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

A Phase I Study of DX-8951f (Exatecan Mesylate for Injection) in Patients With Renal Dysfunction

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.

Study Overview

• Status: Completed
• Conditions: Unspecified Adult Solid Tumor, Protocol Specific
• Intervention / Treatment: Drug: exatecan mesylate

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.

• Study Type: Interventional
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90095
      • Jonsson Comprehensive Cancer Center, UCLA
  • Texas
    • Fort Sam Houston, Texas, United States, 78234
      • Brooke Army Medical Center
    • San Antonio, Texas, United States, 78284
      • Veterans Affairs Medical Center - San Antonio (Murphy)
    • San Antonio, Texas, United States, 78229
      • Cancer Therapy and Research Center
    • San Antonio, Texas, United States, 78229
      • St. Luke's Lutheran Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment

Collaborators and Investigators

• Sponsor: Jonsson Comprehensive Cancer Center
• Collaborators: National Cancer Institute (NCI)
• Investigators: Study Chair: Carolyn Britten, MD, Jonsson Comprehensive Cancer Center

Study record dates

Study Major Dates

• Study Start: May 1, 2002
• Study Completion (Actual): October 1, 2007

Study Registration Dates

• First Submitted: September 6, 2002
• First Submitted That Met QC Criteria: January 26, 2003
• First Posted (Estimate): January 27, 2003

Study Record Updates

• Last Update Posted (Estimate): July 10, 2013
• Last Update Submitted That Met QC Criteria: July 9, 2013
• Last Verified: April 1, 2003

More Information

Terms related to this study

• Keywords: unspecified adult solid tumor, protocol specific
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase Inhibitors; Topoisomerase I Inhibitors; Exatecan
• Other Study ID Numbers: DAIICHI-8951A-PRT026; UCLA-0201008; CDR0000256866 (Registry Identifier: PDQ (Physician Data Query)); NCI-G02-2103