NCT01949337|UnknownPhase 3ResultsDMC

Enzalutamide With or Without Abiraterone and Prednisone in Treating Patients With Castration-Resistant Metastatic Prostate Cancer

Phase III Trial of Enzalutamide (NSC# 766085) Versus Enzalutamide, Abiraterone and Prednisone for Castration Resistant Metastatic Prostate Cancer

Alliance for Clinical Trials in Oncology ClinicalTrials.gov

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3 other identifiers

A031201U10CA031946NCI-2013-01737

Study Type

interventional

Target

1,311

Locations

3 countries

Sites

539

Timeline

RegisteredSep 2013

StartedJan 2014

CompletionAug 2024

Brief Summary

This randomized phase III trial studies enzalutamide to see how well it works compared to enzalutamide, abiraterone, and prednisone in treating patients with castration-resistant metastatic prostate cancer. Androgens can cause the growth of prostate cancer cells. Drugs, such as enzalutamide, abiraterone acetate, and prednisone, may lessen the amount of androgens made by the body.

Trial Health

At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date

Enrollment

1,311

participants targeted

Target at P75+ for phase_3

Timeline

Completed

Started Jan 2014

Longer than P75 for phase_3

Geographic Reach

3 countries

539 active sites

Status

unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

10.6 years study duration

First Submitted

Initial submission to the registry

September 20, 2013

Completed

4 days until next milestone

First Posted

Study publicly available on registry

September 24, 2013

Completed

4 months until next milestone

Study Start

First participant enrolled

January 22, 2014

Completed

4.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

November 2, 2018

Completed

1.6 years until next milestone

Results Posted

Study results publicly available

June 1, 2020

Completed

4.3 years until next milestone

Study Completion

Last participant's last visit for all outcomes

August 31, 2024

Completed

Last Updated

September 28, 2023

Status Verified

September 1, 2023

Enrollment Period

4.8 years

First QC Date

September 20, 2013

Results QC Date

May 14, 2020

Last Update Submit

September 13, 2023

Conditions

Adenocarcinoma of the Prostate Hormone-resistant Prostate Cancer Recurrent Prostate Cancer Stage IV Prostate Cancer

Outcome Measures

Primary Outcomes (1)

Overall Survival (OS)
Overall survival is defined as the time from study registration to death due to any cause.
Up to 5 years post treatment

Secondary Outcomes (6)

Number of Participants Who Has Experienced at Least One Toxicity (Defined as a Grade 3 or Higher Adverse Event Deemed at Least Possibly Related to Treatment)
Up to 5 years post treatment
Decline in Prostate Specific Antigen (PSA)
Up to 5 years post treatment
Progression Free Survival (PFS)
Up to 5 years post treatment
Objective Response Rate
Up to 5 years post treatment
Radiographic Progression Free Survival (rPFS)
Up to 5 years post treatment
+1 more secondary outcomes

Study Arms (2)

Arm A: (enzalutamide)

EXPERIMENTAL

Patients receive enzalutamide 160 mg PO QD. Treatment will continue until confirmed disease progression or unacceptable toxicity.

Drug: enzalutamide

Arm B: (enzalutamide, abiraterone, prednisone)

EXPERIMENTAL

Patients receive enzalutamide 160 mg PO QD, abiraterone 1000 mg PO QD, and prednisone 5 mg PO BID. Treatment will continue until confirmed disease progression or unacceptable toxicity.

Drug: enzalutamideDrug: abirateroneDrug: prednisone

Interventions

enzalutamideDRUG

Enzalutamide 160 mg daily, orally

Arm A: (enzalutamide)Arm B: (enzalutamide, abiraterone, prednisone)

abirateroneDRUG

abiraterone 1000 mg daily, orally

Arm B: (enzalutamide, abiraterone, prednisone)

prednisoneDRUG

prednisone 5 mg twice daily, orally

Arm B: (enzalutamide, abiraterone, prednisone)

Eligibility Criteria

Age18 Years+

Sexmale

Healthy VolunteersNo

Age GroupsAdult (18-64), Older Adult (65+)

