Study of Individualized Amonafide to Treat Prostate Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00087854
Recruitment Status : Completed
First Posted : July 16, 2004
Last Update Posted : April 23, 2008
Information provided by:
Xanthus Pharmaceuticals, Inc.

Brief Summary:
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).

Condition or disease Intervention/treatment Phase
Prostate Cancer Drug: Amonafide L-malate (drug) Phase 1 Phase 2

Detailed Description:

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.

Study Type : Interventional  (Clinical Trial)
Enrollment : 40 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (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)
Study Start Date : March 2004
Actual Primary Completion Date : December 2005
Actual Study Completion Date : December 2005

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Prostate Cancer
Drug Information available for: Malic acid
U.S. FDA Resources

Primary Outcome Measures :
  1. The Primary Objectives of this study are:
  2. To define and validate the safety of a NAT2 pheontypically driven dosing regimen;
  3. To define the pharmacokinetic and pharmacodynamic profile of Amonafide with a weekly intravenous administration schedule.

Secondary Outcome Measures :
  1. The Secondary Objectives of this study are:
  2. 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;
  3. 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.

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Men 18 years or older;
  • Metastatic androgen-independent prostate cancer with evidence of progression;
  • Zero or one prior course of chemotherapy for metastatic disease;
  • Up to two prior courses of non-cytotoxic therapies for metastatic disease;
  • Progressive measurable or assessable disease;
  • Evidence of continued elevation of PSA despite antiandrogen withdrawal;
  • ECOG Performance Status < 2 with an expected survival of at least 6 months;
  • Adequate renal function;
  • Adequate hepatic function;
  • Adequate hematologic status;
  • No other prior malignancy is allowed except for the following: adequately-treated basal cell or squamous cell skin cancer, adequately treated Stage I or II bladder cancer from which the subject is currently in complete remission, or any other cancer from which the subject has been disease free for 5 years;
  • Subjects must have recovered from all acute toxicities from prior treatment;
  • Screening visit phenotyping procedures must have been completed successfully;
  • No blood transfusion within the previous 2 weeks of signature of the informed consent;
  • Expected cooperation of the subject for the treatment and follow up must be obtained and documented;
  • Written informed consent must be obtained and documented.

Exclusion Criteria:

  • Clinically significant abnormal hematological parameters other than those defined in the inclusion criteria;
  • Clinically significant abnormal biochemical parameters other than those defined in the inclusion criteria;
  • Subjects who have been receiving bisphosphonates for less than three months prior to the first Amonafide administration;
  • Known history of brain metastases;
  • Subjects who are HIV positive;
  • Subjects who are hepatitis B surface antigen positive or have previously documented hepatitis C infection;
  • Subjects who received treatment with Growth Factors (i.e. G-CSF, GM-CSF) within 2 weeks of the signature of the informed consent form;
  • Subjects who had any major surgery within four weeks of first administration of Amonafide;
  • Subjects with a history of a psychological illness or condition which may interfere with the subjects ability to understand or comply with the requirements of the study;
  • Subjects who received an investigational new drug within 30 days of the first dose of Amonafide;
  • Any other known condition, which in the investigator's opinion would not make the subject a good candidate for the trial.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00087854

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
Sponsors and Collaborators
Xanthus Pharmaceuticals, Inc.
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 Identifier: NCT00087854     History of Changes
Other Study ID Numbers: 0001A2-200-US
First Posted: July 16, 2004    Key Record Dates
Last Update Posted: April 23, 2008
Last Verified: April 2008

Additional relevant MeSH terms:
Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Genital Diseases, Male
Prostatic Diseases
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action