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

• Sponsor: University of Hawaii (Other)
• Overall Status: Terminated
• CT.gov ID: NCT02758132
• Collaborator: (none)
• Enrollment: 1
• Location: 1
• Arms: 2
• Actual Duration (Months): 6.2
• Patients Per Site Per Month: 0.2

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Prostate Cancer	Biological: Denosumab; Drug: Enzalutamide; Drug: Abiraterone; Drug: Prednisone	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 1 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: Mar 1, 2016
• Actual Primary Completion Date: Sep 6, 2016
• Actual Study Completion Date: Sep 6, 2016

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Alliance A031201 Denosumab plus enzalutamide, abiraterone and prednisone	Biological: 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.; Drug: Enzalutamide; 160 mg enzalutamide by mouth daily; Drug: Abiraterone; 1000 mg abiraterone by mouth daily; Drug: Prednisone; 5 mg prednisone by mouth twice daily
Active Comparator: Standard of Care Denosumab plus enzalutamide alone	Biological: 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.; Drug: Enzalutamide; 160 mg enzalutamide by mouth daily

Outcome Measures

Primary Outcome Measures

1. 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

1. 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]

2. 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]

3. 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 Outcome Measures

1. 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)]

2. 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]

3. 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]

4. 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]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Male
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Hawaii Cancer Center	Honolulu	Hawaii	United States	96813

Sponsors and Collaborators

• University of Hawaii

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: University of Hawaii
• ClinicalTrials.gov Identifier: NCT02758132
• Other Study ID Numbers: Rosser 2015-1
• First Posted: May 2, 2016
• Last Update Posted: Nov 8, 2019
• Last Verified: Nov 1, 2019

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by University of Hawaii: Castrate-resistant prostate cancer with bone metastases
• Additional relevant MeSH terms: Prostatic Neoplasms; Neoplasm Metastasis; Denosumab; Prednisone

Study Results

Participant Flow

Arm/Group Title	Alliance A031201	Standard of Care
Arm/Group Description	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	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
Period Title: Overall Study
STARTED	0	1
COMPLETED	0	0
NOT COMPLETED	0	1

Baseline Characteristics

Arm/Group Title	Alliance A031201	Standard of Care	Total
Arm/Group Description	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	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	Total of all reporting groups
Overall Participants	0	1	1
Age (Count of Participants)
<=18 years	0 NaN	0 0%
Between 18 and 65 years	0 NaN	0 0%
>=65 years	1 Infinity	1 100%
Sex: Female, Male (Count of Participants)
Female	0 NaN	0 0%
Male	1 Infinity	1 100%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 NaN	0 0%
Asian	0 NaN	0 0%
Native Hawaiian or Other Pacific Islander	0 NaN	0 0%
Black or African American	0 NaN	0 0%
White	0 NaN	0 0%
More than one race	0 NaN	0 0%
Unknown or Not Reported	1 Infinity	1 100%
Region of Enrollment (participants) [Number]
United States	1 Infinity	1 100%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

Patient expired before completing study

Arm/Group Title	Alliance A031201	Standard of Care
Arm/Group Description	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	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
Measure Participants	0	0

2. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Patient expired before completing study

Arm/Group Title	Alliance A031201	Standard of Care
Arm/Group Description	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	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
Measure Participants	0	0

3. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Patient expired before completing study

Arm/Group Title	Alliance A031201	Standard of Care
Arm/Group Description	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	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
Measure Participants	0	0

4. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Patient expired before completing study

Arm/Group Title	Alliance A031201	Standard of Care
Arm/Group Description	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	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
Measure Participants	0	0

5. Other Pre-specified Outcome

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)

Outcome Measure Data

Analysis Population Description

one subject enrolled and they discontinued early from trial, no analysis conducted

Arm/Group Title	Alliance A031201	Standard of Care
Arm/Group Description	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	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
Measure Participants	0	0

6. Other Pre-specified Outcome

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

Outcome Measure Data

Analysis Population Description

one subject enrolled and they discontinued early from trial, no analysis conducted

Arm/Group Title	Alliance A031201	Standard of Care
Arm/Group Description	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	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
Measure Participants	0	0

7. Other Pre-specified Outcome

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

Outcome Measure Data

Analysis Population Description

one subject enrolled and they discontinued early from trial, no analysis conducted

Arm/Group Title	Alliance A031201	Standard of Care
Arm/Group Description	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	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
Measure Participants	0	0

8. Other Pre-specified Outcome

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

Outcome Measure Data

Analysis Population Description

one subject enrolled and they discontinued early from trial, no analysis conducted

Arm/Group Title	Alliance A031201	Standard of Care
Arm/Group Description	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	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
Measure Participants	0	0

Adverse Events

Time Frame	Adverse events were captured over 6 months
Adverse Event Reporting Description	adverse event collection performed by standard collection practices, medical chart review, disclosure from subject
Arm/Group Title	Alliance A031201		Standard of Care
Arm/Group Description	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		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
All Cause Mortality
	Alliance A031201		Standard of Care
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		1/1 (100%)
Serious Adverse Events
	Alliance A031201		Standard of Care
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		1/1 (100%)
Nervous system disorders
intracranial hemorrhage	0/0 (NaN)	0	1/1 (100%)	1
Other (Not Including Serious) Adverse Events
	Alliance A031201		Standard of Care
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		0/0 (NaN)

Limitations/Caveats

Trial was terminated early due to low accrual of one subject. Data analysis not conducted due to the one enrolled subject not receiving all the treatment.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.