Eligibility Criteria: 1. Documentation of Disease - Progressive castration-resistant metastatic prostate cancer with histologically or cytologically confirmed adenocarcinoma of the prostate without neuroendocrine differentiation or small cell features 2. Patients must have measurable or non-measurable disease: 1. Measurable Disease - For visceral or extra nodal lesions to be considered measurable, they must be ≥ 10 mm in one dimension, using spiral CT. For lymph nodes to be considered measurable (ie, target or evaluable lesions), they must be ≥ 20 mm in at least one dimension, using spiral CT. 2. Non-Measurable Disease - All other lesions, including small lesions (longest diameter \< 20 mm with conventional techniques or \< 10 mm with spiral CT scan) and truly non-measurable lesions. Lesions that are considered non-measurable include bone lesions (only). 3. Patients with node only disease (ie, no presence of visceral, extra nodal lesions or bone lesions) must have node(s) that measure ≥ 15 mm in short axis. 3. Progressive Disease - Patients must have progressive disease at study entry defined as one or more of the following three criteria that occurred while the patient was on androgen deprivation therapy. For patients enrolling on the basis of soft tissue or bone progression, the baseline scan must show progression relative to a comparison scan. If the comparison scan is not available, the baseline scan report must reference the previous scan to document progression. 1. PSA progression defined by a minimum of two rising PSA levels with an interval of ≥ 1 week between each determination. Patients who received an anti-androgen must have progression documented by a minimum of two rising PSA levels with an interval of ≥ 1 week between each determination such that at least the second of these rises is ≥ 4 weeks since last flutamide, bicalutamide or nilutamide. The PSA value at the screening should be ≥ 2 µg/L (2 ng/mL) . 2. Soft tissue disease progression defined by the protocol 3. Bone disease progression defined by the Prostate Cancer Working Group 2 (PCWG2) with two or more new lesions on bone scan 4. Prior Treatment 1. No treatment with prior taxane-based chemotherapy for metastatic disease * Patients who received prior taxane-based chemotherapy as neoadjuvant or adjuvant therapy for local disease, or who received taxane-based therapy in the PSA clinical (non-metastatic) state is allowable provided that the total duration of exposure was six cycles or less and chemotherapy was completed more than 6 months prior to registration * Taxane-based chemotherapy that was aborted due to allergic reactions or intolerance to chemotherapy and therefore received one cycle of prior therapy is allowable 2. No prior enzalutamide, abiraterone or other novel antiandrogen or androgen synthesis inhibitor 3. No treatment with any of the following for prostate cancer within 4 weeks prior to enrollment: * Hormonal therapy (e.g., androgen receptor \[AR\] antagonists, 5 alpha reductase inhibitors, estrogens) Note: Treatment with bicalutamide and nilutamide within 4 weeks prior to enrollment is not allowed. Treatment with flutamide within 4 weeks prior to enrollment is not allowed. Treatment with all other gonadotropin- releasing hormone (GnRH) analogues or antagonists is allowed. * Chemotherapy * Biologic therapy * Investigational therapy * Immunotherapy 4. No use of herbal products that may decrease PSA levels within 4 weeks prior to enrollment 5. No use of systemic steroids greater than the equivalent of 10 mg of prednisone/prednisolone per day within 4 weeks prior to enrollment 6. No prior use of ketoconazole for greater than 7 days 7. No prior radiation therapy or radionuclide therapy for the treatment of metastasis within four weeks prior to enrollment 8. Patients receiving bisphosphonate therapy or denosumab must have been on a stable dose for at least 4 weeks prior to enrollment 9. Patients must maintain ongoing androgen deprivation therapy with a GnRH analogue, antagonist, or bilateral orchiectomy (i.e., surgical or medical castration) 5. Patient History 1. No known or suspected brain metastases (NOTE: patients with treated epidural disease are allowed) 2. No planned palliative procedures for alleviation of bone pain such as radiation therapy or surgery 3. No structurally unstable bone lesions suggesting impending fracture 4. No history of seizure or any condition that may increase the patient's seizure risk (e.g., prior cortical stroke, significant brain trauma). No history of transient ischemic attack (TIA) within 12 months of enrollment 5. No clinically significant cardiovascular disease including: * Myocardial infarction (MI) within 6 months * Uncontrolled angina within 3 months * Congestive heart failure (CHF) with New York Heart Association (NYHA) class 3 or 4, or patients with NYHA class 3 or 4 in the past, unless a screening echocardiogram (echo) or multigated acquisition scan (MUGA) performed within three months demonstrates an ejection fraction (EF) \> 45% * History of clinically significant ventricular arrhythmias (e.g., ventricular tachycardia, ventricular fibrillation, torsades de pointes) * History of Mobitz II second degree or third degree heart block without a permanent pacemaker in place * Hypotension (systolic blood pressure \[BP\] \< 86 mmHg) or bradycardia (\< 50 bpm) at screening * Uncontrolled hypertension (systolic BP \> 170 mmHg or diastolic BP \> 105 mmHg at screening) 6. No gastrointestinal (GI) disorder that negatively affects absorption 7. No major surgery within 4 weeks prior to enrollment 6. Age and performance status 1. Age ≥ 18 years of age 2. Eastern Cooperative Oncology Group (ECOG) performance status 0-1 3. Asymptomatic or mildly symptomatic from prostate cancer 7. Required Initial Laboratory Values 1. Granulocytes ≥ 1,500/µL 2. Platelet count ≥ 100,000/µL 3. Hemoglobin ≥ 9 g/dL 4. Creatinine ≤ 2 x upper limits of normal (ULN) 5. Bilirubin ≤ 1.5 x ULN 6. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≤ 2 x ULN 7. Albumin ≥ 3 g/dl 8. Total testosterone ≤ 50 ng/dL (1.7 nmol/L)

