Know Cancer

forgot password

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)

Phase 1/Phase 2
18 Years
Not Enrolling
Prostate Cancer

Thank you

Trial Information

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)

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.

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

- 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

- 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

- Any other known condition, which in the investigator's opinion would not make the
subject a good candidate for the trial.

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

The Primary Objectives of this study are:

Principal Investigator

Michel Drouin, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Xanthus Life Sciences-Medical Monitor


United States: Food and Drug Administration

Study ID:




Start Date:

March 2004

Completion Date:

December 2005

Related Keywords:

  • Prostate Cancer
  • Prostatic Neoplasms



Fox Chase Cancer Center Philadelphia, Pennsylvania  19111
Cancer Institute of New Jersey New Brunswick, New Jersey  08901
Seattle Cancer Care Alliance Seattle, Washington  98109
USC Norris Comprehensive Cancer Center Los Angeles, California  90089
The Cleveland Clinic Cleveland, Ohio  44195
Cancer Center at John Hopkins Baltimore, Maryland  21231
Barnard Cancer Center St.Louis, Missouri  63110
Herbert Irving Cancer Center New York, New York  10032-3789