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


Phase 1
18 Years
N/A
Not Enrolling
Both
Unspecified Adult Solid Tumor, Protocol Specific

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Trial Information

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


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.

Inclusion 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

Type of Study:

Interventional

Study Design:

Primary Purpose: Treatment

Principal Investigator

Carolyn Britten, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Jonsson Comprehensive Cancer Center

Authority:

United States: Federal Government

Study ID:

DAIICHI-8951A-PRT026

NCT ID:

NCT00045318

Start Date:

May 2002

Completion Date:

October 2007

Related Keywords:

  • Unspecified Adult Solid Tumor, Protocol Specific
  • unspecified adult solid tumor, protocol specific

Name

Location

Jonsson Comprehensive Cancer Center, UCLALos Angeles, California  90095-1781
Brooke Army Medical CenterFort Sam Houston, Texas  78234-6200
Veterans Affairs Medical Center - San Antonio (Murphy)San Antonio, Texas  78284
Cancer Therapy and Research CenterSan Antonio, Texas  78229
St. Luke's Lutheran HospitalSan Antonio, Texas  78229