A Study of Definitive Therapy to Treat Prostate Cancer After Prostatectomy

Study Overview
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Brief Summary
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To assess the safety of treating men with oligometastatic prostate cancer with the following therapy: (1st) Systemic chemo-hormonal therapy with up to 6-months ( 24 weeks) of adjuvant androgen deprivation and up to 6 cycles of chemotherapy, (2nd) definitive local tumor control with adjuvant radiation therapy, and (3rd) consolidative stereotactic radiation to oligometastatic lesions. The men will receive a total of 2 years of androgen deprivation. Androgen blockade will be the same throughout the course of treatment.

Detailed Description
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Adjuvant treatment (month 1 through  6): All patients will be treated with up to 6 months of androgen deprivation, plus up to 6 cycles of docetaxel chemotherapy. Following docetaxel therapy, patients with a Prostate-specific antigen response of at least a 50% decrease from baseline, will proceed to maximum consolidative therapy. Radiation (month 7 though  11): After completion of adjuvant chemotherapy, the men will be treated with definitive local therapy with adjuvant radiation therapy (RT). After definitive local therapy, patients will be treated with consolidative stereotactic body radiation therapy (SBRT) to the metastatic sites (if present). Follow up: Patients will continue on androgen deprivation for a total of 2 years. They will be followed clinically and monitored with serum testosterone and Prostate-specific antigen until 2-years after completion of ADT (Androgen deprivation therapy) treatment. Androgen blockade will be the same throughout the course of treatment.

Official Title
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A Phase II Study of Definitive Therapy for Newly Diagnosed Men With Oligometastatic Prostate Cancer After Prostatectomy

Conditions
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Prostate Cancer

Intervention / Treatment
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* Drug: Leuprolide Acetate
* Drug: Docetaxel
* Drug: Bicalutamide
* Radiation: Radiation
* Drug: Abiraterone Acetate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Willing and able to provide written informed consent. Age ≥ 18 years Eastern cooperative oncology group (ECOG) performance status ≤2 Documented histologically confirmed adenocarcinoma of the prostate Willing to undergo the following therapy: (1st) Systemic chemo-hormonal therapy with up to 6-months ( 24 weeks) of neoadjuvant androgen deprivation and up to 6 cycles of chemotherapy, (2nd) definitive local tumor control with adjuvant radiation therapy, and (3rd) consolidative stereotactic radiation to oligometastatic lesions. Additionally, must be willing to be treated with a full two years of androgen deprivation. Oligometastatic prostate cancer: Stage T1-4, N0-1 and/or M1a-b (up to 5 metastatic lesions- including bone lesions and non-regional lymph nodes seen on bone scan, contrast enhanced CT scan, or positron emission tomography PET scan) Exclusion Criteria: Prior local non-surgical therapy to treat prostate cancer (e.g. radiation therapy, brachytherapy) Prior therapy to a metastatic site. Prior or ongoing systemic therapy for prostate cancer including, but not limited to: Hormonal therapy (e.g. leuprolide, goserelin, triptorelin, degarelix) CYP-17 (cytochrome P450 17α-hydroxy/17,20-lyase) inhibitors (e.g. ketoconazole) Antiandrogens (e.g. bicalutamide, nilutamide) Second generation antiandrogens (e.g. enzalutamide, abiraterone) Immunotherapy (e.g. sipuleucel-T, ipilimumab) Chemotherapy (e.g. docetaxel, cabazitaxel) *Note: may be enrolled if hormone therapy was recently initiated (<90 days duration)). In the event that hormone therapy was initiated prior to study enrollment, the clock for 2 years of androgen deprivation would begin at the time of therapy initiation, rather than at study enrollment. Evidence of serious and/or unstable pre-existing medical, psychiatric or other condition (including laboratory abnormalities) that could interfere with patient safety or provision of informed consent to participate in this study. Any psychological, familial, sociological, or geographical condition that could potentially interfere with compliance with the study protocol and follow-up schedule. Abnormal bone marrow function [absolute neutrophil count (ANC)<1500/mm3, platelet count <100,000/mm3, hemoglobin <9 g/dL] Abnormal liver function (bilirubin >ULN ( upper limit of normal); AST (aspartate aminotransferase), ALT (alanine transaminase) > 2.5 x upper limit of normal) Creatinine clearance of ≥ 30 mL/min. CrCl (Creatinine clearance) should be calculated suing the Cockcroft-Gault formula. Active cardiac disease defined as active angina, symptomatic congestive heart failure, or myocardial infarction within previous six months. Prior history of malignancy in the past 3 years with the exception of basal cell and squamous cell carcinoma of the skin. Other malignancies that are considered to have a low potential to progress may be enrolled at discretion of PI.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: chemohormonal and definitive therapy after prostatectomy<br>(1st) Systemic chemo-hormonal therapy with up to 6-months ( 24 weeks) of adjuvant androgen deprivation (Leuprolide Acetate) and up to 6 cycles of chemotherapy (Docetaxel), (2nd) definitive local tumor control with adjuvant radiation therapy, and (3rd) consolidative stereotactic radiation to oligometastatic lesions. The men will receive a total of 2 years of androgen deprivation. Androgen blockade (Bicalutamide) will be the same throughout the course of treatment. | Drug: Leuprolide Acetate<br>* 22.5mg by intramuscular (IM) injection every 3 months<br>* Other names: Lupron Deport;Drug: Docetaxel<br>* 75 mg/m2 IV will be given on day 1 every 3 weeks, up to 6 cycles. Dose may decreased in the following intervals: 65 mg/M2, 55 mg/M2, 35 mg/M2.<br>* Other names: Texotere;Drug: Bicalutamide<br>* bicalutamide (Casodex) 50mg by mouth daily<br>* Other names: Casodex;Radiation: Radiation<br>* Radiation will be delivered in 1 to 5 fractions, and the dose and fractionation schedule will depend on the size and location of the lesion and the surrounding normal tissue constraints in accordance with AAPM Task Group 101 recommendations. Typical doses include 16 - 24 Gy in 1 fraction, 48 - 50 Gy in 4 fractions, and 50 - 60 Gy in 5 fractions.<br>Drug: Abiraterone Acetate<br>* Abiraterone acetate 1000 mg / day may be given at the investigator's discretion.<br>* Other names: Zytiga;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy as Assessed by 3-year Prostate-specific Antigen Progression-free Survival Rate | To evaluate efficacy of multimodality therapy in men, defined as the 3 year Prostate-specific antigen progression-free (Prostate-specific antigen<0.2 ng/ml) survival rate among men who have non-castrate testosterone levels 2 years after enrollment. | 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety of the 3 Years Multimodality Therapy Assessed Using Common Terminology Criteria for Adverse Events (CTCAE) Version 4 Criteria and the Clavien-Dindo Classification | To assess the safety of multimodality therapy in men presenting with newly diagnosed oligometastatic prostate cancer after prostatectomy. Toxicities related to neoadjuvant therapy, radiation therapy, or stereotactic body radiation therapy (SBRT) will be assessed using CTCAE version 4 criteria. Surgical toxicities will be assessed using the Clavien-Dindo Classification | 3 years | 
| Time to Prostate-specific Antigen Recurrence | To investigate the time from an undetectable Prostate-specific antigen (≤0.2 ng/mL) until the Prostate-specific antigen is >0.2 over two time-points. | 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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prostatectomy, androgen deprivation, chemotherapy, radiation