A Phase III Study of Cabazitaxel With or Without Carboplatin in Patients With Metastatic Castrate-Resistant Prostate Cancer (mCRPC), Stratified by Aggressive Variant Signature
Summary
This phase III trial compares the effect of adding carboplatin to the standard of care chemotherapy drug cabazitaxel versus cabazitaxel alone in treating prostate cancer that keeps growing even when the amount of testosterone in the body is reduced to very low levels (castrate-resistant) and that has spread from where it first started (primary site) to other places in the body (metastatic). Carboplatin is in a class of medications known as platinum-containing compounds. Carboplatin works by killing, stopping or slowing the growth of tumor cells. Chemotherapy drugs, such as cabazitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Prednisone is often given together with chemotherapy drugs. Prednisone is in a class of medications called corticosteroids. It is used to reduce inflammation and lower the body's immune response to help lessen the side effects of chemotherapy drugs and to help the chemotherapy work. Giving carboplatin with the standard of care chemotherapy drug cabazitaxel may be better at treating metastatic castrate-resistant prostate cancer.
Detailed description
PRIMARY OBJECTIVES: I. To compare radiographic progression free survival (rPFS) between the two treatment arms in the subset of aggressive variant prostate cancer - molecular-pathologic signature (AVPC-MS)-positive participants. II. If the AVPC-MS positive test is statistically significant, test in AVPC-MS negative participants whether the combination of carboplatin and cabazitaxel improves rPFS. SECONDARY OBJECTIVES: I. To compare overall survival (OS) between the two treatment arms, stratified by AVPC-MS positive versus (vs.) negative. II. To compare response rates for prostate specific antigen (PSA), total alkaline phosphatase, and Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 between the two treatment arms, stratified by AVPC-MS positive vs. negative. III. To compare rPFS between the two treatment arms for the full trial. IV. To compare rPFS between the two treatment arms for the AVPC-MS negative group in the absence of a positive treatment effect in the AVPC-MS positive group. V. To compare progression free survival (PFS) between the two treatment arms, stratified by AVPC-MS positive vs. negative. VI. To compare toxicities between the two arms in participants who receive any treatment on study. BANKING OBJECTIVES: I. To bank specimens for future correlative studies. OUTLINE: Patients are randomized to 1 of 2 arms. ARM 1: Patients receive cabazitaxel intravenously (IV) over 60 minutes on day 1 of each cycle and prednisone orally (PO) twice daily (BID) on days 1-21 of each cycle. Cycles repeat every 21 days for up to 10 cycles in the absence of disease progression or unacceptable toxicity. ARM 2: Patients receive cabazitaxel and carboplatin IV over 60 minutes on day 1 of each cycle and prednisone PO BID on days 1-21 of each cycle. Cycles repeat every 21 days for up to 10 cycles in the absence of disease progression or unacceptable toxicity. All patients undergo blood sample collection, bone scan, computed tomography (CT), positron emission tomography (PET), or magnetic resonance imaging (MRI) throughout the trial and chest radiography (x-ray) before randomization. After completion of study treatment, patients are followed every 12 weeks for 1 year after randomization, and then every 26 weeks for up to 4 years after randomization or until death, whichever occurs first.
Arms & interventions
- ProcedureBiospecimen Collection
Undergo blood sample collection
- ProcedureBone Scan
Undergo bone scan
- DrugCabazitaxel
Given IV
- DrugCarboplatin
Given IV
- ProcedureChest Radiography
Undergo chest x-ray
- ProcedureComputed Tomography
Undergo CT or PET/CT
- ProcedureMagnetic Resonance Imaging
Undergo MRI
- ProcedurePositron Emission Tomography
Undergo PET/CT
- DrugPrednisone
Given PO
Outcome measures
Primary
Radiographic progression-free survival (rPFS)
Will be assessed using response evaluation criteria in solid tumors (RECIST 1.1), progression of bone lesions using Prostate Cancer Working Group 2 (PCWG2) criteria, or occurrence of death due to any cause. RECIST 1.1 progression requires at least a 20% increase in the sum of diameters of target lesions and/or unequivocal progression of existing non-target lesions. PCWG2 bone lesion progression requires appearance of two or more new lesions seen on bone scan compared with bone scan at randomization.
