Clinical trial NCT02758132: Denosumab Plus Enzalutamide, Abiraterone and Prednisone Compared to Denosumab Plus Enzalutamide Alone for Men With Castrate Resistant Prostate Cancer (CRPC) With Bone Metastases
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Prostate Cancer
Keywords: Castrate-resistant prostate cancer with bone metastases
Lead sponsor: University of Hawaii
Sponsor class: OTHER
First posted: 2016-05-02
Enrollment: 1
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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

Primary outcomes:
measure: 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).
timeFrame: Prior to Registration, Registration, Day 1 of cycle 4 and 13
Secondary outcomes:
measure: Measure Time (Months) to Skeletal Related Event (SRE) of Patients on Therapy
timeFrame: 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: Measure Time (Months) to Progression-free Survival of Patients on Therapy
timeFrame: 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: Measure Time (Months) to Duration of Response of Patients on Therapy.
timeFrame: 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
Other outcomes:
measure: Measure Change in Technetium Bone Scintigraphy on Therapy Via Technetium Bone Scintigraphy or Sodium Fluoride (NaF) PET/CT Imaging
timeFrame: Prior to Registration, Day 1 of cycle 4 and 13, Post-Treatment Follow-up (up to 5 years post treatment)
measure: Measure Change in Treatment Response Via RECIST Criteria
timeFrame: 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: Evaluate the Effect of Therapy on Quality of Life (QoL) in Patients Via QoL Questionnaire.
timeFrame: Prior to Registration, Registration, Day 1 of cycle 4 and 13
measure: Evaluate the Effect of Therapy on Narcotic Use in Patients on Therapy Via Case Report Forms.
timeFrame: Prior to Registration, Registration, Day 1 of cycle 4 and 13
Locations:
city: Honolulu
country: United States
facility: University of Hawaii Cancer Center
state: Hawaii
Study officials:
References: