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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

Phase 2
18 Years
Not Enrolling
Adenocarcinoma of the Prostate, Stage IV Prostate Cancer

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Trial Information

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


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.

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.


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.

Inclusion Criteria


- Newly diagnosed disease

- Baseline prostate-specific antigen (PSA) >= 5.0 ng/mL (within 12 weeks prior to

- 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

- 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

- 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

Type of Study:


Study Design:

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Percentage of patients with undetectable prostate-specific antigen (PSA) (< 0.2 ng/mL)

Outcome Time Frame:

At 7 months

Safety Issue:


Principal Investigator

Robert DiPaola

Investigator Role:

Principal Investigator

Investigator Affiliation:

Cancer Institute of New Jersey


United States: Food and Drug Administration

Study ID:




Start Date:

July 2009

Completion Date:

Related Keywords:

  • Adenocarcinoma of the Prostate
  • Stage IV Prostate Cancer
  • Adenocarcinoma
  • Adenocarcinoma, Mucinous
  • Prostatic Neoplasms



Cancer Institute of New JerseyNew Brunswick, New Jersey  08901
University of Wisconsin Hospital and ClinicsMadison, Wisconsin  53792-0001