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

NCT00666666 | Completed Phase 2 Results

• 6 other identifiers: NCI-2009-002648014N01CM62201U01CA062491U01CA132194080707
• Study Type: interventional
• Target: 55
• Locations: 1 country
• Sites: 4

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

Conditions

Adenocarcinoma of the Prostate; Stage IV Prostate Cancer

Keywords

prostate Cancer; adenocarcinoma of the prostate; stage IV prostate cancer; newly diagnosed stage IV prostate cancer

Outcome Measures

Primary Outcomes (1)

• Percentage of Patients With Undetectable Prostate-specific Antigen (PSA) (< 0.2 ng/mL) at End of 7 Cycles

  3 years

Secondary Outcomes (2)

• Percentage of Patients With PSA ≥ 0.2 ng/mL But < 4.0 ng/mL

  3 years

• Percentage of Patients With Overall PSA < 4.0 ng/mL

  3 years

Study Arms (1)

AT101 (R-(-)-gossypol acetic acid)

EXPERIMENTAL

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; Drug: Bicalutamide; Other: LHRH agent

Interventions

AT-101 DRUG

AT101 will be administered orally 20 mg/day for 21 days of a 28 day cycle.

Also known as: R-(-)-gossypol acetic acid

AT101 (R-(-)-gossypol acetic acid)

Bicalutamide DRUG

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.

Also known as: Casodex, CDX

AT101 (R-(-)-gossypol acetic acid)

LHRH agent OTHER

An LHRH agonist(Leuprolide Acetate or Goserelin)can be administered at standard dosing appropriate to the agent used.

Also known as: Leutinizing Hormone Receptor Hormone agonist

AT101 (R-(-)-gossypol acetic acid)

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (4)

University of Chicago

Chicago, Illinois, 60637, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

Cancer Institute of New Jersey

New Brunswick, New Jersey, 08903, United States

Location

University of Wisconsin Hospital and Clinics

Madison, Wisconsin, 53792, United States

Location

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

gossypol acetic acid; bicalutamide

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Results Point of Contact

• Title: Robert DiPaola, MD
• Organization: Rutgers Cancer Institute of New Jersey

zelinsta@cinj.rutgers.edu, dipaolrs@cinj.rutgers.edu, rizzoji@cinj.rutgers.edu

732-235-8675

Study Officials

• Robert DiPaola

  Rutgers Cancer Institute of New Jersey

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 24, 2008
• First Posted: April 25, 2008
• Study Start: July 1, 2009
• Primary Completion: May 1, 2011
• Study Completion: June 1, 2012
• Last Updated: December 18, 2014
• Results First Posted: December 18, 2014

Record last verified: 2014-08

Locations

US (4)