Exatecan Mesylate in Treating Patients With Advanced Solid Tumors and Kidney Dysfunction

This study has been completed.
Sponsor:
Collaborator:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00045318
First received: September 6, 2002
Last updated: July 9, 2013
Last verified: April 2003
  Purpose

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die.

PURPOSE: Phase I trial to study the effectiveness of exatecan mesylate in treating patients who have advanced solid tumors and kidney dysfunction.


Condition Intervention Phase
Unspecified Adult Solid Tumor, Protocol Specific
Drug: exatecan mesylate
Phase 1

Study Type: Interventional
Study Design: Primary Purpose: Treatment
Official Title: A Phase I Study of DX-8951f (Exatecan Mesylate for Injection) in Patients With Renal Dysfunction

Resource links provided by NLM:


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

Study Start Date: May 2002
Study Completion Date: October 2007
Detailed Description:

OBJECTIVES:

  • Determine the maximum tolerated dose of exatecan mesylate in patients with advanced solid tumors and varying degrees of renal dysfunction.
  • Determine the dose-limiting and non-dose-limiting toxic effects of this drug in these patients.
  • Determine the effects of renal dysfunction on the plasma pharmacokinetics and pharmacodynamics of this drug in these patients.
  • Establish a model for dosing this drug in patients with impaired renal function.

OUTLINE: This is a dose-escalation, multicenter study. Patients are stratified according to severity of renal dysfunction (normal vs mild vs moderate vs severe).

Patients receive exatecan mesylate IV over 30 minutes on days 1-5. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients in each renal dysfunction stratum receive escalating doses of exatecan mesylate until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Patients in the normal renal function stratum do not undergo dose escalation.

Patients are followed every 3 months.

PROJECTED ACCRUAL: A total of 45 patients (6 normal, 9 mild, 12 moderate, and 18 severe renal dysfunction) will be accrued for this study within 1.5 years.

  Eligibility

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

DISEASE CHARACTERISTICS:

  • Histologically or cytologically confirmed advanced solid tumor refractory to standard therapy or for which no standard therapy exists
  • Renal function as defined by the following parameters:

    • Normal (creatinine clearance (CrCl) greater than 80 mL/min)
    • Mild dysfunction (CrCl 50-80 mL/min)
    • Moderate dysfunction (CrCl 30-50 mL/min)
    • Severe dysfunction (CrCl less than 30 mL/min)
    • End-stage renal disease (requiring dialysis)
  • No symptomatic or active brain metastases (e.g., edema or progression on CT scan or MRI)

PATIENT CHARACTERISTICS:

Age

  • 18 and over

Performance status

  • ECOG 0-2

Life expectancy

  • At least 12 weeks

Hematopoietic

  • Absolute neutrophil count at least 1,500/mm3
  • Platelet count at least 100,000/mm3
  • Hemoglobin at least 9.0 g/dL

Hepatic

  • Bilirubin normal
  • AST or ALT no greater than 2 times upper limit of normal
  • Albumin at least 2.8 g/dL

Renal

  • See Disease Characteristics

Cardiovascular

  • No active congestive heart failure
  • No uncontrolled angina
  • No myocardial infarction within the past 6 months

Other

  • No concurrent serious infection
  • No other life-threatening illness
  • No overt psychosis or mental disability or other incompetency that would preclude informed consent
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • No concurrent anticancer biologic therapy

Chemotherapy

  • At least 4 weeks since prior chemotherapy (6 weeks for mitomycin or nitrosourea) and recovered
  • No prior exatecan mesylate
  • No other concurrent anticancer chemotherapy

Endocrine therapy

  • No concurrent anticancer hormonal therapy
  • Concurrent megestrol for appetite stimulation allowed

Radiotherapy

  • At least 4 weeks since prior radiotherapy and recovered
  • No concurrent anticancer radiotherapy

Surgery

  • At least 4 weeks since prior major surgery and recovered
  • No concurrent anticancer surgery

Other

  • At least 4 weeks since prior investigational drugs including analgesics or antiemetics
  • At least 1 week since prior grapefruit juice
  • No other concurrent anticancer therapy
  • No other investigational drugs during and for 4 weeks after study
  • No concurrent grapefruit juice
  • No other concurrent anticancer cytotoxic therapy
  • Concurrent chronic hemodialysis or ambulatory peritoneal dialysis allowed
  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: NCT00045318

Locations
United States, California
Jonsson Comprehensive Cancer Center, UCLA
Los Angeles, California, United States, 90095
United States, Texas
Brooke Army Medical Center
Fort Sam Houston, Texas, United States, 78234
Cancer Therapy and Research Center
San Antonio, Texas, United States, 78229
St. Luke's Lutheran Hospital
San Antonio, Texas, United States, 78229
Veterans Affairs Medical Center - San Antonio (Murphy)
San Antonio, Texas, United States, 78284
Sponsors and Collaborators
Jonsson Comprehensive Cancer Center
Investigators
Study Chair: Carolyn Britten, MD Jonsson Comprehensive Cancer Center
  More Information

Additional Information:
No publications provided

ClinicalTrials.gov Identifier: NCT00045318     History of Changes
Other Study ID Numbers: DAIICHI-8951A-PRT026, UCLA-0201008, CDR0000256866, NCI-G02-2103
Study First Received: September 6, 2002
Last Updated: July 9, 2013
Health Authority: United States: Federal Government

Keywords provided by National Cancer Institute (NCI):
unspecified adult solid tumor, protocol specific

Additional relevant MeSH terms:
Exatecan
Camptothecin
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antineoplastic Agents, Phytogenic

ClinicalTrials.gov processed this record on August 28, 2014