Denosumab Plus Enzalutamide, Abiraterone and Prednisone Compared to Denosumab Plus Enzalutamide Alone for Men With Castrate Resistant Prostate Cancer (CRPC) With Bone Metastases

Study Overview
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Brief Summary
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This is a correlative study to characterize serum metabolites associated with bone deposition, growth and turnover in patients with newly diagnosed metastatic CRPC who are not currently receiving bone targeting agents.

Official Title
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Denosumab Plus Enzalutamide, Abiraterone and Prednisone Compared to Denosumab Plus Enzalutamide Alone for Men With Castrate Resistant Prostate Cancer (CRPC) With Bone Metastases: Clinical Testing and Feasibility of a Serum-based Metabolomics Profile

Conditions
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Prostate Cancer

Intervention / Treatment
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* Biological: Denosumab
* Drug: Enzalutamide
* Drug: Abiraterone
* Drug: Prednisone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologic proof of adenocarcinoma of the prostate with clinical evidence of metastatic disease to the bone. Castrate resistant progression of prostate carcinoma, as shown by: Serum testosterone level <50 ng/dL or prior bilateral orchiectomy. Treatment to maintain castrate levels of testosterone should continue, and Either symptomatic progression, or, if patient is asymptomatic then a rising serum PSA in two occasions at least 1 week apart, with minimum pre-treatment serum PSA of 5 ng/dL. Patients with nodal disease are eligible. Bi-dimensionally measurable disease within the bone. Life expectancy of at least 12 weeks. ECOG Performance status < 2 Adequate: Bone marrow function; absolute neutrophil count > 1,500 mm3, platelet count of > 100,000 mm3 and hemoglobin > 9.0 gm/dl. Hepatic function; SGOT/SGPT and conjugated bilirubin less than twice the upper limit of normal. Renal function; serum creatinine ≤ 2 mg/dL (or, if creatinine > 2 mg/dL, then a creatinine clearance of at least 35 ml/min (measured or estimated by the Cockroft formula: CLcr = [(140-age) x wt (kg)]/[72 x serum creatinine (mg/dL)]. No evidence of coagulopathy as indicated by PT < 1.5X upper limit of normal. Serum calcium (corrected) from 8 to11.5 mg/dL (2 to 2.9 mmol/L) - Patients must sign an informed consent indicating that they are aware of the investigational nature of the study. Exclusion Criteria: Patients with variant histologies (e.g., ductal or small cell carcinoma). Patients with visceral disease are ineligible. Patients who have had prior Sipuleucel-T, docetaxel, cabazitaxel, abiraterone or enzalutamide as a single agent, or in combination therapy. Concurrent cancer chemotherapy, radiotherapy or surgery. Concurrent serious infection. Life threatening illness (e.g., congestive heart failure, uncontrolled angina or myocardial infarction in the prior six months). Hypertension uncontrolled by medication. Patients who are known to require invasive dental procedures. No known or suspected brain metastases (NOTE: patients with treated epidural disease are allowed) Administration of any investigational drug within 28 days prior to receipt of denosumab. Age ≤ 18 years of age

Ages Eligible for Study
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Minimum Age: 18 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
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Alliance A031201<br>Denosumab plus enzalutamide, abiraterone and prednisone | Biological: Denosumab<br>* One 120 mg subcutaneous injection every four weeks. Protocol therapy will consist of 28-day cycles until no clinical benefit, confirmed disease progression or unacceptable toxicity.<br>Drug: Enzalutamide<br>* 160 mg enzalutamide by mouth daily<br>Drug: Abiraterone<br>* 1000 mg abiraterone by mouth daily<br>Drug: Prednisone<br>* 5 mg prednisone by mouth twice daily<br>|
| Active Comparator: Standard of Care<br>Denosumab plus enzalutamide alone | Biological: Denosumab<br>* One 120 mg subcutaneous injection every four weeks. Protocol therapy will consist of 28-day cycles until no clinical benefit, confirmed disease progression or unacceptable toxicity.<br>Drug: Enzalutamide<br>* 160 mg enzalutamide by mouth daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Measure Change in Serum-based Metabolites Associated With Bone Deposition, Growth and Turnover in Patients Who Have CRPC With Clinical Evidence of Metastatic Disease to the Bone, All Using Gas Chromatography-time-of-flight Mass Spectrometry (GC-TOFMS). |  | Prior to Registration, Registration, Day 1 of cycle 4 and 13 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Measure Time (Months) to Skeletal Related Event (SRE) of Patients on Therapy |  | Day 1 of each S.O.C cycle (28 days), and until confirmed radiographic disease progression AND initiation of other standard OR investigational agents for prostate cancer, up to 5 years post treatment | 
| Measure Time (Months) to Progression-free Survival of Patients on Therapy |  | Day 1 of each S.O.C cycle (28 days), and until confirmed radiographic disease progression AND initiation of other standard OR investigational agents for prostate cancer, up to 5 years post treatment | 
| Measure Time (Months) to Duration of Response of Patients on Therapy. |  | Day 1 of each S.O.C cycle (28 days), and until confirmed radiographic disease progression AND initiation of other standard OR investigational agents for prostate cancer, up to 5 years post treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Castrate-resistant prostate cancer with bone metastases