Time frame: From date of randomization to the first documentation of rPFS event, assessed up to 5 years
Secondary
Prostate specific antigen (PSA) response
Time frame: From study entry to first occurrence of rPFS or clinical progression, assessed up to 5 years
Alkaline phosphatase response
Time frame: From study entry to first occurrence of rPFS or clinical progression, assessed up to 5 years
RECIST response
Time frame: From study entry to first occurrence of rPFS or clinical progression, assessed up to 5 years
Progression-free survival
Time frame: From study entry to first occurrence of rPFS or clinical progression, assessed up to 5 years
OS
Time frame: From date of randomization to date of death due to any cause, assessed up to 5 years
Eligibility criteria
Study locations (174)
Highlands Oncology Group - Fayetteville
Fayetteville, Arkansas, 72703
Highlands Oncology Group - Rogers
Rogers, Arkansas, 72758
Highlands Oncology Group
Springdale, Arkansas, 72762
Tibor Rubin VA Medical Center
Long Beach, California, 90822
Beebe Medical Center
Lewes, Delaware, 19958
Beebe South Coastal Health Campus
Millville, Delaware, 19967
Helen F Graham Cancer Center
Newark, Delaware, 19713
Medical Oncology Hematology Consultants PA
Newark, Delaware, 19713
Christiana Care Health System-Christiana Hospital
Newark, Delaware, 19718
Beebe Health Campus
Rehoboth Beach, Delaware, 19971
Christiana Care Health System-Wilmington Hospital
Wilmington, Delaware, 19801
Holy Cross Hospital
Fort Lauderdale, Florida, 33308
Saint Alphonsus Cancer Care Center-Boise
Boise, Idaho, 83706
Saint Alphonsus Cancer Care Center-Caldwell
Caldwell, Idaho, 83605
Kootenai Health - Coeur d'Alene
Coeur d'Alene, Idaho, 83814
Idaho Urologic Institute-Meridian
Meridian, Idaho, 83642
Saint Alphonsus Cancer Care Center-Nampa
Nampa, Idaho, 83687
Kootenai Clinic Cancer Services - Post Falls
Post Falls, Idaho, 83854
Kootenai Clinic Cancer Services - Sandpoint
Sandpoint, Idaho, 83864
Illinois CancerCare-Bloomington
Bloomington, Illinois, 61704
Illinois CancerCare-Canton
Canton, Illinois, 61520
Memorial Hospital of Carbondale
Carbondale, Illinois, 62902
SIH Cancer Institute
Carterville, Illinois, 62918
Illinois CancerCare-Carthage
Carthage, Illinois, 62321
Centralia Oncology Clinic
Centralia, Illinois, 62801
Northwestern University
Chicago, Illinois, 60611
University of Illinois
Chicago, Illinois, 60612
Cancer Care Specialists of Illinois - Decatur
Decatur, Illinois, 62526
Decatur Memorial Hospital
Decatur, Illinois, 62526
Northwestern Medicine Cancer Center Kishwaukee
DeKalb, Illinois, 60115
Illinois CancerCare-Dixon
Dixon, Illinois, 61021
Crossroads Cancer Center
Effingham, Illinois, 62401
Illinois CancerCare-Eureka
Eureka, Illinois, 61530
Illinois CancerCare-Galesburg
Galesburg, Illinois, 61401
Western Illinois Cancer Treatment Center
Galesburg, Illinois, 61401
Northwestern Medicine Cancer Center Delnor
Geneva, Illinois, 60134
Northwestern Medicine Glenview Outpatient Center
Glenview, Illinois, 60026
Northwestern Medicine Grayslake Outpatient Center
Grayslake, Illinois, 60030
Illinois CancerCare-Kewanee Clinic
Kewanee, Illinois, 61443
Northwestern Medicine Lake Forest Hospital
Lake Forest, Illinois, 60045
Illinois CancerCare-Macomb
Macomb, Illinois, 61455
Cancer Care Center of O'Fallon
O'Fallon, Illinois, 62269
HSHS Saint Elizabeth's Hospital
O'Fallon, Illinois, 62269
Northwestern Medicine Orland Park
Orland Park, Illinois, 60462
Illinois CancerCare-Ottawa Clinic
Ottawa, Illinois, 61350
Illinois CancerCare-Pekin
Pekin, Illinois, 61554
Illinois CancerCare-Peoria
Peoria, Illinois, 61615
Methodist Medical Center of Illinois
Peoria, Illinois, 61636
Illinois CancerCare-Peru
Peru, Illinois, 61354
Valley Radiation Oncology
Peru, Illinois, 61354
Illinois CancerCare-Princeton
Princeton, Illinois, 61356
