Docetaxel Addition in Metastatic Castrate-Sensitive Prostate Cancer (ASPIRE)
Summary
This phase III trial compares the effect of adding docetaxel to hormonal therapy and apalutamide versus hormonal therapy and apalutamide alone in treating patients with prostate cancer that has spread from where it first started (primary site) to other places in the body (metastatic). Docetaxel is in a class of medications called taxanes. It stops tumor cells from growing and dividing and may kill them. Hormone therapy for prostate cancer, also called androgen deprivation therapy (ADT), uses surgery or drugs to lower the levels of male sex hormones in a man's body. This helps slow the growth of prostate cancer. Apalutamide is in a class of medications called androgen receptor inhibitors. It works by blocking the effects of androgen (a male reproductive hormone) to stop the growth and spread of tumor cells. Giving docetaxel in addition to the usual treatment of hormonal therapy and apalutamide may work better in treating patients with metastatic prostate cancer than the usual treatment alone.
Detailed description
PRIMARY OBJECTIVE: I. To determine if the addition of docetaxel to androgen deprivation therapy and apalutamide improves overall survival for men with metastatic castrate sensitive prostate cancer. SECONDARY OBJECTIVES: I. To determine if the addition of docetaxel to androgen deprivation therapy and apalutamide improves overall survival for men whose cancers have loss or inactivating mutations of TP53, PTEN, or RB1. II. To determine if the addition of docetaxel to ADT plus apalutamide improves the time to radiographic progression per Prostate Cancer Working Group 3 (PCWG3) guidelines. III. To determine the time to castration-resistant prostate cancer (CRPC) between arms. IV. To determine symptomatic skeletal event free survival (SSE-FS) between arms. V. To determine the safety and tolerability of the triplet versus doublet using Common Terminology Criteria for Adverse Events (CTCAE) version (v)5.0. VI. To determine radiographic progression free survival (rPFS), and overall survival (OS) in patients by the stratification factors a) volume/timing of disease (metachronous high volume, synchronous high volume, and synchronous low volume metastases on conventional imaging) and b) tumor suppressor gene alteration status (0 versus \[vs\] 1 vs 2+) between arms. VII. To determine prostate specific antigen (PSA) 90 response rate at 6 weeks and 6 months between arms. VIII. To determine time to PSA progression by PCWG3 criteria between arms. IX. To determine objective response rate (ORR) in patients with measurable disease between arms. EXPLORATORY OBJECTIVES: I. To determine the time to worsening of physical symptoms of disease based on functional assessment of cancer therapy/National Comprehensive Cancer Network prostate cancer symptom index 17 item questionnaire (NCCN-FACT FPSI-17) between arms. II. To compare quality of life as measured by Functional Assessment of Cancer Therapy-Prostate (FACT-P) trial outcome index in patients with metastatic castrate-sensitive prostate cancer (mCSPC) who receive ADT + apalutamide + docetaxel vs ADT + apalutamide at the 24-month time point. III. To compare quality of life as measured by other scales of the FACT-P in the two arms. IV. To compare quality of life as measured by FACT-P total outcome index in the two arms at other timepoints. V. To compare pain severity and interference as measured by the Brief Pain Inventory Short Form (BPI-SF) in the two arms. VI. To compare quality-adjusted life years which accounts for survival and utility (measured by European Quality of Life Five Dimension Five Level Scale \[EQ-5D-5L\]) in the two arms. VII. To correlate baseline volume of disease on prostate-specific membrane antigen-positron emission tomography/computed tomography (PSMA-PET/CT) with baseline volume of disease on conventional imaging (CI). VIII. To determine if baseline PSMA-PET/CT and CI are individually and jointly associated with OS, progression-free survival (PFS), PSA90 response, and PSA \< 0.2 ng/ml after 6 months, and to estimate its clinical relevance when compared to these well characterized prognostic endpoints. IX. To correlate 6-month PSA level with the presence/absence and volume of residual disease on PSMA-PET/CT after 6 months of doublet or triplet therapy. X. To correlate the concordance of radiographic progression on CI versus PSMA-PET/CT at the time of PSA progression. XI. To determine rPFS, time to castration resistance, OS based on thresholds of volume of disease, and prostate-specific membrane antigen (PSMA) uptake (standardized uptake value \[SUV\]) based on baseline PSMA-PET/CT scan. XII. To compare rPFS, time to castration resistance, and OS between arms in patients with de novo metastatic disease having received primary directed radiation therapy. XIII. To determine rPFS, time to castration resistance, and OS correlation with PSA response at 6 weeks and 6 months. XIV. To compare the impact of treatment on aging trajectory, as measured by the change in Deficit-Accumulation Frailty Index (DAFI) from baseline, 6- and 12-months, in the two arms. OUTLINE: Patients are randomized to 1 of 2 arms. ARM 1: Patients receive ADT at the discretion of the investigator and apalutamide orally (PO) once daily (QD). Cycles repeat every 12 weeks in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo computed tomography (CT) scan or magnetic resonance imaging (MRI) and bone scan throughout the study. Patients may optionally undergo prostate-specific membrane antigen-positron emission tomography (PSMA-PET) scans and blood sample collection throughout the study. ARM 2: Patients receive ADT at the discretion of the investigator and apalutamide PO QD. Cycles repeat every 12 weeks in the absence of disease progression or unacceptable toxicity. Patients also receive docetaxel intravenously (IV) over 1 hour every 21 days for up to 6 doses. Additionally, patients undergo CT scan or MRI and bone scan throughout the study. Patients may optionally undergo PSMA-PET scans and blood sample collection throughout the study. After completion of study treatment, patients are followed up every 6 months for up to 10 years.
