Phase II-III Trial of Adjuvant Radiotherapy and Androgen Deprivation Following Radical Prostatectomy With or Without Adjuvant Docetaxel
Overview
- Phase
- Phase 2
- Intervention
- Flutamide
- Conditions
- Stage I Prostate Adenocarcinoma AJCC v7
- Sponsor
- NRG Oncology
- Enrollment
- 612
- Locations
- 409
- Primary Endpoint
- Freedom from progression (FFP) (Phase II)
- Status
- Completed
- Last Updated
- 3 months ago
Overview
Brief Summary
This randomized phase II/III trial studies docetaxel, antiandrogen therapy, and radiation therapy to see how well it works compared with antiandrogen therapy and radiation therapy alone in treating patients with prostate cancer that has been removed by surgery. Androgen can cause the growth of prostate cells. Antihormone therapy may lessen the amount of androgen made by the body. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Drugs used in chemotherapy, such as docetaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving antiandrogen therapy and radiation therapy with or without docetaxel after surgery may kill any remaining tumor cells.
Detailed Description
PRIMARY OBJECTIVE: I. To assess the benefit of docetaxel as measured by improvement in freedom from progression (phase II) and subsequently metastasis free survival (phase III) when given in combination with radiation and androgen deprivation in treatment of high risk prostate cancer post-radical prostatectomy. SECONDARY OBJECTIVES: I. To assess overall survival. II. To assess local time to progression. III. To assess undetectable prostate-specific antigen (PSA) with a non-castrate testosterone at 2.5 years post treatment. IV. To assess the utility of genomic profiling in making adjuvant therapy decisions post-prostatectomy. V. To assess toxicity of docetaxel in the post-operative setting when combined with radiation and androgen deprivation therapy. VI. To assess treatment response by genomically defined sub-groups of prostate cancer patients. EXPLORATORY OBJECTIVE: I. To optimize quality assurance methodologies and processes for radiotherapy and imaging, with machine learning strategies. OUTLINE: Patients are randomized to 1 of 2 arms. ARM I: Patients receive androgen deprivation therapy comprising leuprolide acetate, goserelin acetate, degarelix, bicalutamide, flutamide, or nilutamide for 6 months. Beginning 8 weeks after the start of androgen deprivation therapy, patients receive external beam radiation therapy (EBRT) for 7.5 weeks. ARM II: Patients receive androgen deprivation therapy and EBRT as in Arm I. Within 4-6 weeks after completion of radiation therapy, patients receive docetaxel intravenously (IV) over 1 hour on day 1 of every 21 days for 6 cycles in the absence of disease progression or unexpected toxicity. After completion of study treatment, patients are followed up every 3 months for 2 years, then every 6 months for 3 years, and then yearly.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Patients post-prostatectomy with baseline Gleason \>= 7 (per prostatectomy pathology)
- •Baseline PSA prior to start of androgen deprivation therapy nadir \>= 0.2 ng/ml (post-operative value is never undetectable) obtained prior to step 1 registration
- •Baseline testosterone level obtained post-prostatectomy prior to start of androgen deprivation therapy and prior to step 1 registration
- •Pathologically (histologically) proven diagnosis of adenocarcinoma of the prostate as confirmed at time of prostatectomy; prostatectomy must have been performed within 365 days (1 year) prior to step 1 registrationand any type of radical prostatectomy is permitted, including retropubic, perineal, laparoscopic or robotically assisted; (please note: Prior ablative treatment for benign prostatic hypertrophy or focal high-intensity focused ultrasound therapy \[HIFU\] prior to prostatectomy is allowed)
- •Surgical formalin-fixed paraffin-embedded (FFPE) specimen must be available for submission to GenomeDx for genomic analysis on DECIPHER GRID platform
- •Please note: If a patient already has a Decipher risk score and meets all of the other eligibility criteria, the patient is eligible to be registered; however, the Decipher risk report will need to be submitted to GenomeDx for validation
- •Prior androgen deprivation (luteinizing hormone-releasing hormone \[LHRH\] agonist and/or non-steroidal anti-androgen) is allowed if:
- •Androgen deprivation therapy was initiated within 30 days prior to study enrollment
- •Androgen deprivation therapy was given for ≤ 90 days duration prior to radical prostatectomy
- •Please note: Finasteride or dutasteride must be stopped before treatment but should not determine eligibility
Exclusion Criteria
- •Definitive clinical or radiologic evidence of metastatic disease
- •Prior invasive malignancy (except non-melanomatous skin cancer or other in-situ malignancies, or stage Ta bladder cancer) unless disease free for a minimum of 2 years
- •Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields
- •Prior systemic chemotherapy for the study cancer; note that prior chemotherapy for a different cancer is allowable if completed more than two years prior to step 1 registration; prior androgen deprivation is allowed
- •Prior whole gland ablative therapy (i.e. cryoablation or high intensity focused ultrasound \[HIFU\]) for prostate cancer is not allowed
- •Prostatectomy performed greater than 365 days (1 year) prior to step 1 registration
- •Severe and/or active co-morbidity defined as follows:
- •History of inflammatory bowel disease
- •History of active hepatitis B or C; blood tests are not required to determine if the patient has had hepatitis B or C, unless the patient reports a history of hepatitis
- •Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months
Arms & Interventions
Arm I (androgen deprivation therapy, EBRT)
Patients receive androgen deprivation therapy comprising leuprolide acetate, goserelin acetate, degarelix, bicalutamide, flutamide, or nilutamide for 6 months. Beginning 8 weeks after the start of androgen deprivation therapy, patients receive EBRT for 7.5 weeks.
