Study of Individualized Amonafide to Treat Prostate Cancer
The purpose of this study is to assess the safety and efficacy of Amonafide in men with androgen-independent prostate cancer, assigned to individualized doses of Amonafide based on acetylator phenotype information (doses adjusted on individual metabolism).
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Dose-Defining Study of a NAT2 Phenotype-Based Dosing Regimen of Intravenous Amonafide L-Malate Administered Weekly in Men With Androgen-Independent Prostate Cancer (AIPC)|
- The Primary Objectives of this study are:
- To define and validate the safety of a NAT2 pheontypically driven dosing regimen;
- To define the pharmacokinetic and pharmacodynamic profile of Amonafide with a weekly intravenous administration schedule.
- The Secondary Objectives of this study are:
- To determine the efficacy of weekly intravenous Amonafide for all enrolled subjects as defined by PSA response (decrease in PSA of 50% or greater), duration of PSA response, and time to PSA progression;
- To determine the overall tumor response (e.g., complete response or partial response), duration of tumor response, and time to tumor progression among subjects with measurable lesions using standard (RECIST) criteria.
|Study Start Date:||March 2004|
|Study Completion Date:||December 2005|
|Primary Completion Date:||December 2005 (Final data collection date for primary outcome measure)|
This is an open-label, Phase I/II, multicenter study of Amonafide in subjects with androgen-independent metastatic prostate cancer.
Amonafide is metabolized by N-acetylation to an active metabolite, N-acetyl-Amonafide. Inter-subject differences in N-acetylation can explain the variability in Amonafide-induced myelosuppression. This dose-defining protocol has been designed to assess safety and efficacy of Amonafide in men with androgen-independent prostate cancer, assigned to individualized doses based on acetylator phenotype information.
The total duration of this study will be approximately 12 - 16 months: approximately 6 - 10 months for enrollment, and approximately 6 months for subject screening, treatment, and follow up per protocol. Subjects will be treated until PSA progression, disease progression, or unacceptable toxicity.
Subjects may continue participation in the study after Cycle 5 at the investigator's discretion if PSA progression, disease progression, or unacceptable toxicities are not reported. If a subject fulfills a criterion of PSA progression or disease progression, yet in the opinion of the investigator, the subject appears to be deriving clinical benefit from the study medication, a request may be made to the Xanthus medical monitor to allow that subject to continue study participation on a compassionate basis.
A follow-up evaluation for all subjects will be done 30 - 35 days after receiving the last dose of Amonafide. Subjects will be contacted every 3 months for survival after completion of the active phase of the study, until death.
PSA response will be reported for all subjects receiving Amonafide treatment. PSA levels will be measured at Screening and once per treatment cycle thereafter (at Day 1 of each cycle). A PSA responder will be defined as a subject experiencing a 50% decrease in PSA level, confirmed four or more weeks later, with no demonstration of clinical or radiographic evidence of disease progression prior to the second PSA measurement. Duration PSA response and time to PSA progression will also be reported.
In addition to PSA endpoints, traditional response criteria such as overall tumor response rate (complete + partial tumor response), duration of tumor response, and time to tumor progression will be captured for all subjects with measurable lesions. All complete and partial responses must be confirmed by repeat assessments that should be performed no less than 4 weeks after the criteria for response are met.
Subsequently, in order to evaluate safety, all subjects will be assessed for signs of adverse events according to the Common Terminology Criteria for Adverse Events (CTCAE) version 3 dated June 10, 2003.
All serious adverse events (SAEs) and grade ¾ toxicities will be reviewed by the Sponsor's medical monitor. Appropriate action may be taken to terminate or put the study on hold if warranted by unanticipated toxicity.
|United States, California|
|USC Norris Comprehensive Cancer Center|
|Los Angeles, California, United States, 90033|
|United States, Maryland|
|Cancer Center at John Hopkins|
|Baltimore, Maryland, United States, 21231|
|United States, Missouri|
|Barnard Cancer Center|
|St.Louis, Missouri, United States, 63110|
|United States, New Jersey|
|Cancer Institute of New Jersey|
|New Brunswick, New Jersey, United States, 08901|
|United States, New York|
|Herbert Irving Cancer Center|
|New York, New York, United States, 10032-3789|
|United States, Ohio|
|The Cleveland Clinic|
|Cleveland, Ohio, United States, 44195|
|United States, Pennsylvania|
|Fox Chase Cancer Center|
|Philadelphia, Pennsylvania, United States, 19111-2497|
|United States, Washington|
|Seattle Cancer Care Alliance|
|Seattle, Washington, United States, 98109|
|Study Chair:||Michel Drouin, MD||Xanthus Life Sciences-Medical Monitor|
|Study Director:||Monique Champagne, BPharm, MSc||Xanthus Pharmaceuticals, Inc.|
|Principal Investigator:||Mario Eisenberger, MD||Johns Hopkins University Hospital|