Study of AS1404 With Docetaxel in Patients With Hormone Refractory Metastatic 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: NCT00111618
Recruitment Status : Completed
First Posted : May 25, 2005
Last Update Posted : January 30, 2009
Information provided by:
Antisoma Research

Brief Summary:
The purpose of this trial is to confirm a safe dose of AS1404, to be given with docetaxel, and to see whether adding AS1404 and docetaxel together improves the outcome of the treatment, when compared to docetaxel alone.

Condition or disease Intervention/treatment Phase
Prostate Cancer Drug: AS1404 (DMXAA) Phase 2

Detailed Description:
The overall aim of this study is to determine the safety, tolerability and efficacy of AS1404 in combination with docetaxel in patients with hormone refractory metastatic prostate cancer.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 70 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open Label, Randomized, Phase II Study of AS1404 in Combination With Docetaxel in Patients With Hormone Refractory Metastatic Prostate Cancer
Study Start Date : May 2005
Actual Primary Completion Date : June 2007
Actual Study Completion Date : August 2008

Resource links provided by the National Library of Medicine

Primary Outcome Measures :
  1. Laboratory safety
  2. Adverse event monitoring
  3. Electrocardiogram (EKG)
  4. Ophthalmic assessments
  5. Tumor assessment
  6. Time to progression and survival time
  7. Prostate-specific antigen (PSA)
  8. Pharmacokinetic sampling

Information from the National Library of Medicine

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

Inclusion Criteria:

  • Age equal to, or greater than 18 years
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-2
  • Life expectancy greater than or equal to 3 months
  • Histopathologically confirmed adenocarcinoma of the prostate
  • Metastatic progressive androgen-independent prostate cancer with no previous chemotherapy treatment
  • At least 4 weeks off of flutamide and 6 weeks off of bicalutamide and nilutamide
  • Patients who have not undergone surgical castration must continue treatment with an luteinizing hormone-releasing hormone (LHRH) agonist. In those patients where, for some reason, the LHRH agonist has been discontinued prior to entry on the study, it should be reinstituted and disease progression must be documented.
  • Hematological and biochemical indices at screening within the following ranges:

    • An absolute neutrophil count of greater than or equal to 1.5 x 10^9/L;
    • A platelet count of greater than or equal to 100 x 10^9/L;
    • A hemoglobin level of greater than or equal to 10 g/dL.
  • Adequate hepatic and renal function, as defined by:

    • Serum bilirubin less than or equal to upper limit of normal (ULN);
    • SGOT and/or SGPT less than or equal to 1.5 x ULN concomitant with alkaline phosphatase less than or equal to 2.5 x ULN;
    • Serum creatinine less than or equal to 120 micromol/L or creatinine clearance greater than or equal to 60 mL/min.
  • Be willing and able to provide written informed consent and, in the opinion of the Investigator, be able to comply with the study assessments and follow-up
  • Serum testosterone no greater than 50 ng/mL (chemically castrated patients only)

Exclusion Criteria:

  • Decreasing PSA levels after antiandrogen withdrawal
  • Previous chemotherapy treatment for prostate cancer
  • Patients who have received blood transfusions or growth factors to aid hematological recovery within two weeks of scheduled baseline visit
  • Concurrent severe and/or uncontrolled co-morbid medical condition within 2 weeks of screening
  • Previous exposure to AS1404 or other vascular targeting agents
  • Clinically significant cardiac arrhythmias and known QTc prolongation (interval >450 msec)
  • Evidence of severe or uncontrolled systemic disease that, in the opinion of the Investigator, might interfere with the patient's participation in the study
  • A history of alcoholism; drug addiction; or any psychiatric condition, which, in the opinion of the Investigator, would impair the patient's ability to comply with study procedures
  • A history of hypersensitivity to taxanes or other drugs formulated with polysorbate 80
  • Treatment with the following medications within two weeks of AS1404 administration or the expected need for such treatments during the study period:

    • Medications known to modulate serotonin;
    • Medications known to affect the QT interval;
    • Current treatment with, or the expected need during the treatment period for ketoconazole, erythromycin, troleandomycin, and/or cyclosporine. The use of other agents known to induce, inhibit, or that are metabolized by cytochrome P450-3A4 should be undertaken with caution.
  • Concurrent or previous malignancy of a different tumor type within five years of starting the study, except for adequately treated non-melanoma skin cancer
  • Clinical or radiological evidence of central nervous system (CNS) metastases
  • Symptomatic peripheral neuropathy greater than or equal to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) grade II
  • Evidence of any other significant clinical disorder or laboratory finding that, in the opinion of the Investigator, compromises the patient safety during study participation
  • Participation in any prostate cancer investigational drug study in which the study drug has not subsequently obtained a product license
  • Any other concurrent treatment for prostate cancer (with the exception of palliative radiotherapy) other than that specified in the protocol, including the use of herbal remedies, (e.g. saw palmetto)

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): NCT00111618

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Sponsors and Collaborators
Antisoma Research
Principal Investigator: Roberto Pili, MD The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Publications automatically indexed to this study by Identifier (NCT Number): Identifier: NCT00111618     History of Changes
Obsolete Identifiers: NCT00119275
Other Study ID Numbers: AS1404-203
First Posted: May 25, 2005    Key Record Dates
Last Update Posted: January 30, 2009
Last Verified: January 2009

Keywords provided by Antisoma Research:
vascular disrupting agent
hormone refractory prostate cancer

Additional relevant MeSH terms:
Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Genital Diseases, Male
Prostatic Diseases
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs