A Study of Definitive Therapy to Treat Prostate Cancer

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 neoadjuvant androgen deprivation and up to 6 cycles of chemotherapy, (2nd) definitive local tumor control with prostatectomy +/- adjuvant radiation therapy, and (3rd) consolidative stereotactic radiation to oligometastatic lesions. The men will receive a total of 1 year of androgen deprivation. Androgen blockade will be the same throughout the course of treatment.

Detailed Description
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Neoadjuvant 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. Surgery and Radiation (month 7 though  11): After completion of neoadjuvant therapy, the men will be treated with definitive local therapy with radical prostatectomy (RP) +/- adjuvant radiation therapy (RT). After definitive local therapy, patients will be treated with consolidative stereotactic body radiation therapy (SBRT) to the metastatic sites. Follow up: Patients will continue on androgen deprivation for a total of 1 year. 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

Conditions
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Prostate Cancer

Intervention / Treatment
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* Drug: Leuprolide Acetate
* Drug: Bicalutamide
* Drug: Docetaxel
* Procedure: Prostatectomy
* Radiation: Radiation


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 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 prostatectomy +/- adjuvant radiation therapy, and (3rd) consolidative stereotactic radiation to oligometastatic lesions. Additionally, must be willing to be treated with a full year 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 scan) Able to swallow the study drugs whole as tablets Exclusion Criteria: Prior local therapy to treat prostate cancer (e.g. radical prostatectomy, 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) Cytochrome (CYP) -17 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 1 year 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 >upper limit of normal; aspartate aminotransferase , alanine aminotransferase > 2.5 x upper limit of normal) Creatinine clearance of ≥ 30 mL/min. 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<br>(1st) Systemic chemo-hormonal therapy with up to 6-months ( 24 weeks) of neoadjuvant androgen deprivation (Leuprolide Acetate) and up to 6 cycles of chemotherapy (Docetaxel), (2nd) definitive local tumor control with prostatectomy +/- adjuvant radiation therapy, and (3rd) consolidative stereotactic radiation to oligometastatic lesions. The men will receive a total of 1 year 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: Bicalutamide<br>* bicalutamide (Casodex) 50mg by mouth daily<br>* Other names: Casodex;Drug: Docetaxel<br>* Docetaxel (taxotere) 75 mg/m2 IV will be given on day 1 every 3 weeks, up to 6 cycles.<br>* Other names: Texotere;Procedure: Prostatectomy<br>* Removal of the entire prostate gland, plus some surrounding tissue.<br>* Other names: Radical prostatectomy;Radiation: Radiation<br>* 5 high dose radiation treatments to the metastatic (tumor has spread to other parts of the body) sites.<br>|

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety of the Multimodality Therapy as Assessed by Number of Participants With Neutropenia and Surgical or Radiation Toxicities | To assess the safety and therapeutic benefit of multimodality therapy in men presenting with newly diagnosed oligometastatic prostate cancer (<5 sites of metastases). Safety is defined as the incidence of Grades 3 and 4 neutropenia and surgical- or radiation-induced toxicities. Neutropenia is a lower than normal number of neutrophils (a type of white blood cell) in the blood. Although dependent on the specific laboratory, the normal number is of neutrophils is generally about 1500-7800 cells/microliter. Grade 3 and 4 neutropenia refer to neutrophil levels <1,000-500 and <500, respectively. The average risk of docetaxel-induced Grade 3 and 4 neutropenia is about 35%. During the course of the study, if we had seen evidence that the risk of Grade 3 and 4 neutropenia was >50%, the study would have been stopped. | 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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Lupron, Bicalutamide, Docetaxel