Arms & interventions
- DrugAndrogen Therapy
Given ADT
- DrugApalutamide
Given PO
- DrugDocetaxel
Given IV
- ProcedureComputed Tomography
Undergo CT
- ProcedureMagnetic Resonance Imaging
Undergo MRI
- ProcedureBone Scan
Undergo Bone Scan
- ProcedurePSMA PET Scan
Undergo PSMA PET Scan
- ProcedureBiospecimen Collection
Undergo blood sample collection
- OtherQuestionnaire Administration
undergo Questionnaire Administration
Outcome measures
Primary
Overall survival (OS)
Will determine OS. To assess the potential OS benefit from the triplet therapy, a group sequential efficacy/futility monitoring design will be employed. The planned analyses for OS will be tested using a one-sided type 1 error rate of 0.025. An intent-to-treat approach will be used to evaluate OS between treatments. The stratified logrank test will be the primary analysis to compare OS between treatments. The Kaplan-Meier estimate will be used to evaluate the within treatment OS distributions. In addition, the proportional hazards model will be applied to assess the treatment comparison adjusting for important covariates in predicting OS.
Time frame: From randomization to death due to any cause, assessed up to 10 years
Secondary
Overall Survival (OS)
Time frame: From randomization to death due to any cause, assessed up to 10 years
Radiographic progression
Time frame: From randomization to first documentation of radiographic progressive disease or death due to any cause, assessed up to 10 years
Castration-resistant prostate cancer (CRPC)
Time frame: Time to prostate-specific antigen progression with serum testosterone being at castrate level < 0.50 ng/mL, or the time to progression by soft tissue/visceral lesions or time to progression by bone lesions per PCWG3 guidelines, assessed up to 10 years
Symptomatic skeletal event free survival (SSE-FS)
Time frame: From randomization to first occurrence of SSE or death from any cause, assessed up to 10 years
Worsening of physical symptoms of disease
Time frame: up to 10 years
Incidence of adverse events
Time frame: up to 10 years
Radiographic progression free survival (rPFS)
Time frame: From randomization to first documentation of radiographic progressive disease or death due to any cause, assessed up to 10 years
OS
Time frame: Will determine OS in patients by the stratification factors a) timing/volume of disease 1) metachronous high volume, 2) synchronous high volume and 3) synchronous low volume metastases on conventional imaging. To assess the potential OS benefit from the
Prostate specific antigen (PSA) 90 response rate
Time frame: At 6 weeks and 6 months
Time to PSA progression
Time frame: From randomization to the date of PSA progression based on PCWG3 criteria, assessed up to 10 years
Objective response rate (ORR)
Time frame: up to 10 years
Eligibility criteria
Study locations (194)
Banner University Medical Center - Tucson
Tucson, Arizona, 85719
University of Arizona Cancer Center-North Campus
Tucson, Arizona, 85719
Kaiser Permanente Dublin
Dublin, California, 94568
Kaiser Permanente-Fremont
Fremont, California, 94538
Kaiser Permanente Fresno Orchard Plaza
Fresno, California, 93720
UC San Diego Moores Cancer Center
La Jolla, California, 92093
Kaiser Permanente- Modesto MOB II
Modesto, California, 95356
Kaiser Permanente-Modesto
Modesto, California, 95356
Kaiser Permanente-Oakland
Oakland, California, 94611
Eisenhower Medical Center
Rancho Mirage, California, 92270
Kaiser Permanente-Roseville
Roseville, California, 95661
Kaiser Permanente Downtown Commons
Sacramento, California, 95814
Kaiser Permanente-South Sacramento
Sacramento, California, 95823
