Gossypol and Androgen Ablation Therapy in Treating Patients With Newly Diagnosed Metastatic Prostate Cancer - Full Text View

Sponsor:	Cancer Institute of New Jersey
Collaborator:	National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00666666

Purpose

RATIONALE: Androgens can cause the growth of prostate cancer cells. Luteinizing hormone-releasing hormone agonists and drugs, such as bicalutamide, may lessen the amount of androgens made by the body. Sometimes when androgen ablation therapy is given, it does not stop the growth of tumor cells. The tumor is said to be resistant to androgen ablation therapy. Giving gossypol together with androgen ablation therapy may reduce drug resistance and stop the growth of tumor cells.

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.

Condition	Intervention	Phase
Prostate Cancer	Drug: R-(-)-gossypol acetic acid Drug: bicalutamide Drug: releasing hormone agonist therapy Genetic: protein expression analysis Genetic: western blotting Other: immunohistochemistry staining method Other: laboratory biomarker analysis	Phase II

Study Type:	Interventional
Study Design:	Treatment, Open Label
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:

MedlinePlus related topics: Cancer Prostate Cancer

Drug Information available for: Acetic acid Bicalutamide

U.S. FDA Resources

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 7 months [ Designated as safety issue: No ]

Secondary Outcome Measures:

Safety [ 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 during the first 7 months of therapy [ Designated as safety issue: No ]
Changes in Bcl-2 and Bax/Bak protein expression in peripheral blood mononuclear cells after treatment [ Designated as safety issue: No ]
Bcl-2 family protein expression in baseline tumor tissue [ Designated as safety issue: No ]

Estimated Enrollment:	55
Study Start Date:	April 2008
Estimated Primary Completion Date:	April 2010 (Final data collection date for primary outcome measure)

Detailed Description:

OBJECTIVES:

Primary

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

To determine the safety of this regimen in these patients.
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.
To determine changes in Bcl-2 and Bax/Bak protein expression in peripheral blood mononuclear cells after treatment.
To analyze Bcl-2 family protein expression in baseline tumor tissue.

OUTLINE: This is a multicenter study.

Patients receive oral R-(-)-gossypol (AT-101) once daily on days 1-21. Treatment repeats every 28 weeks for 8 courses in the absence of disease progression or unacceptable toxicity. Patients also receive androgen ablation therapy comprising a luteinizing hormone-releasing hormone agonist (as directed). Patients may receive oral bicalutamide once daily beginning 6 weeks before the initiation of AT-101 and continuing after completion of AT-101, at the discretion of the treating physician.

Peripheral blood mononuclear cells are collected at baseline and on day 21 and analyzed for Bcl-2, actin, Bax, and Bak protein expression by western blotting. Original tumor tissue blocks are analyzed for overexpression of Bcl-2 and other apoptotic proteins by immunohistochemistry.

Eligibility

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

Criteria

DISEASE CHARACTERISTICS:

Histologically confirmed adenocarcinoma of the prostate
- Clinical stage D2 disease, defined by soft tissue or bony metastasis
- 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

PATIENT CHARACTERISTICS:

ECOG performance status (PS) 0-2 OR Karnofsky PS 60-100%
Life expectancy > 6 months
Leukocytes ≥ 3,000/mcL
Absolute neutrophil count ≥ 1,500/mcL (without transfusion)
Platelet count ≥ 100,000/mcL (without transfusion)
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 including, but not limited to, any of the following:
- Ongoing or active infection
- Symptomatic congestive heart failure
- Unstable angina pectoris
- Cardiac arrhythmia
- 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

PRIOR CONCURRENT THERAPY:

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 prior surgical procedures affecting absorption
No prior bilateral orchiectomy
Other prior local surgery allowed
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

Contacts and Locations

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

Locations

United States, Michigan
University of Michigan Comprehensive Cancer Center	Recruiting
Ann Arbor, Michigan, United States, 48109-0942
Contact: Clinical Trials Office - University of Michigan Comprehensive 800-865-1125
United States, New Jersey
Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School	Recruiting
New Brunswick, New Jersey, United States, 08903
Contact: Clinical Trials Office - Cancer Institute of New Jersey 732-235-8675
United States, Wisconsin
University of Wisconsin Paul P. Carbone Comprehensive Cancer Center	Recruiting
Madison, Wisconsin, United States, 53792-6164
Contact: Clinical Trials Office - University of Wisconsin Paul P. Carbo 608-262-5223

Sponsors and Collaborators

Cancer Institute of New Jersey

National Cancer Institute (NCI)

Investigators

Principal Investigator:

Robert S. DiPaola, MD

Cancer Institute of New Jersey

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School ( Robert S. DiPaola )
Study ID Numbers:	CDR0000593497, CINJ-080707, CINJ-0220080008
Study First Received:	April 24, 2008
Last Updated:	August 6, 2009
ClinicalTrials.gov Identifier:	NCT00666666 History of Changes
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

stage IV prostate cancer
adenocarcinoma of the prostate

Additional relevant MeSH terms:

Prostatic Diseases
Genital Neoplasms, Male
Contraceptive Agents
Antineoplastic Agents
Hormone Antagonists
Physiological Effects of Drugs
Hormones, Hormone Substitutes, and Hormone Antagonists
Contraceptive Agents, Female
Urogenital Neoplasms
Reproductive Control Agents
Contraceptive Agents, Male
Hormones
Gossypol

Neoplasms by Site
Therapeutic Uses
Antispermatogenic Agents
Genital Diseases, Male
Gossypol acetic acid
Pharmacologic Actions
Neoplasms
Androgen Antagonists
Bicalutamide
Prostatic Neoplasms
Antineoplastic Agents, Phytogenic
Spermatocidal Agents
Androgens

ClinicalTrials.gov processed this record on February 09, 2010