Intervention: Flutamide
Arm I (androgen deprivation therapy, EBRT)
Patients receive androgen deprivation therapy comprising leuprolide acetate, goserelin acetate, degarelix, bicalutamide, flutamide, or nilutamide for 6 months. Beginning 8 weeks after the start of androgen deprivation therapy, patients receive EBRT for 7.5 weeks.
Intervention: Goserelin
Arm I (androgen deprivation therapy, EBRT)
Patients receive androgen deprivation therapy comprising leuprolide acetate, goserelin acetate, degarelix, bicalutamide, flutamide, or nilutamide for 6 months. Beginning 8 weeks after the start of androgen deprivation therapy, patients receive EBRT for 7.5 weeks.
Intervention: Bicalutamide
Arm I (androgen deprivation therapy, EBRT)
Patients receive androgen deprivation therapy comprising leuprolide acetate, goserelin acetate, degarelix, bicalutamide, flutamide, or nilutamide for 6 months. Beginning 8 weeks after the start of androgen deprivation therapy, patients receive EBRT for 7.5 weeks.
Intervention: Degarelix
Arm I (androgen deprivation therapy, EBRT)
Patients receive androgen deprivation therapy comprising leuprolide acetate, goserelin acetate, degarelix, bicalutamide, flutamide, or nilutamide for 6 months. Beginning 8 weeks after the start of androgen deprivation therapy, patients receive EBRT for 7.5 weeks.
Intervention: External Beam Radiation Therapy
Arm I (androgen deprivation therapy, EBRT)
Patients receive androgen deprivation therapy comprising leuprolide acetate, goserelin acetate, degarelix, bicalutamide, flutamide, or nilutamide for 6 months. Beginning 8 weeks after the start of androgen deprivation therapy, patients receive EBRT for 7.5 weeks.
Intervention: Goserelin Acetate
Arm I (androgen deprivation therapy, EBRT)
Patients receive androgen deprivation therapy comprising leuprolide acetate, goserelin acetate, degarelix, bicalutamide, flutamide, or nilutamide for 6 months. Beginning 8 weeks after the start of androgen deprivation therapy, patients receive EBRT for 7.5 weeks.
Intervention: Laboratory Biomarker Analysis
Arm I (androgen deprivation therapy, EBRT)
Patients receive androgen deprivation therapy comprising leuprolide acetate, goserelin acetate, degarelix, bicalutamide, flutamide, or nilutamide for 6 months. Beginning 8 weeks after the start of androgen deprivation therapy, patients receive EBRT for 7.5 weeks.
Intervention: Leuprolide
Arm I (androgen deprivation therapy, EBRT)
Patients receive androgen deprivation therapy comprising leuprolide acetate, goserelin acetate, degarelix, bicalutamide, flutamide, or nilutamide for 6 months. Beginning 8 weeks after the start of androgen deprivation therapy, patients receive EBRT for 7.5 weeks.
Intervention: Leuprolide Acetate
Arm I (androgen deprivation therapy, EBRT)
Patients receive androgen deprivation therapy comprising leuprolide acetate, goserelin acetate, degarelix, bicalutamide, flutamide, or nilutamide for 6 months. Beginning 8 weeks after the start of androgen deprivation therapy, patients receive EBRT for 7.5 weeks.
Intervention: Nilutamide
Arm II (androgen deprivation therapy, EBRT, docetaxel)
Patients receive androgen deprivation therapy and EBRT as in Arm I. Within 4-6 weeks after completion of radiation therapy, patients receive docetaxel IV over 1 hour on day 1 of every 21 days for 6 cycless in the absence of disease progression or unexpected toxicity.
Intervention: Bicalutamide
Arm II (androgen deprivation therapy, EBRT, docetaxel)
Patients receive androgen deprivation therapy and EBRT as in Arm I. Within 4-6 weeks after completion of radiation therapy, patients receive docetaxel IV over 1 hour on day 1 of every 21 days for 6 cycless in the absence of disease progression or unexpected toxicity.
Intervention: Degarelix
Arm II (androgen deprivation therapy, EBRT, docetaxel)
Patients receive androgen deprivation therapy and EBRT as in Arm I. Within 4-6 weeks after completion of radiation therapy, patients receive docetaxel IV over 1 hour on day 1 of every 21 days for 6 cycless in the absence of disease progression or unexpected toxicity.
