Phase II Trial of Radiation With Androgen Deprivation: Abiraterone Acetate, Prednisone and Luteinizing Hormone Releasing Hormone Agonist Prior to Radiation Therapy
Overview
- Phase
- Phase 2
- Intervention
- abiraterone acetate
- Conditions
- Adenocarcinoma of the Prostate
- Sponsor
- University of Washington
- Enrollment
- 24
- Locations
- 2
- Primary Endpoint
- 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
- Status
- Completed
- Last Updated
- 8 years ago
Overview
Brief Summary
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.
Detailed Description
PRIMARY OBJECTIVES: I. To evaluate the safety of abiraterone (abiraterone acetate) and prednisone with luteinizing hormone-releasing hormone 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. SECONDARY OBJECTIVES: I. To determine whether treatment with abiraterone acetate with luteinizing releasing hormone agonist will be more effective than 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 progression in patients treated with GnRH agonist with abiraterone acetate. OUTLINE: Patients receive abiraterone acetate orally and prednisone once daily 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.
Investigators
Bruce Montgomery
Principal Investigator
University of Washington
Eligibility Criteria
Inclusion Criteria
- •Willing and able to provide written informed consent
- •Patients must allow biopsy prior to neoadjuvant therapy and at the time of fiducial placement
- •Written Authorization for Use and Release of Health and Research Study Information has been obtained
- •Histologically proven adenocarcinoma of the prostate
- •Patients must be candidates for short or long term androgen deprivation in combination with external beam radiotherapy (RT) based on the following criteria:
- •Intermediate Risk Disease: T2b/c, or Gleason 7, or Prostate Specific Antigen 10-20
- •High Risk Disease: Gleason 8-10, or Prostate specific antigen\> 20, or T3/4
- •Patients may not have received any prior pharmacologic therapy or radiation therapy (RT) for prostate cancer
- •Eastern Cooperative Oncology Group (ECOG) performance status =\< 2
- •Karnofsky \>= 60%
Exclusion Criteria
- •Patients may not be receiving any investigational agents
- •Concurrent enrollment in another clinical investigational drug or device study is prohibited
- •The concurrent administration of other anticancer therapy, including cytotoxic or hormonal agents (except Luteinizing hormone releasing hormone agonists), or immunotherapy, is prohibited during neoadjuvant concurrent and adjuvant therapy
- •Patients who are currently receiving active therapy for other neoplastic disorders will not be eligible
- •Patients with histologic evidence of small cell carcinoma of the prostate will not be eligible
- •Patients with hypogonadism or severe androgen deficiency as defined by serum testosterone less than 100 ng/dL will not be eligible
- •History of pituitary or adrenal dysfunction
- •Patients who are receiving any androgens, estrogens or progestational agents, or who received any of these agents within the 6 months prior to evaluation will not be eligible
- •Patients who are taking drugs which affect androgen metabolism (e.g. spironolactone, ketoconazole, finasteride, dutasteride) will not be eligible
- •Concomitant therapy with any of the following listed is prohibited: 5 alpha-reductase inhibitor (finasteride, dutasteride); ketoconazole, diethylstilbestrol, and other preparations such as saw palmetto thought to have endocrine effects on prostate cancer; radiopharmaceuticals such as strontium (89Sr) or samarium (153Sm); Aldactone, Spironol (spironolactone); estrogens, testosterone, progesterones, herbal medications
Arms & Interventions
Treatment (antihormone therapy and radiation therapy)
Patients receive abiraterone acetate and prednisone daily 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.
Intervention: abiraterone acetate
Treatment (antihormone therapy and radiation therapy)
Patients receive abiraterone acetate and prednisone daily 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.
Intervention: prednisone
Treatment (antihormone therapy and radiation therapy)
Patients receive abiraterone acetate and prednisone daily 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.
Intervention: leuprolide acetate
Treatment (antihormone therapy and radiation therapy)
Patients receive abiraterone acetate and prednisone daily 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.
Intervention: laboratory biomarker analysis
Treatment (antihormone therapy and radiation therapy)
Patients receive abiraterone acetate and prednisone daily 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.
Intervention: external beam radiation therapy
Treatment (antihormone therapy and radiation therapy)
Patients receive abiraterone acetate and prednisone daily 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.
Intervention: goserelin acetate
Outcomes
Primary Outcomes
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
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 3.0he 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
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 Luteinizing hormone releasing hormone agonist and bicalutamide as part of standard of care.
Secondary Outcomes
- Median Time to Prostate Specific Antigen Progression(6 months)