Southern Illinois University School of Medicine
Springfield, Illinois, 62702
Springfield Clinic
Springfield, Illinois, 62702
Memorial Medical Center
Springfield, Illinois, 62781
Northwestern Medicine Cancer Center Warrenville
Warrenville, Illinois, 60555
Illinois CancerCare - Washington
Washington, Illinois, 61571
Reid Health
Richmond, Indiana, 47374
Mercy Hospital
Cedar Rapids, Iowa, 52403
Oncology Associates at Mercy Medical Center
Cedar Rapids, Iowa, 52403
Christiana Care - Union Hospital
Elkton, Maryland, 21921
Trinity Health Saint Joseph Mercy Hospital Ann Arbor
Ann Arbor, Michigan, 48106
Trinity Health IHA Medical Group Hematology Oncology - Brighton
Brighton, Michigan, 48114
Trinity Health Medical Center - Brighton
Brighton, Michigan, 48114
Trinity Health IHA Medical Group Hematology Oncology - Canton
Canton, Michigan, 48188
Trinity Health Medical Center - Canton
Canton, Michigan, 48188
Caro Cancer Center
Caro, Michigan, 48723
Chelsea Hospital
Chelsea, Michigan, 48118
Trinity Health IHA Medical Group Hematology Oncology - Chelsea Hospital
Chelsea, Michigan, 48118
Hematology Oncology Consultants-Clarkston
Clarkston, Michigan, 48346
Newland Medical Associates-Clarkston
Clarkston, Michigan, 48346
Henry Ford Health Saint John Hospital
Detroit, Michigan, 48236
Great Lakes Cancer Management Specialists-Doctors Park
East China Township, Michigan, 48054
Genesee Cancer and Blood Disease Treatment Center
Flint, Michigan, 48503
Genesee Hematology Oncology PC
Flint, Michigan, 48503
Genesys Hurley Cancer Institute
Flint, Michigan, 48503
Hurley Medical Center
Flint, Michigan, 48503
Great Lakes Cancer Management Specialists-Van Elslander Cancer Center
Grosse Pointe Woods, Michigan, 48236
Henry Ford Saint John Hospital - Academic
Grosse Pointe Woods, Michigan, 48236
Henry Ford Saint John Hospital - Breast
Grosse Pointe Woods, Michigan, 48236
University of Michigan Health - Sparrow Lansing
Lansing, Michigan, 48912
Trinity Health Saint Mary Mercy Livonia Hospital
Livonia, Michigan, 48154
Great Lakes Cancer Management Specialists-Macomb Medical Campus
Macomb, Michigan, 48044
Henry Ford Warren Hospital - Breast Macomb
Macomb, Michigan, 48044
Saint Mary's Oncology/Hematology Associates of Marlette
Marlette, Michigan, 48453
Hope Cancer Center
Pontiac, Michigan, 48341
Michigan Healthcare Professionals Pontiac
Pontiac, Michigan, 48341
Newland Medical Associates-Pontiac
Pontiac, Michigan, 48341
Trinity Health Saint Joseph Mercy Oakland Hospital
Pontiac, Michigan, 48341
MyMichigan Medical Center Saginaw
Saginaw, Michigan, 48601
Oncology Hematology Associates of Saginaw Valley PC
Saginaw, Michigan, 48604
MyMichigan Medical Center Tawas
Tawas City, Michigan, 48764
Great Lakes Cancer Management Specialists-Macomb Professional Building
Warren, Michigan, 48093
Henry Ford Madison Heights Hospital - Breast
Warren, Michigan, 48093
Saint John Macomb-Oakland Hospital
Warren, Michigan, 48093
Saint Mary's Oncology/Hematology Associates of West Branch
West Branch, Michigan, 48661
Huron Gastroenterology PC
Ypsilanti, Michigan, 48106
Trinity Health IHA Medical Group Hematology Oncology Ann Arbor Campus
Ypsilanti, Michigan, 48197
Minnesota Oncology - Burnsville
Burnsville, Minnesota, 55337
Cambridge Medical Center
Cambridge, Minnesota, 55008
Mercy Hospital
Coon Rapids, Minnesota, 55433
Fairview Southdale Hospital
Edina, Minnesota, 55435
Fairview Clinics and Surgery Center Maple Grove
Maple Grove, Minnesota, 55369
Minnesota Oncology Hematology PA-Maplewood
Maplewood, Minnesota, 55109
Saint John's Hospital - Healtheast
Maplewood, Minnesota, 55109
Abbott-Northwestern Hospital
Minneapolis, Minnesota, 55407
Hennepin County Medical Center
Minneapolis, Minnesota, 55415
Health Partners Inc
Minneapolis, Minnesota, 55454
Monticello Cancer Center
Monticello, Minnesota, 55362
