R-(-)-Gossypol and Androgen Ablation Therapy in Treating Patients With Newly Diagnosed 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: NCT00666666
Recruitment Status : Completed
First Posted : April 25, 2008
Results First Posted : December 18, 2014
Last Update Posted : December 18, 2014
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Brief Summary:
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 or disease Intervention/treatment Phase
Adenocarcinoma of the Prostate Stage IV Prostate Cancer Drug: AT-101 Drug: Bicalutamide Other: LHRH agent Phase 2

Detailed Description:


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.


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.


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.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 55 participants
Intervention Model: Single Group Assignment
Masking: None (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
Study Start Date : July 2009
Primary Completion Date : May 2011
Study Completion Date : June 2012

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Prostate Cancer
U.S. FDA Resources

Arm Intervention/treatment
Experimental: AT101 (R-(-)-gossypol acetic acid)
Patients will receive Hormone therapy with at least one LHRH agent (Leuprolide Acetate or Goserelin) for 6 weeks and include bicalutamide. Patients will begin AT101 daily at 6 weeks for 3 weeks of every 4 weeks (4 weeks - 1 cycle) and continue for 8 cycles of combined therapy (combined AT101, and LHRH agonist). After 8 cycles patients will continue hormonal therapy.
Drug: AT-101
AT101 will be administered orally 20 mg/day for 21 days of a 28 day cycle.
Other Name: R-(-)-gossypol acetic acid
Drug: Bicalutamide
Daily bicalutamide 50 mg po is encouraged for the first month of LHRH agonist therapy to prevent a flare. Continued bicalutamide use is optional. Bicalutamide will be administered orally at a dose of 50 mg po daily, Day 1 to 28 of each cycle.
Other Names:
  • Casodex
  • CDX
Other: LHRH agent
An LHRH agonist(Leuprolide Acetate or Goserelin)can be administered at standard dosing appropriate to the agent used.
Other Name: Leutinizing Hormone Receptor Hormone agonist

Primary Outcome Measures :
  1. Percentage of Patients With Undetectable Prostate-specific Antigen (PSA) (< 0.2 ng/mL) at End of 7 Cycles [ Time Frame: 3 years ]

Secondary Outcome Measures :
  1. Percentage of Patients With PSA ≥ 0.2 ng/mL But < 4.0 ng/mL [ Time Frame: 3 years ]
  2. Percentage of Patients With Overall PSA < 4.0 ng/mL [ Time Frame: 3 years ]

Information from the National Library of Medicine

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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

  • Histologically proven adenocarcinoma of the prostate with clinical stage D2 disease defined by soft tissue or bony metastasis.
  • Patients must have elevated PSA ≥ 5 ng/ml within 12 weeks prior to registration. Androgen ablation therapy, which must include an LHRH agonist, will begin 6 weeks prior to initiation of AT101.
  • Patients are allowed prior local therapy with radiation or surgery. Patients must not have received more than 12 months of androgen ablation therapy or antiandrogen therapy in the adjuvant/neoadjuvant setting and no prior androgen ablation therapy for metastatic disease, beyond the six week induction period prior to initiation of AT101. Patients with prior adjuvant/neoadjuvant androgen ablation therapy must have completed such therapy at least 12 months prior.
  • Must be 18 years old or older.
  • Life expectancy of greater than 6 months.
  • ECOG performance status ≤ 2.
  • Patients must have normal organ and marrow function as defined below:

    • leukocytes ≥ 3,000/mcL
    • absolute neutrophil count ≥ 1,500/mcL
    • platelets ≥ 100,000/mcL
    • total bilirubin within normal institutional limits
    • AST(SGOT)/ALT(SGPT) ≤ 2.5 X institutional upper limit of normal
    • creatinine within normal institutional limits OR
    • creatinine clearance ≥ 60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal
  • There must be no plans to receive concomitant chemotherapy or radiation therapy during the study period. Baseline and on study PSA values must be obtained from the same reference laboratory.
  • The effects of AT101 on the developing human fetus at the recommended therapeutic dose are unknown. For this reason men and/or their partners must agree to use adequate contraception, (including hormonal or barrier method of birth control, abstinence) prior to study entry and for the duration of study participation.

Exclusion Criteria

  • Patients who have had radiotherapy within 4 weeks prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier.
  • Patients may not be receiving any other investigational agents.
  • Patients with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to AT101 or other agents used in the study.
  • Patients with bilateral orchiectomy are not eligible.
  • Patients presenting with acute cord compression are not eligible.
  • History of bowel obstruction or GI dismotility disorder.
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
  • Any condition (e.g., gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for IV alimentation, prior surgical procedures affecting absorption, or active peptic ulcer disease) that impairs their ability to swallow and retain AT-101 tablets.
  • Requirement for routine use of hematopoietic growth factors (including granulocyte colony stimulating factor, granulocyte macrophage colony stimulating factor, or interleukin-11) or platelet transfusions to maintain absolute neutrophil counts or platelets counts above the required thresholds for study entry.
  • HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with AT-101.

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): NCT00666666

United States, Illinois
University of Chicago
Chicago, Illinois, United States, 60637
United States, Michigan
University of Michigan
Ann Arbor, Michigan, United States, 48109
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
National Cancer Institute (NCI)
Principal Investigator: Robert DiPaola Rutgers Cancer Institute of New Jersey

Responsible Party: National Cancer Institute (NCI) Identifier: NCT00666666     History of Changes
Other Study ID Numbers: NCI-2009-00264
8014 ( Other Identifier: NCI/CTEP )
N01CM62201 ( U.S. NIH Grant/Contract )
U01CA062491 ( U.S. NIH Grant/Contract )
U01CA132194 ( U.S. NIH Grant/Contract )
080707 ( Other Identifier: CINJ )
First Posted: April 25, 2008    Key Record Dates
Results First Posted: December 18, 2014
Last Update Posted: December 18, 2014
Last Verified: August 2014

Keywords provided by National Cancer Institute (NCI):
prostate Cancer
adenocarcinoma of the prostate
stage IV prostate cancer
newly diagnosed stage IV prostate cancer

Additional relevant MeSH terms:
Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Genital Diseases, Male
Prostatic Diseases
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Retinol acetate
Gossypol acetic acid
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Androgen Antagonists
Hormone Antagonists
Antineoplastic Agents
Fertility Agents, Female
Fertility Agents
Reproductive Control Agents
Antineoplastic Agents, Hormonal
Adjuvants, Immunologic
Immunologic Factors
Anticarcinogenic Agents