Phase II-III Trial of Adjuvant Radiotherapy and Androgen Deprivation Following Radical Prostatectomy With or Without Adjuvant Docetaxel
Phase II-III Trial of Adjuvant Radiotherapy and Androgen Deprivation Following Radical Prostatectomy With or Without Adjuvant Docetaxel
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.
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.
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
Prior androgen deprivation (luteinizing hormone-releasing hormone [LHRH] agonist and/or non-steroidal anti-androgen) is allowed if:
Pathologically lymph node negative by pelvic lymphadenectomy (pN0) or lymph node status pathologically unknown (undissected pelvic lymph nodes [pNx])
Any pT-stage based on American Joint Committee on Cancer 7th edition eligible; study entry will be based on the following diagnostic workup:
History/physical examination within 60 days prior to step 1 registration
Negative distant metastatic workup:
Eastern Cooperative Oncology Group (ECOG) performance status of =< 1 within 60 days prior to step 1 registration
Platelets >= 100,000 cell/mm^3 (within 60 days prior to step 1 registration based upon a complete blood count [CBC])
Hemoglobin >= 10.0 g/dl (Note: The use of transfusion or other intervention to achieve hemoglobin [Hgb] >= 10.0 g/dl is NOT allowed) (within 60 days prior to step 1 registration based upon a CBC)
Absolute neutrophil count >= 1500 cells/mm^3 (within 60 days prior to step 1 registration based upon a CBC)
Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) < 1.5 x the upper limit of normal (within 60 days prior to step 1 registration)
Total bilirubin (=< 1.5 mg/dl) normal unless history of Gilbert's syndrome (within 60 days prior to step 1 registration)
The patient or a legally authorized representative must provide study-specific informed consent prior to step 1 registration
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:
Human immunodeficiency virus (HIV) positive with cluster of differentiation 4 (CD4) count < 200 cells/microliter; note that patients who are HIV positive are eligible, provided they are under treatment with highly active antiretroviral therapy (HAART) and have a CD4 count >= 200 cells/microliter within 30 days prior to step 1 registration; note also that HIV testing is not required for eligibility for this protocol
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