Abiraterone Acetate, Prednisone, and Leuprolide Acetate or Goserelin Before and During Radiation Therapy in Treating Patients With Localized or Locally Advanced Prostate Cancer
This phase II trial studies the side effects and how well abiraterone acetate, prednisone, and leuprolide acetate or goserelin before and during radiation therapy works in treating patients with localized or locally advanced prostate cancer. Androgens can cause the growth of prostate cancer cells. Antihormone therapy, such as abiraterone acetate, leuprolide acetate, and goserelin, may lessen the amount of androgens made by the body. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving abiraterone acetate and leuprolide acetate or goserelin before or together with radiation therapy may be an effective treatment for prostate cancer.
Adenocarcinoma of the Prostate
Stage IIA Prostate Cancer
Stage IIB Prostate Cancer
Stage III Prostate Cancer
Stage IV Prostate Cancer
Drug: abiraterone acetate
Drug: leuprolide acetate
Other: laboratory biomarker analysis
Radiation: external beam radiation therapy
Drug: goserelin acetate
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase II Trial of Radiation With Androgen Deprivation (RAD): Abiraterone Acetate, Prednisone and LHRH Agonist Prior to Radiation Therapy|
- Incidence of acute and chronic grade 3 or greater toxicity as evaluated using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 3.0 [ Time Frame: Up to 24 months after initiation of radiation therapy ] [ Designated as safety issue: Yes ]The distribution of time to late adverse events (observed severities of adverse events over time) will be estimated using the Kaplan-Meier method.
- Levels of dihydrotestosterone (DHT) and testosterone in prostate biopsy sample assessed by mass spectrometry [ Time Frame: Week 12 ] [ Designated as safety issue: No ]The levels from patients treated in this study will be compared to a control set of biopsies acquired from a separate but similar population of men with intermediate and high risk prostate cancer treated with three months of combined LHRH agonist and bicalutamide as part of standard of care.
- Inhibition of androgen-regulated gene expression and increased apoptotic cell death [ Time Frame: Week 12 ] [ Designated as safety issue: No ]Assessed by immunohistochemistry, cDNA microarray analysis, RT-PCR for androgen regulated genes (PSA, FKBP5, NKX3.1, AR, clusterin, acid phosphatase) from prostate biopsy samples.
- Median time to PSA progression [ Time Frame: 6 months ] [ Designated as safety issue: No ]Defined as the date of an increase of 2ng/mL or more above the PSA nadir achieved after completion of RT with the date of progression defined as the date on which that PSA was measured. Distribution of time-to-event variables will be estimated using the Kaplan-Meier product-limit method. Estimated with two-sided 95% confidence intervals.
- Median time to PSA progression [ Time Frame: 12 months ] [ Designated as safety issue: No ]Defined as the date of an increase of 2ng/mL or more above the PSA nadir achieved after completion of RT with the date of progression defined as the date on which that PSA was measured. Distribution of time-to-event variables will be estimated using the Kaplan-Meier product-limit method. Estimated with two-sided 95% confidence intervals.
|Study Start Date:||March 2010|
|Estimated Primary Completion Date:||September 2015 (Final data collection date for primary outcome measure)|
Experimental: Treatment (antihormone therapy and radiation therapy)
Patients receive abiraterone acetate PO and prednisone PO QD for 24 weeks. Patients also receive leuprolide acetate or goserelin in weeks 1 and 13. Patients undergo external beam radiotherapy starting in week 15 for 8.5 weeks. Treatment continues in the absence of disease progression or unacceptable toxicity.
Drug: abiraterone acetate
Other Names:Drug: prednisone
Other Names:Drug: leuprolide acetate
Given via injection
Other Names:Other: laboratory biomarker analysis
Correlative studyRadiation: external beam radiation therapy
Other Name: EBRTDrug: goserelin acetate
Given via injection
I. To evaluate the safety of abiraterone (abiraterone acetate) and prednisone with luteinizing hormone-releasing hormone (LHRH) agonist given as neoadjuvant and concurrent therapy with external beam radiation in patients with localized prostate cancer.
II. To determine whether pharmacologic suppression of the prostatic androgen axis by inhibition of androgen production with abiraterone can decrease tissue androgen levels to below those observed with gonadotropin-releasing hormone (GnRH) agonist suppression of testicular androgens.
I. To determine whether treatment with abiraterone acetate with LHRH agonist will be more effective than LHRH agonist with bicalutamide in inducing inhibition of androgen-regulated gene expression and increased apoptotic cell death as assessed by immunohistochemistry, complementary deoxyribonucleic acid (cDNA) microarray analysis and reverse transcription-polymerase chain reaction (RT-PCR).
II. To evaluate time to prostate-specific antigen (PSA) progression in patients treated with LHRH agonist with abiraterone acetate.
Patients receive abiraterone acetate orally (PO) and prednisone PO once daily (QD) for 24 weeks. Patients also receive leuprolide acetate or goserelin in weeks 1 and 13. Patients undergo external beam radiotherapy starting in week 15 for 8.5 weeks. Treatment continues in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 3 months for 5 years.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01023061
|United States, Washington|
|Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium|
|Seattle, Washington, United States, 98109|
|MultiCare Regional Cancer Center - Tacoma|
|Tacoma, Washington, United States, 98405|
|Principal Investigator:||Robert Montgomery||Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium|