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
18 Years
N/A
Male
Adenocarcinoma of the Prostate, Stage IV Prostate Cancer
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
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.
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.
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.
Inclusion Criteria
Criteria:
- 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
- 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
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
- 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
treatment
- 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:
Interventional
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:
No
Principal Investigator
Robert DiPaola
Investigator Role:
Principal Investigator
Investigator Affiliation:
Cancer Institute of New Jersey
Authority:
United States: Food and Drug Administration
Study ID:
NCI-2009-00264
NCT ID:
NCT00666666
Start Date:
July 2009
Completion Date:
Related Keywords:
- Adenocarcinoma of the Prostate
- Stage IV Prostate Cancer
- Adenocarcinoma
- Adenocarcinoma, Mucinous
- Prostatic Neoplasms
Name | Location |
|---|---|
| Cancer Institute of New Jersey | New Brunswick, New Jersey 08901 |
| University of Wisconsin Hospital and Clinics | Madison, Wisconsin 53792-0001 |
