan Plus Cyclosporine and Phenobarbital in Treating Patients With Solid Tumors or Lymphoma
This study has been completed.
Sponsors and Collaborators: University of Chicago
National Cancer Institute (NCI)
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00002759
  Purpose

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
Cancer-Related Problem/Condition
Lymphoma
Small Intestine Cancer
Unspecified Adult Solid Tumor, Protocol Specific
Drug: cyclosporine
Drug: irinotecan hydrochloride
Drug: phenobarbital
Phase I

MedlinePlus related topics: Cancer Fungal Infections Hodgkin's Disease Intestinal Cancer Leukemia, Adult Acute Leukemia, Adult Chronic Lymphoma
Drug Information available for: Irinotecan Irinotecan hydrochloride Cyclosporin Cyclosporine Phenobarbital Phenobarbital sodium
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment
Official Title: A PHASE I STUDY OF IRINOTECAN (CPT-11) WITH PHARMACOKINETIC MODULATION BY CYCLOSPORINE A AND PHENOBARBITAL

Further study details as provided by National Cancer Institute (NCI):

Study Start Date: June 1996
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.

PROJECTED ACCRUAL: At least 3 patients/dose will be accrued for this study.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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 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

  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00002759

Locations
United States, Illinois
University of Chicago Cancer Research Center
Chicago, Illinois, United States, 60637-1470
Sponsors and Collaborators
University of Chicago
Investigators
Study Chair: Mark J. Ratain, MD University of Chicago
  More Information

Clinical trial summary from the National Cancer Institute's PDQ® database  This link exits the ClinicalTrials.gov site

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

Keywords provided by National Cancer Institute (NCI):
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

Study placed in the following topic categories:
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

Additional relevant MeSH terms:
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

ClinicalTrials.gov processed this record on January 14, 2009