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 17, 2014
Last verified: August 2014
  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: AT-101
Drug: Bicalutamide
Other: LHRH agent
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) at End of 7 Cycles [ Time Frame: 3 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Percentage of Patients With PSA ≥ 0.2 ng/mL But < 4.0 ng/mL [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • Percentage of Patients With Overall PSA < 4.0 ng/mL [ Time Frame: 3 years ] [ Designated as safety issue: No ]

Enrollment: 55
Study Start Date: July 2009
Study Completion Date: June 2012
Primary Completion Date: May 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

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

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00666666

Locations
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
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, 080707
Study First Received: April 24, 2008
Results First Received: October 8, 2013
Last Updated: December 17, 2014
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

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:
Adenocarcinoma
Prostatic Neoplasms
Carcinoma
Genital Diseases, Male
Genital Neoplasms, Male
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Glandular and Epithelial
Prostatic Diseases
Urogenital Neoplasms
Bicalutamide
Gossypol
Gossypol acetic acid
Androgen Antagonists
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Antispermatogenic Agents
Contraceptive Agents
Contraceptive Agents, Female
Contraceptive Agents, Male
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Pharmacologic Actions
Physiological Effects of Drugs
Reproductive Control Agents
Spermatocidal Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on July 01, 2015