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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00002759
First received: November 1, 1999
Last updated: February 4, 2013
Last verified: May 2006
  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. 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.


Condition Intervention Phase
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

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A PHASE I STUDY OF IRINOTECAN (CPT-11) WITH PHARMACOKINETIC MODULATION BY CYCLOSPORINE A AND PHENOBARBITAL

Resource links provided by NLM:


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

Enrollment: 3
Study Start Date: June 1996
Primary Completion Date: April 2002 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I
See detailed description.
Drug: cyclosporine Drug: irinotecan hydrochloride Drug: phenobarbital

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.

  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
  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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
Investigators
Study Chair: Mark J. Ratain, MD University of Chicago
  More Information

Additional Information:
No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00002759     History of Changes
Other Study ID Numbers: NCI-2012-02242, UCCRC-8033, NCI-T95-0100H, CDR0000064707
Study First Received: November 1, 1999
Last Updated: February 4, 2013
Health Authority: United States: Food and Drug Administration

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

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Non-Hodgkin
Neutropenia
Lymphoma, Large-Cell, Immunoblastic
Duodenal Neoplasms
Ileal Neoplasms
Jejunal Neoplasms
Intestinal Neoplasms
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
Duodenal Diseases
Intestinal Diseases
Ileal Diseases
Jejunal Diseases
Cyclosporins
Cyclosporine
Irinotecan

ClinicalTrials.gov processed this record on September 14, 2014