R-(-)-Gossypol and Androgen Ablation Therapy in Treating Patients With Newly Diagnosed Metastatic Prostate Cancer

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00666666
First received: April 24, 2008
Last updated: December 12, 2012
Last verified: December 2012
  Purpose

This phase II trial is studying how well giving gossypol together with androgen ablation therapy works in treating patients with newly diagnosed metastatic prostate cancer. Gossypol may stop the growth of tumor cells by blocking blood flow to the tumor. Androgens can cause the growth of prostate tumor cells. Luteinizing hormone-releasing hormone agonists and drugs, such as bicalutamide, may lessen the amount of androgens made by the body. Giving gossypol together with androgen ablation therapy may be an effective treatment for prostate cancer


Condition Intervention Phase
Adenocarcinoma of the Prostate
Stage IV Prostate Cancer
Drug: R-(-)-gossypol acetic acid
Drug: bicalutamide
Other: laboratory biomarker analysis
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study of AT101, to Abrogate BCL-2 Mediated Resistance to Androgen Ablation Therapy in Patients With Newly Diagnosed Stage D2 Prostate Cancer

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Percentage of patients with undetectable prostate-specific antigen (PSA) (< 0.2 ng/mL) [ Time Frame: At 7 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Safety of combining AT101 and androgen ablation therapy [ Time Frame: Up to 2 years ] [ Designated as safety issue: Yes ]
  • Percentage of patients with PSA ≥ 4.0 ng/mL, overall PSA < 4.0 ng/mL, and a PSA ≥ 0.2 ng/mL but < 4.0 ng/mL [ Time Frame: Up to 7 months ] [ Designated as safety issue: No ]
  • Changes in Bcl-2 and Bax/Bak protein expression in peripheral blood mononuclear cells after treatment [ Time Frame: From baseline to 8 months ] [ Designated as safety issue: No ]
  • Bcl-2 family protein expression in baseline tumor tissue [ Time Frame: At baseline ] [ Designated as safety issue: No ]

Enrollment: 55
Study Start Date: July 2009
Primary Completion Date: May 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (R-(-)-gossypol
Patients receive R-(-)-gossypol PO QD on days 1-21. Treatment repeats every 28 weeks for 8 courses in the absence of disease progression or unacceptable toxicity. Patients may receive bicalutamide PO QD beginning 6 weeks before the initiation of R-(-)-gossypol and continuing after completion of treatment, at the discretion of the treating physician.
Drug: R-(-)-gossypol acetic acid
Given PO
Other Name: AT-101
Drug: bicalutamide
Given PO
Other Names:
  • Casodex
  • CDX
Other: laboratory biomarker analysis
Correlative studies

Detailed Description:

PRIMARY OBJECTIVE:

I. To determine the percentage of patients with newly diagnosed metastatic prostate cancer who demonstrate undetectable prostate-specific antigen (PSA) (< 0.2 ng/mL) at 7 months when treated with R-(-)-gossypol (AT-101) and androgen ablation therapy.

SECONDARY OBJECTIVES:

I. To determine the safety of this regimen in these patients. II. To determine the percentage of patients with PSA >= 4.0 ng/mL, overall PSA < 4.0 ng/mL, and a PSA >= 0.2 ng/mL but < 4.0 ng/mL during the first 7 months of therapy.

III. To determine changes in Bcl-2 and Bax/Bak protein expression in peripheral blood mononuclear cells after treatment.

IV. To analyze Bcl-2 family protein expression in baseline tumor tissue.

OUTLINE:

Patients receive R-(-)-gossypol orally (PO) once daily (QD) on days 1-21. Treatment repeats every 28 weeks for 8 courses in the absence of disease progression or unacceptable toxicity. Patients may receive bicalutamide PO QD beginning 6 weeks before the initiation of R-(-)-gossypol and continuing after completion of treatment, at the discretion of the treating physician.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Criteria:

  • Newly diagnosed disease
  • Baseline prostate-specific antigen (PSA) >= 5.0 ng/mL (within 12 weeks prior to registration)
  • No acute spinal cord compression
  • No known brain metastases
  • ECOG performance status (PS) 0-2 OR Karnofsky PS 60-100%
  • Life expectancy > 6 months
  • Total bilirubin normal
  • AST and/or ALT =< 2.5 times upper limit of normal
  • Creatinine normal OR creatinine clearance >= 60 mL/min
  • Fertile patients must use effective contraception
  • No history of allergic reactions attributed to compounds of similar chemical or biologic composition to AT-101 or other agents used in the study
  • No history of bowel obstruction or gastrointestinal (GI) motility disorder
  • No concurrent uncontrolled illness
  • No unstable angina pectoris
  • No ongoing or active infection
  • No symptomatic congestive heart failure
  • No cardiac arrhythmia
  • No psychiatric illness or social situation that would limit compliance with study requirements
  • No condition (e.g., GI tract disease resulting in an inability to take oral medication or a requirement for IV alimentation or active peptic ulcer disease) that impairs the ability to swallow and retain AT-101 tablets
  • Leukocytes >= 3,000/mcL Absolute neutrophil count >= 1,500/mcL (without transfusion)
  • At least 12 months since prior androgen ablation therapy or antiandrogen therapy in the adjuvant or neoadjuvant setting
  • No prior androgen ablation therapy for metastatic disease (beyond the 6-week induction period prior to initiation of R-(-)-gossypol [AT-101])
  • More than 4 weeks since prior radiotherapy and recovered
  • No concurrent chemotherapy or radiotherapy
  • No other concurrent investigational agents
  • No concurrent routine use of hematopoietic growth factors (including filgrastim [G-CSF], sargramostim [GM-CSF], or interleukin-11) during the first course of study treatment
  • No concurrent combination antiretroviral therapy for HIV-positive patients
  • Platelet count >= 100,000/mcL (without transfusion)
  • Histologically confirmed adenocarcinoma of the prostate
  • Clinical stage D2 disease, defined by soft tissue or bony metastasis
  • No prior surgical procedures affecting absorption
  • No prior bilateral orchiectomy
  • Other prior local surgery allowed
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00666666

Locations
United States, New Jersey
Cancer Institute of New Jersey
New Brunswick, New Jersey, United States, 08903
United States, Wisconsin
University of Wisconsin Hospital and Clinics
Madison, Wisconsin, United States, 53792
Sponsors and Collaborators
Investigators
Principal Investigator: Robert DiPaola Rutgers Cancer Institute of New Jersey
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00666666     History of Changes
Other Study ID Numbers: NCI-2009-00264, 8014, N01CM62201, U01CA062491, U01CA132194
Study First Received: April 24, 2008
Last Updated: December 12, 2012
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Adenocarcinoma
Prostatic Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Genital Diseases, Male
Prostatic Diseases
Retinol acetate
Gossypol acetic acid
Bicalutamide
Androgens
Gossypol
Adjuvants, Immunologic
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Anticarcinogenic Agents
Protective Agents
Antineoplastic Agents
Therapeutic Uses
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Contraceptive Agents, Male
Contraceptive Agents
Reproductive Control Agents
Antineoplastic Agents, Phytogenic

ClinicalTrials.gov processed this record on April 22, 2014