UC San Diego Medical Center - Hillcrest
San Diego, California, 92103
Kaiser Permanente-San Francisco
San Francisco, California, 94115
Kaiser Permanente-Santa Teresa-San Jose
San Jose, California, 95119
Kaiser Permanente San Leandro
San Leandro, California, 94577
Kaiser San Rafael-Gallinas
San Rafael, California, 94903
Kaiser Permanente Medical Center - Santa Clara
Santa Clara, California, 95051
Kaiser Permanente-Santa Rosa
Santa Rosa, California, 95403
Kaiser Permanente-South San Francisco
South San Francisco, California, 94080
Kaiser Permanente-Vallejo
Vallejo, California, 94589
Kaiser Permanente-Walnut Creek
Walnut Creek, California, 94596
Kaiser Permanente-Franklin
Denver, Colorado, 80205
Saint Mary's Hospital and Regional Medical Center
Grand Junction, Colorado, 81501
Kaiser Permanente-Rock Creek
Lafayette, Colorado, 80026
Kaiser Permanente-Lone Tree
Lone Tree, Colorado, 80124
Bayhealth Hospital Kent Campus
Dover, Delaware, 19901
Bayhealth Hospital Sussex Campus
Milford, Delaware, 19963
MedStar Georgetown University Hospital
Washington D.C., District of Columbia, 20007
MedStar Washington Hospital Center
Washington D.C., District of Columbia, 20010
Malcom Randall Veterans Administration Medical Center
Gainesville, Florida, 32610
Kaiser Permanente Moanalua Medical Center
Honolulu, Hawaii, 96819
Saint Luke's Cancer Institute - Boise
Boise, Idaho, 83712
Kootenai Health - Coeur d'Alene
Coeur d'Alene, Idaho, 83814
Saint Luke's Cancer Institute - Fruitland
Fruitland, Idaho, 83619
Saint Luke's Cancer Institute - Meridian
Meridian, Idaho, 83642
Saint Luke's Cancer Institute - 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
Illinois CancerCare-Carthage
Carthage, Illinois, 62321
Centralia Oncology Clinic
Centralia, Illinois, 62801
Rush MD Anderson Cancer Center
Chicago, Illinois, 60612
University of Illinois
Chicago, Illinois, 60612
Carle at The Riverfront
Danville, Illinois, 61832
Cancer Care Specialists of Illinois - Decatur
Decatur, Illinois, 62526
Decatur Memorial Hospital
Decatur, Illinois, 62526
Illinois CancerCare-Dixon
Dixon, Illinois, 61021
Carle Physician Group-Effingham
Effingham, Illinois, 62401
Crossroads Cancer Center
Effingham, Illinois, 62401
Illinois CancerCare-Eureka
Eureka, Illinois, 61530
Illinois CancerCare-Galesburg
Galesburg, Illinois, 61401
Illinois CancerCare-Kewanee Clinic
Kewanee, Illinois, 61443
Illinois CancerCare-Macomb
Macomb, Illinois, 61455
Carle Physician Group-Mattoon/Charleston
Mattoon, Illinois, 61938
Carle BroMenn Medical Center
Normal, Illinois, 61761
Carle Cancer Institute Normal
Normal, Illinois, 61761
Cancer Care Center of O'Fallon
O'Fallon, Illinois, 62269
HSHS Saint Elizabeth's Hospital
O'Fallon, Illinois, 62269
Illinois CancerCare-Ottawa Clinic
Ottawa, Illinois, 61350
Illinois CancerCare-Pekin
Pekin, Illinois, 61554
Illinois CancerCare-Peoria
Peoria, Illinois, 61615
Illinois CancerCare-Peru
Peru, Illinois, 61354
Illinois CancerCare-Princeton
Princeton, Illinois, 61356
Memorial Hospital East
Shiloh, Illinois, 62269
Southern Illinois University School of Medicine
Springfield, Illinois, 62702
Springfield Clinic
Springfield, Illinois, 62702
Springfield Memorial Hospital
Springfield, Illinois, 62781
Carle Cancer Center
Urbana, Illinois, 61801
Illinois CancerCare - Washington
Washington, Illinois, 61571
Mary Greeley Medical Center
Ames, Iowa, 50010
McFarland Clinic - Ames
Ames, Iowa, 50010
McFarland Clinic - Boone
Boone, Iowa, 50036
Mercy Hospital
Cedar Rapids, Iowa, 52403
Oncology Associates at Mercy Medical Center
Cedar Rapids, Iowa, 52403
McFarland Clinic - Trinity Cancer Center
Fort Dodge, Iowa, 50501
