Denosumab Plus Enzalutamide, Abiraterone and Prednisone Compared to Denosumab Plus Enzalutamide Alone for Men With Castrate Resistant Prostate Cancer (CRPC) With Bone Metastases
Condition: Prostate Cancer
MeSH terms: Prostatic Neoplasms; Neoplasm Metastasis
Intervention: Denosumab; Enzalutamide; Abiraterone; Prednisone
Intervention description: 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.; 160 mg enzalutamide by mouth daily; 1000 mg abiraterone by mouth daily; 5 mg prednisone by mouth twice daily
Intervention MeSH terms: Denosumab; Prednisone
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 1.0
Sex: Male
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Castrate-resistant prostate cancer with bone metastases

Summary:

      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.
    

Eligibility criteria:

        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