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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

Primary Purpose

Prostate Cancer

Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Denosumab
Enzalutamide
Abiraterone
Prednisone
Sponsored by
University of Hawaii
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Prostate Cancer focused on measuring Castrate-resistant prostate cancer with bone metastases

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)MaleDoes not accept healthy volunteers

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

Sites / Locations

  • University of Hawaii Cancer Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Active Comparator

Arm Label

Alliance A031201

Standard of Care

Arm Description

Denosumab plus enzalutamide, abiraterone and prednisone

Denosumab plus enzalutamide alone

Outcomes

Primary Outcome Measures

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).

Secondary Outcome Measures

Measure Time (Months) to Skeletal Related Event (SRE) of Patients on Therapy
Measure Time (Months) to Progression-free Survival of Patients on Therapy
Measure Time (Months) to Duration of Response of Patients on Therapy.

Full Information

First Posted
April 11, 2016
Last Updated
November 6, 2019
Sponsor
University of Hawaii
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1. Study Identification

Unique Protocol Identification Number
NCT02758132
Brief Title
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

2. Study Status

Record Verification Date
November 2019
Overall Recruitment Status
Terminated
Why Stopped
Low accruals
Study Start Date
March 1, 2016 (Actual)
Primary Completion Date
September 6, 2016 (Actual)
Study Completion Date
September 6, 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Hawaii

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Prostate Cancer
Keywords
Castrate-resistant prostate cancer with bone metastases

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
1 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Alliance A031201
Arm Type
Active Comparator
Arm Description
Denosumab plus enzalutamide, abiraterone and prednisone
Arm Title
Standard of Care
Arm Type
Active Comparator
Arm Description
Denosumab plus enzalutamide alone
Intervention Type
Biological
Intervention Name(s)
Denosumab
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.
Intervention Type
Drug
Intervention Name(s)
Enzalutamide
Intervention Description
160 mg enzalutamide by mouth daily
Intervention Type
Drug
Intervention Name(s)
Abiraterone
Intervention Description
1000 mg abiraterone by mouth daily
Intervention Type
Drug
Intervention Name(s)
Prednisone
Intervention Description
5 mg prednisone by mouth twice daily
Primary Outcome Measure Information:
Title
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
Secondary Outcome Measure Information:
Title
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
Title
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
Title
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
Other Pre-specified Outcome Measures:
Title
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)
Title
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
Title
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
Title
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

10. Eligibility

Sex
Male
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Facility Information:
Facility Name
University of Hawaii Cancer Center
City
Honolulu
State/Province
Hawaii
ZIP/Postal Code
96813
Country
United States

12. IPD Sharing Statement

Learn more about this trial

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

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