Prostate Cancer
Conditions
Keywords
Castrate-resistant prostate cancer with bone metastases
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.
Interventions
BIOLOGICALDenosumab
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.
DRUGEnzalutamide
160 mg enzalutamide by mouth daily
DRUGAbiraterone
1000 mg abiraterone by mouth daily
DRUGPrednisone
5 mg prednisone by mouth twice daily
Sponsors
University of Hawaii
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | 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
| Measure | 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 |
Other
| Measure | Time frame |
|---|---|
| Measure Change in Technetium Bone Scintigraphy on Therapy Via Technetium Bone Scintigraphy or Sodium Fluoride (NaF) PET/CT Imaging | Prior to Registration, Day 1 of cycle 4 and 13, Post-Treatment Follow-up (up to 5 years post treatment) |
| Measure Change in Treatment Response Via RECIST Criteria | 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 |
| Evaluate the Effect of Therapy on Quality of Life (QoL) in Patients Via QoL Questionnaire. | Prior to Registration, Registration, Day 1 of cycle 4 and 13 |
| Evaluate the Effect of Therapy on Narcotic Use in Patients on Therapy Via Case Report Forms. | Prior to Registration, Registration, Day 1 of cycle 4 and 13 |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Alliance A031201 Denosumab plus enzalutamide, abiraterone and prednisone
Denosumab: 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.
Enzalutamide: 160 mg enzalutamide by mouth daily
Abiraterone: 1000 mg abiraterone by mouth daily
Prednisone: 5 mg prednisone by mouth twice daily | 0 |
| Standard of Care Denosumab plus enzalutamide alone
Denosumab: 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.
Enzalutamide: 160 mg enzalutamide by mouth daily | 1 |
| Total | 1 |
Baseline characteristics
| Characteristic | Standard of Care | Total |
|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 1 Participants | 1 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants |
| Region of Enrollment United States | 1 participants | 1 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 1 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 0 | 1 / 1 |
| other Total, other adverse events | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 0 / 0 | 1 / 1 |
Outcome results
Primary
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).
Time frame: Prior to Registration, Registration, Day 1 of cycle 4 and 13
Population: Patient expired before completing study
Secondary
Measure Time (Months) to Duration of Response of Patients on Therapy.
Time frame: 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
Population: Patient expired before completing study
Secondary
Measure Time (Months) to Progression-free Survival of Patients on Therapy
Time frame: 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
Population: Patient expired before completing study
Secondary
Measure Time (Months) to Skeletal Related Event (SRE) of Patients on Therapy
Time frame: 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
Population: Patient expired before completing study
Other Pre-specified
Evaluate the Effect of Therapy on Narcotic Use in Patients on Therapy Via Case Report Forms.
Time frame: Prior to Registration, Registration, Day 1 of cycle 4 and 13
Population: one subject enrolled and they discontinued early from trial, no analysis conducted
Other Pre-specified
Evaluate the Effect of Therapy on Quality of Life (QoL) in Patients Via QoL Questionnaire.
Time frame: Prior to Registration, Registration, Day 1 of cycle 4 and 13
Population: one subject enrolled and they discontinued early from trial, no analysis conducted
Other Pre-specified
Measure Change in Technetium Bone Scintigraphy on Therapy Via Technetium Bone Scintigraphy or Sodium Fluoride (NaF) PET/CT Imaging
Time frame: Prior to Registration, Day 1 of cycle 4 and 13, Post-Treatment Follow-up (up to 5 years post treatment)
Population: one subject enrolled and they discontinued early from trial, no analysis conducted
Other Pre-specified
Measure Change in Treatment Response Via RECIST Criteria
Time frame: 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
Population: one subject enrolled and they discontinued early from trial, no analysis conducted