A Phase I Study of DX-8951f (Exatecan Mesylate for Injection) in Patients With Renal Dysfunction
Exatecan Mesylate in Treating Patients With Advanced Solid Tumors and Kidney Dysfunction
Sponsors
Source
National Cancer Institute (NCI)
Brief Summary
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.
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.
Overall Status
Completed
Start Date
2002-05-01
Completion Date
2007-10-01
Primary Completion Date
N/A
Phase
Phase 1
Study Type
Interventional
Condition
Intervention
Eligibility
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
Gender
All
Minimum Age
18 Years
Maximum Age
N/A
Healthy Volunteers
No
Overall Official
Last Name |
Role |
Affiliation |
|
Carolyn Britten, MD |
Study Chair |
Jonsson Comprehensive Cancer Center |
Location
Facility |
|
Jonsson Comprehensive Cancer Center, UCLA Los Angeles California 90095 United States |
|
Brooke Army Medical Center Fort Sam Houston Texas 78234 United States |
|
Cancer Therapy and Research Center San Antonio Texas 78229 United States |
|
St. Luke's Lutheran Hospital San Antonio Texas 78229 United States |
|
Veterans Affairs Medical Center - San Antonio (Murphy) San Antonio Texas 78284 United States |
Location Countries
Country
United States
Verification Date
2003-04-01
Lastchanged Date
N/A
Firstreceived Date
N/A
Keyword
Has Expanded Access
No
Secondary Id
UCLA-0201008
CDR0000256866
NCI-G02-2103
Intervention Browse
Mesh Term
Exatecan
Camptothecin
Firstreceived Results Date
N/A
Firstreceived Results Disposition Date
N/A
Study Design Info
Primary Purpose
Treatment
Study First Submitted
September 6, 2002
Study First Submitted Qc
January 26, 2003
Study First Posted
January 27, 2003
Last Update Submitted
July 9, 2013
Last Update Submitted Qc
July 9, 2013
Last Update Posted
July 10, 2013
ClinicalTrials.gov processed this data on December 10, 2019
Conditions
Conditions usually refer to a disease, disorder, syndrome, illness, or injury. In ClinicalTrials.gov,
conditions include any health issue worth studying, such as lifespan, quality of life, health risks, etc.
Interventions
Interventions refer to the drug, vaccine, procedure, device, or other potential treatment being studied.
Interventions can also include less intrusive possibilities such as surveys, education, and interviews.
Study Phase
Most clinical trials are designated as phase 1, 2, 3, or 4, based on the type of questions
that study is seeking to answer:
In Phase 1 (Phase I) clinical trials, researchers test a new drug or treatment in a small group of people (20-80) for the first time to evaluate its safety, determine a safe dosage range, and identify side effects.
In Phase 2 (Phase II) clinical trials, the study drug or treatment is given to a larger group of people (100-300) to see if it is effective and to further evaluate its safety.
In Phase 3 (Phase III) clinical trials, the study drug or treatment is given to large groups of people (1,000-3,000) to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely.
In Phase 4 (Phase IV) clinical trials, post marketing studies delineate additional information including the drug's risks, benefits, and optimal use.
These phases are defined by the Food and Drug Administration in the Code of Federal Regulations.
In Phase 1 (Phase I) clinical trials, researchers test a new drug or treatment in a small group of people (20-80) for the first time to evaluate its safety, determine a safe dosage range, and identify side effects.
In Phase 2 (Phase II) clinical trials, the study drug or treatment is given to a larger group of people (100-300) to see if it is effective and to further evaluate its safety.
In Phase 3 (Phase III) clinical trials, the study drug or treatment is given to large groups of people (1,000-3,000) to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely.
In Phase 4 (Phase IV) clinical trials, post marketing studies delineate additional information including the drug's risks, benefits, and optimal use.
These phases are defined by the Food and Drug Administration in the Code of Federal Regulations.