New Ulm Medical Center
New Ulm, Minnesota, 56073
Fairview Northland Medical Center
Princeton, Minnesota, 55371
North Memorial Medical Health Center
Robbinsdale, Minnesota, 55422
Park Nicollet Clinic - Saint Louis Park
Saint Louis Park, Minnesota, 55416
Regions Hospital
Saint Paul, Minnesota, 55101
United Hospital
Saint Paul, Minnesota, 55102
Saint Francis Regional Medical Center
Shakopee, Minnesota, 55379
Lakeview Hospital
Stillwater, Minnesota, 55082
Ridgeview Medical Center
Waconia, Minnesota, 55387
Rice Memorial Hospital
Willmar, Minnesota, 56201
Minnesota Oncology Hematology PA-Woodbury
Woodbury, Minnesota, 55125
Fairview Lakes Medical Center
Wyoming, Minnesota, 55092
University of Mississippi Medical Center
Jackson, Mississippi, 39216
Saint Francis Medical Center
Cape Girardeau, Missouri, 63703
Southeast Cancer Center
Cape Girardeau, Missouri, 63703
Parkland Health Center - Farmington
Farmington, Missouri, 63640
Sainte Genevieve County Memorial Hospital
Sainte Genevieve, Missouri, 63670
Missouri Baptist Medical Center
St Louis, Missouri, 63131
Missouri Baptist Sullivan Hospital
Sullivan, Missouri, 63080
BJC Outpatient Center at Sunset Hills
Sunset Hills, Missouri, 63127
Community Hospital of Anaconda
Anaconda, Montana, 59711
Billings Clinic Cancer Center
Billings, Montana, 59101
Bozeman Health Deaconess Hospital
Bozeman, Montana, 59715
Benefis Sletten Cancer Institute
Great Falls, Montana, 59405
Great Falls Clinic
Great Falls, Montana, 59405
Kalispell Regional Medical Center
Kalispell, Montana, 59901
Community Medical Center
Missoula, Montana, 59804
Nebraska Medicine-Bellevue
Bellevue, Nebraska, 68123
Nebraska Medicine-Village Pointe
Omaha, Nebraska, 68118
University of Nebraska Medical Center
Omaha, Nebraska, 68198
Indu and Raj Soin Medical Center
Beavercreek, Ohio, 45431
Saint Elizabeth Boardman Hospital
Boardman, Ohio, 44512
Dayton Physicians LLC-Miami Valley South
Centerville, Ohio, 45459
Oncology Hematology Care Inc-Kenwood
Cincinnati, Ohio, 45236
Dayton Physician LLC - Englewood
Dayton, Ohio, 45415
Armes Family Cancer Center
Findlay, Ohio, 45840
Blanchard Valley Hospital
Findlay, Ohio, 45840
Orion Cancer Care
Findlay, Ohio, 45840
Dayton Physicians LLC-Atrium
Franklin, Ohio, 45005
Dayton Physicians LLC-Wayne
Greenville, Ohio, 45331
Wayne Hospital
Greenville, Ohio, 45331
Greater Dayton Cancer Center
Kettering, Ohio, 45409
Kettering Medical Center
Kettering, Ohio, 45429
Dayton Physicians LLC - Troy
Troy, Ohio, 45373
Saint Joseph Warren Hospital
Warren, Ohio, 44484
Saint Elizabeth Youngstown Hospital
Youngstown, Ohio, 44501
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, 73104
Saint Alphonsus Cancer Care Center-Baker City
Baker City, Oregon, 97814
Saint Alphonsus Cancer Care Center-Ontario
Ontario, Oregon, 97914
Lehigh Valley Hospital-Cedar Crest
Allentown, Pennsylvania, 18103
Lehigh Valley Hospital - Muhlenberg
Bethlehem, Pennsylvania, 18017
Christiana Care Health System-Concord Health Center
Chadds Ford, Pennsylvania, 19317
Pocono Medical Center
East Stroudsburg, Pennsylvania, 18301
Lehigh Valley Hospital-Hazleton
Hazleton, Pennsylvania, 18201
The West Clinic - Wolf River
Germantown, Tennessee, 38138
MD Anderson in The Woodlands
Conroe, Texas, 77384
Lyndon Baines Johnson General Hospital
Houston, Texas, 77026-1967
M D Anderson Cancer Center
Houston, Texas, 77030
MD Anderson West Houston
Houston, Texas, 77079
MD Anderson League City
League City, Texas, 77573
MD Anderson in Sugar Land
Sugar Land, Texas, 77478
VCU Massey Cancer Center at Stony Point
Richmond, Virginia, 23235
Virginia Commonwealth University/Massey Cancer Center
Richmond, Virginia, 23298
Cancer Center of Western Wisconsin
New Richmond, Wisconsin, 54017
Billings Clinic-Cody
Cody, Wyoming, 82414
Welch Cancer Center
Sheridan, Wyoming, 82801