Denosumab Plus Enzalutamide, Abiraterone and Prednisone C... | NCT02758132

Status Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Alliance A031201	Active Comparator	Denosumab plus enzalutamide, abiraterone and prednisone	Biological: Denosumab Drug: Enzalutamide Drug: Abiraterone Drug: Prednisone
Standard of Care	Active Comparator	Denosumab plus enzalutamide alone	Biological: Denosumab Drug: Enzalutamide

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Denosumab	Biological	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.

Outcomes Module

Primary Outcomes

Measure	Description	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 Outcomes

Measure	Description	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

Other Outcomes

Measure	Description	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

Eligibility Module

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	Status	City	State	ZIP	Country	Contacts
University of Hawaii Cancer Center		Honolulu	Hawaii	96813	United States

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	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

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Arm/Group Information

ID	Title	Description
BG000	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
BG001	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
BG002	Total	Total of all reporting groups

Units	Counts
Participants	BG0000 BG0011 BG0021

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Categorical

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
<=18 years	BG0010 BG0020
Between 18 and 65 years	BG001

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG0010 BG0020
Male

Race (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
American Indian or Alaska Native	BG0010 BG0020
Asian

Region of Enrollment

Number

participants

Title

Denominators

Categories

United States

Title	Measurements
	BG0011 BG0021

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

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).

Patient expired before completing study

Posted

Prior to Registration, Registration, Day 1 of cycle 4 and 13

ID	Title	Description
OG000	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
OG001	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

Units	Counts
Participants	OG0000 OG0010

Secondary

Measure Time (Months) to Skeletal Related Event (SRE) of Patients on Therapy

Patient expired before completing study

Posted

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

ID	Title	Description
OG000	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
OG001	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

Units	Counts
Participants

Secondary

Measure Time (Months) to Progression-free Survival of Patients on Therapy

Patient expired before completing study

Posted

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

ID	Title	Description
OG000	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
OG001	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

Units	Counts
Participants

Secondary

Measure Time (Months) to Duration of Response of Patients on Therapy.

Patient expired before completing study

Posted

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

ID	Title	Description
OG000	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
OG001	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

Units	Counts
Participants

Other Pre-specified

Measure Change in Technetium Bone Scintigraphy on Therapy Via Technetium Bone Scintigraphy or Sodium Fluoride (NaF) PET/CT Imaging

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

Posted

Prior to Registration, Day 1 of cycle 4 and 13, Post-Treatment Follow-up (up to 5 years post treatment)

ID	Title	Description
OG000	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
OG001	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

Units	Counts
Participants

Other Pre-specified

Measure Change in Treatment Response Via RECIST Criteria

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

Posted

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

ID	Title	Description
OG000	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
OG001	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

Units	Counts
Participants

Other Pre-specified

Evaluate the Effect of Therapy on Quality of Life (QoL) in Patients Via QoL Questionnaire.

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

Posted

Prior to Registration, Registration, Day 1 of cycle 4 and 13

ID	Title	Description
OG000	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
OG001	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

Units	Counts
Participants

Other Pre-specified

Evaluate the Effect of Therapy on Narcotic Use in Patients on Therapy Via Case Report Forms.

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

Posted

Prior to Registration, Registration, Day 1 of cycle 4 and 13

ID	Title	Description
OG000	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
OG001	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

Units	Counts
Participants

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	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	0	0	0	0	0
EG001	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	1	1	1	0	0

ID	Term
D005834	Genital Neoplasms, Male
D014565	Urogenital Neoplasms
D009371	Neoplasms by Site
D009369	Neoplasms
D005832	Genital Diseases, Male
D000091662	Genital Diseases
D000091642	Urogenital Diseases
D011469	Prostatic Diseases
D052801	Male Urogenital Diseases

ID	Term
D061067	Antibodies, Monoclonal, Humanized
D000911	Antibodies, Monoclonal
D000906	Antibodies
D007136	Immunoglobulins
D007162	Immunoproteins
D001798	Blood Proteins
D011506	Proteins
D000602	Amino Acids, Peptides, and Proteins
D012712	Serum Globulins
D005916	Globulins
D011244	Pregnadienediols
D011245	Pregnadienes
D011278	Pregnanes
D013256	Steroids
D000072473	Fused-Ring Compounds
D011083	Polycyclic Compounds

ID	Term
D000069448	Denosumab
C540278	enzalutamide
C089740	abiraterone
D011241	Prednisone