Intervention: Docetaxel
Arm II (androgen deprivation therapy, EBRT, docetaxel)
Patients receive androgen deprivation therapy and EBRT as in Arm I. Within 4-6 weeks after completion of radiation therapy, patients receive docetaxel IV over 1 hour on day 1 of every 21 days for 6 cycless in the absence of disease progression or unexpected toxicity.
Intervention: External Beam Radiation Therapy
Arm II (androgen deprivation therapy, EBRT, docetaxel)
Patients receive androgen deprivation therapy and EBRT as in Arm I. Within 4-6 weeks after completion of radiation therapy, patients receive docetaxel IV over 1 hour on day 1 of every 21 days for 6 cycless in the absence of disease progression or unexpected toxicity.
Intervention: Flutamide
Arm II (androgen deprivation therapy, EBRT, docetaxel)
Patients receive androgen deprivation therapy and EBRT as in Arm I. Within 4-6 weeks after completion of radiation therapy, patients receive docetaxel IV over 1 hour on day 1 of every 21 days for 6 cycless in the absence of disease progression or unexpected toxicity.
Intervention: Goserelin
Arm II (androgen deprivation therapy, EBRT, docetaxel)
Patients receive androgen deprivation therapy and EBRT as in Arm I. Within 4-6 weeks after completion of radiation therapy, patients receive docetaxel IV over 1 hour on day 1 of every 21 days for 6 cycless in the absence of disease progression or unexpected toxicity.
Intervention: Goserelin Acetate
Arm II (androgen deprivation therapy, EBRT, docetaxel)
Patients receive androgen deprivation therapy and EBRT as in Arm I. Within 4-6 weeks after completion of radiation therapy, patients receive docetaxel IV over 1 hour on day 1 of every 21 days for 6 cycless in the absence of disease progression or unexpected toxicity.
Intervention: Laboratory Biomarker Analysis
Arm II (androgen deprivation therapy, EBRT, docetaxel)
Patients receive androgen deprivation therapy and EBRT as in Arm I. Within 4-6 weeks after completion of radiation therapy, patients receive docetaxel IV over 1 hour on day 1 of every 21 days for 6 cycless in the absence of disease progression or unexpected toxicity.
Intervention: Leuprolide
Arm II (androgen deprivation therapy, EBRT, docetaxel)
Patients receive androgen deprivation therapy and EBRT as in Arm I. Within 4-6 weeks after completion of radiation therapy, patients receive docetaxel IV over 1 hour on day 1 of every 21 days for 6 cycless in the absence of disease progression or unexpected toxicity.
Intervention: Leuprolide Acetate
Arm II (androgen deprivation therapy, EBRT, docetaxel)
Patients receive androgen deprivation therapy and EBRT as in Arm I. Within 4-6 weeks after completion of radiation therapy, patients receive docetaxel IV over 1 hour on day 1 of every 21 days for 6 cycless in the absence of disease progression or unexpected toxicity.
Intervention: Nilutamide
Outcomes
Primary Outcomes
Freedom from progression (FFP) (Phase II)
Time Frame: From time of randomization to first event, assessed up to 43 months
Will be determined with a one-sided stratified log-rank test when 89 FFP events have been observed. Both unadjusted and adjusted hazard ratios and the respective 95% confidence interval will be computed. Events for FFP will be the first occurrence of biochemical failure by prostate specific antigen (PSA) \>= 0.4 ng/ml over the nadir PSA confirmed by a second PSA higher than the first by any amount, recurrence (local, regional or distant), institution of secondary androgen deprivation therapy and death from any cause.
Metastasis free survival (MFS) (Phase III)
Time Frame: From time of randomization to first occurrence of distant metastasis or death from any cause, assessed up to 9.5 years
Will be measured with a one-sided stratified log-rank test when 282 MFS events have been observed. Both unadjusted and adjusted hazard ratios and the respective 95% confidence interval will be computed.
Secondary Outcomes
- Proportion of undetectable prostate specific antigen (PSA) with a non-castrate testosterone(At 2.5 years)
- Overall survival(Time to death from any cause assessed up to 2.5 years)
- Time to local progression(Baseline to local or regional recurrence ignoring biochemical failure and distant recurrence and censoring for death, assessed up to 2.5 years)
- Late grade 3+ adverse events scored according to the Cancer Therapy Evaluation Program active version of the Common Terminology Criteria for Adverse Events(From protocol treatment starts to the worst late grade 3+ adverse event, assessed up to 9 years)
- Incidence of acute adverse events scored according to the Cancer Therapy Evaluation Program active version of the Common Terminology Criteria for Adverse Events(Up to 30 days post radiation therapy)
- Genomic profiling in making adjuvant therapy decisions(Up to 9 years)