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

Alliance for Clinical Trials in Oncologylead
National Cancer Institute (NCI)collaborator
Astellas Pharma US, Inc.collaborator
Medivation, Inc.collaborator
Biologics, Inc.collaborator

Study Sites (539)

University of Alabama at Birmingham Cancer Center

Birmingham, Alabama, 35233, United States

Location

Southern Cancer Center PC-Providence

Mobile, Alabama, 36608, United States

Location

Katmai Oncology Group

Anchorage, Alaska, 99508, United States

Location

Providence Alaska Medical Center

Anchorage, Alaska, 99508, United States

Location

Mayo Clinic in Arizona

Scottsdale, Arizona, 85259, United States

Location

University of Arizona Cancer Center-Orange Grove Campus

Tucson, Arizona, 85704, United States

Location

University of Arizona Cancer Center-North Campus

Tucson, Arizona, 85719, United States

Location

The University of Arizona Medical Center-University Campus

Tucson, Arizona, 85724, United States

Location

Fowler Family Center for Cancer Care

Jonesboro, Arkansas, 72401, United States

Location

University of Arkansas for Medical Sciences

Little Rock, Arkansas, 72205, United States

Location

Veteran's Administration Medical Center

Little Rock, Arkansas, 72205, United States

Location

Kaiser Permanente-Anaheim

Anaheim, California, 92807, United States

Location

Kaiser Permanente-Deer Valley Medical Center

Antioch, California, 94531, United States

Location

Kaiser Permanente-Baldwin Park

Baldwin Park, California, 91706, United States

Location

Kaiser Permanente-Bellflower

Bellflower, California, 90706, United States

Location

Alta Bates Summit Medical Center-Herrick Campus

Berkeley, California, 94704, United States

Location

Providence Saint Joseph Medical Center/Disney Family Cancer Center

Burbank, California, 91505, United States

Location

City of Hope Comprehensive Cancer Center

Duarte, California, 91010, United States

Location

Kaiser Permanente Hospital

Fontana, California, 92335, United States

Location

Kaiser Permanente-Fremont

Fremont, California, 94538, United States

Location

University Oncology Associates

Fresno, California, 93701, United States

Location

California Cancer Center - North Fresno

Fresno, California, 93720, United States

Location

Kaiser Permanente

Fresno, California, 93720, United States

Location

Marin Cancer Care Inc

Greenbrae, California, 94904, United States

Location

Kaiser Permanente - Harbor City

Harbor City, California, 90710, United States

Location

Kaiser Permanente-Irvine

Irvine, California, 92618, United States

Location

UC San Diego Moores Cancer Center

La Jolla, California, 92093, United States

Location

Loma Linda University Medical Center

Loma Linda, California, 92354, United States

Location

Kaiser Permanente Los Angeles Medical Center

Los Angeles, California, 90027, United States

Location

Los Angeles County-USC Medical Center

Los Angeles, California, 90033, United States

Location

USC / Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

Location

Kaiser Permanente-Cadillac

Los Angeles, California, 90034, United States

Location

Fremont - Rideout Cancer Center

Marysville, California, 95901, United States

Location

Memorial Medical Center

Modesto, California, 95355, United States

Location

Kaiser Permanente-Modesto

Modesto, California, 95356, United States

Location

USC Norris Oncology/Hematology-Newport Beach

Newport Beach, California, 92663, United States

Location

Kaiser Permanente-Oakland

Oakland, California, 94611, United States

Location

UC Irvine Health/Chao Family Comprehensive Cancer Center

Orange, California, 92868, United States

Location

Palo Alto Medical Foundation Health Care

Palo Alto, California, 94301, United States

Location

Kaiser Permanente - Panorama City

Panorama City, California, 91402, United States

Location

Feather River Cancer Center

Paradise, California, 95969, United States

Location

Kaiser Permanente-Redwood City

Redwood City, California, 94063, United States

Location

Kaiser Permanente-Richmond

Richmond, California, 94801, United States

Location

Kaiser Permanente-Riverside

Riverside, California, 92505, United States

Location

Kaiser Permanente-Roseville

Roseville, California, 95661, United States

Location

University of California Davis Comprehensive Cancer Center

Sacramento, California, 95817, United States

Location

Kaiser Permanente-South Sacramento

Sacramento, California, 95823, United States

Location

Kaiser Permanente - Sacramento

Sacramento, California, 95825, United States

Location

Kaiser Permanente-San Diego Zion

San Diego, California, 92120, United States

Location

Sharp Memorial Hospital

San Diego, California, 92123, United States

