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

NCT02758132 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: Rosser 2015-1
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

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.

Conditions

Prostate Cancer

Keywords

Castrate-resistant prostate cancer with bone metastases

Outcome Measures

Primary Outcomes (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 Outcomes (3)

• 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 Outcomes (4)

• 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

Study Arms (2)

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

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.

Alliance A031201; Standard of Care

Enzalutamide DRUG

160 mg enzalutamide by mouth daily

Alliance A031201; Standard of Care

Abiraterone DRUG

1000 mg abiraterone by mouth daily

Alliance A031201

Prednisone DRUG

5 mg prednisone by mouth twice daily

Alliance A031201

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Hawaii: lead

Study Sites (1)

University of Hawaii Cancer Center

Honolulu, Hawaii, 96813, United States

Location

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

Denosumab; enzalutamide; abiraterone; Prednisone

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Limitations and 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.

Results Point of Contact

• Title: Stacy Mercado
• Organization: University of Hawaii Cancer Center

smercado@cc.hawaii.edu

8084404561

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 11, 2016
• First Posted: May 2, 2016
• Study Start: March 1, 2016
• Primary Completion: September 6, 2016
• Study Completion: September 6, 2016
• Last Updated: November 8, 2019
• Results First Posted: October 2, 2019

Record last verified: 2019-11

Locations

US (1)