McFarland Clinic - Jefferson
Jefferson, Iowa, 50129
McFarland Clinic - Marshalltown
Marshalltown, Iowa, 50158
HaysMed
Hays, Kansas, 67601
Lawrence Memorial Hospital
Lawrence, Kansas, 66044
The University of Kansas Cancer Center - Olathe
Olathe, Kansas, 66061
University of Kansas Cancer Center-Overland Park
Overland Park, Kansas, 66210
Salina Regional Health Center
Salina, Kansas, 67401
University of Kansas Health System Saint Francis Campus
Topeka, Kansas, 66606
University of Kansas Hospital-Westwood Cancer Center
Westwood, Kansas, 66205
Trinity Health IHA Medical Group Hematology Oncology - Brighton
Brighton, Michigan, 48114
Trinity Health IHA Medical Group Hematology Oncology - Canton
Canton, Michigan, 48188
Trinity Health IHA Medical Group Hematology Oncology - Chelsea Hospital
Chelsea, Michigan, 48118
OSF Saint Francis Hospital and Medical Group
Escanaba, Michigan, 49829
Genesys Hurley Cancer Institute
Flint, Michigan, 48503
Hurley Medical Center
Flint, Michigan, 48503
University of Michigan Health - Sparrow Lansing
Lansing, Michigan, 48912
Trinity Health Saint Mary Mercy Livonia Hospital
Livonia, Michigan, 48154
Trinity Health Saint Joseph Mercy Oakland Hospital
Pontiac, Michigan, 48341
Trinity Health IHA Medical Group Hematology Oncology Ann Arbor Campus
Ypsilanti, Michigan, 48197
Sanford Joe Lueken Cancer Center
Bemidji, Minnesota, 56601
Coborn Cancer Center at Saint Cloud Hospital
Saint Cloud, Minnesota, 56303
Saint Francis Medical Center
Cape Girardeau, Missouri, 63703
Siteman Cancer Center at Saint Peters Hospital
City of Saint Peters, Missouri, 63376
Siteman Cancer Center at West County Hospital
Creve Coeur, Missouri, 63141
University Health Truman Medical Center
Kansas City, Missouri, 64108
University of Kansas Cancer Center - Briarcliff
Kansas City, Missouri, 64116
University of Kansas Cancer Center - North
Kansas City, Missouri, 64154
University of Kansas Cancer Center - Lee's Summit
Lee's Summit, Missouri, 64064
Washington University School of Medicine
St Louis, Missouri, 63110
Mercy Hospital South
St Louis, Missouri, 63128
Siteman Cancer Center-South County
St Louis, Missouri, 63129
Siteman Cancer Center at Christian Hospital
St Louis, Missouri, 63136
Mercy Hospital Saint Louis
St Louis, Missouri, 63141
Community Hospital of Anaconda
Anaconda, Montana, 59711
Billings Clinic Cancer Center
Billings, Montana, 59101
Saint Vincent Frontier Cancer Center
Billings, Montana, 59102
Bozeman Health Deaconess Hospital
Bozeman, Montana, 59715
Benefis Sletten Cancer Institute
Great Falls, Montana, 59405
Logan Health Medical Center
Kalispell, Montana, 59901
Community Medical Center
Missoula, Montana, 59804
Memorial Sloan Kettering Basking Ridge
Basking Ridge, New Jersey, 07920
Jefferson Cherry Hill Hospital
Cherry Hill, New Jersey, 08002
Memorial Sloan Kettering Monmouth
Middletown, New Jersey, 07748
Memorial Sloan Kettering Bergen
Montvale, New Jersey, 07645
Sidney Kimmel Cancer Center Washington Township
Sewell, New Jersey, 08080
Roswell Park Cancer Institute
Buffalo, New York, 14263
Memorial Sloan Kettering Commack
Commack, New York, 11725
Guthrie Cortland Memorial Hospital
Cortland, New York, 13045
Memorial Sloan Kettering Westchester
Harrison, New York, 10604
Mount Sinai Hospital
New York, New York, 10029
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
Stony Brook University Medical Center
Stony Brook, New York, 11794
Memorial Sloan Kettering Nassau
Uniondale, New York, 11553
Duke University Medical Center
Durham, North Carolina, 27710
FirstHealth of the Carolinas-Moore Regional Hospital
Pinehurst, North Carolina, 28374
Sanford Bismarck Medical Center