Location

Naval Medical Center -San Diego

San Diego, California, 92134, United States

Location

Veterans Administration-San Diego Medical Center

San Diego, California, 92161, United States

Location

Kaiser Permanente-San Francisco

San Francisco, California, 94115, United States

Location

UCSF Medical Center-Mount Zion

San Francisco, California, 94115, United States

Location

Veterans Affairs Medical Center - San Francisco

San Francisco, California, 94121, United States

Location

UCSF Medical Center-Mission Bay

San Francisco, California, 94158, United States

Location

Kaiser Permanente-Santa Teresa-San Jose

San Jose, California, 95119, United States

Location

Kaiser Permanente San Leandro

San Leandro, California, 94577, United States

Location

Kaiser Permanente-San Marcos

San Marcos, California, 92069, United States

Location

Kaiser Permanente-San Rafael

San Rafael, California, 94903, United States

Location

Kaiser Permanente Medical Center - Santa Clara

Santa Clara, California, 95051, United States

Location

Palo Alto Medical Foundation-Santa Cruz

Santa Cruz, California, 95065, United States

Location

Kaiser Permanente-Santa Rosa

Santa Rosa, California, 95403, United States

Location

Kaiser Permanente-South San Francisco

South San Francisco, California, 94080, United States

Location

Saint Helena Hospital

St. Helena, California, 94574, United States

Location

Saint Joseph's Medical Center

Stockton, California, 95204, United States

Location

Kaiser Permanente-Stockton

Stockton, California, 95210, United States

Location

Palo Alto Medical Foundation-Sunnyvale

Sunnyvale, California, 94086, United States

Location

Kaiser Permanente Medical Center-Vacaville

Vacaville, California, 95688, United States

Location

Kaiser Permanente-Vallejo

Vallejo, California, 94589, United States

Location

Kaiser Permanente-Walnut Creek

Walnut Creek, California, 94596, United States

Location

Kaiser Permanente

Woodland Hills, California, 91367, United States

Location

Rocky Mountain Cancer Centers-Boulder

Boulder, Colorado, 80304, United States

Location

Memorial Hospital Colorado Springs

Colorado Springs, Colorado, 80909, United States

Location

Kaiser Permanente-Franklin

Denver, Colorado, 80205, United States

Location

Southwest Oncology PC

Durango, Colorado, 81301, United States

Location

The Shaw Regional Cancer Center

Edwards, Colorado, 81632, United States

Location

Poudre Valley Hospital

Fort Collins, Colorado, 80524, United States

Location

Rocky Mountain Cancer Centers-Lakewood

Lakewood, Colorado, 80228, United States

Location

Greenwich Hospital

Greenwich, Connecticut, 06830, United States

Location

Smilow Cancer Hospital Care Center at Saint Francis

Hartford, Connecticut, 06105, United States

Location

Middlesex Hospital

Middletown, Connecticut, 06457, United States

Location

Norwalk Hospital

Norwalk, Connecticut, 06856, United States

Location

Eastern Connecticut Hematology and Oncology Associates

Norwich, Connecticut, 06360, United States

Location

Stamford Hospital/Bennett Cancer Center

Stamford, Connecticut, 06904, United States

Location

Veterans Affairs Connecticut Healthcare System-West Haven Campus

West Haven, Connecticut, 06516, United States

Location

Medical Oncology Hematology Consultants PA

Newark, Delaware, 19713, United States

Location

MedStar Georgetown University Hospital

Washington D.C., District of Columbia, 20007, United States

Location

Sibley Memorial Hospital

Washington D.C., District of Columbia, 20016, United States

Location

Veterans Affairs Medical Center -Washington DC

Washington D.C., District of Columbia, 20422, United States

Location

Baptist MD Anderson Cancer Center

Jacksonville, Florida, 32207, United States

Location

Lakeland Regional Cancer Center

Lakeland, Florida, 33805, United States

Location

Mount Sinai Medical Center

Miami Beach, Florida, 33140, United States

Location

Florida Hospital Orlando

Orlando, Florida, 32803, United States

Location

UF Cancer Center at Orlando Health

Orlando, Florida, 32806, United States

Location

Sacred Heart Hospital

Pensacola, Florida, 32504, United States

Location

Northside Hospital

Atlanta, Georgia, 30342, United States

Location

John B Amos Cancer Center

Columbus, Georgia, 31904, United States

Location

Atlanta VA Medical Center

Decatur, Georgia, 30033, United States

Location

Medical Center of Central Georgia

Macon, Georgia, 31201, United States

Location

Lewis Cancer and Research Pavilion at Saint Joseph's/Candler

Savannah, Georgia, 31405, United States

Location

South Georgia Medical Center/Pearlman Cancer Center

Valdosta, Georgia, 31602, United States

Location

Hawaii Cancer Care Inc-POB II