Bismarck, North Dakota, 58501
Sanford Broadway Medical Center
Fargo, North Dakota, 58122
Sanford Roger Maris Cancer Center
Fargo, North Dakota, 58122
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43210
ProMedica Flower Hospital
Sylvania, Ohio, 43560
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, 73104
Saint Vincent Hospital
Erie, Pennsylvania, 16544
Jefferson Hospital
Jefferson Hills, Pennsylvania, 15025
Forbes Hospital
Monroeville, Pennsylvania, 15146
Allegheny Valley Hospital
Natrona Heights, Pennsylvania, 15065
Thomas Jefferson University Hospital
Philadelphia, Pennsylvania, 19107
Jefferson Torresdale Hospital
Philadelphia, Pennsylvania, 19114
Jefferson Methodist Hospital
Philadelphia, Pennsylvania, 19148
Allegheny General Hospital
Pittsburgh, Pennsylvania, 15212
West Penn Hospital
Pittsburgh, Pennsylvania, 15224
Guthrie Medical Group PC-Robert Packer Hospital
Sayre, Pennsylvania, 18840
Wexford Health and Wellness Pavilion
Wexford, Pennsylvania, 15090
Asplundh Cancer Pavilion
Willow Grove, Pennsylvania, 19090
Saint Francis Hospital
Greenville, South Carolina, 29601
Saint Francis Cancer Center
Greenville, South Carolina, 29607
Self Regional Healthcare
Greenwood, South Carolina, 29646
Rapid City Regional Hospital
Rapid City, South Dakota, 57701
Sanford Cancer Center Oncology Clinic
Sioux Falls, South Dakota, 57104
Sanford USD Medical Center - Sioux Falls
Sioux Falls, South Dakota, 57117-5134
UT Southwestern Simmons Cancer Center - RedBird
Dallas, Texas, 75237
UT Southwestern/Simmons Cancer Center-Dallas
Dallas, Texas, 75390
UT Southwestern/Simmons Cancer Center-Fort Worth
Fort Worth, Texas, 76104
UT Southwestern Clinical Center at Richardson/Plano
Richardson, Texas, 75080
Intermountain Medical Center
Murray, Utah, 84107
LDS Hospital
Salt Lake City, Utah, 84143
Saint George Regional Medical Center
St. George, Utah, 84770
Central Vermont Medical Center/National Life Cancer Treatment
Berlin Corners, Vermont, 05602
University of Vermont Medical Center
Burlington, Vermont, 05401
University of Vermont and State Agricultural College
Burlington, Vermont, 05405
Hematology Oncology Associates of Fredericksburg Inc
Fredericksburg, Virginia, 22408
VCU Massey Cancer Center at Stony Point
Richmond, Virginia, 23235
VCU Massey Comprehensive Cancer Center
Richmond, Virginia, 23298
VCU Health Tappahannock Hospital
Tappahannock, Virginia, 22560
West Virginia University Charleston Division
Charleston, West Virginia, 25304
ThedaCare Regional Cancer Center
Appleton, Wisconsin, 54911
Ascension Saint Elizabeth Hospital
Appleton, Wisconsin, 54915
Ascension Southeast Wisconsin Hospital - Elmbrook Campus
Brookfield, Wisconsin, 53045
Ascension Calumet Hospital
Chilton, Wisconsin, 53014
Ascension Saint Francis - Reiman Cancer Center
Franklin, Wisconsin, 53132
Saint Vincent Hospital Cancer Center Green Bay
Green Bay, Wisconsin, 54301
Saint Vincent Hospital Cancer Center at Saint Mary's
Green Bay, Wisconsin, 54303
William S Middleton VA Medical Center
Madison, Wisconsin, 53705
Froedtert Menomonee Falls Hospital
Menomonee Falls, Wisconsin, 53051
Ascension Columbia Saint Mary's Hospital Ozaukee
Mequon, Wisconsin, 53097
Ascension Columbia Saint Mary's Hospital - Milwaukee
Milwaukee, Wisconsin, 53211
Medical College of Wisconsin
Milwaukee, Wisconsin, 53226
Froedtert and MCW Moorland Reserve Health Center
New Berlin, Wisconsin, 53151
Drexel Town Square Health Center
Oak Creek, Wisconsin, 53154
Saint Vincent Hospital Cancer Center at Oconto Falls
Oconto Falls, Wisconsin, 54154
Ascension Mercy Hospital
Oshkosh, Wisconsin, 54904
Ascension All Saints Hospital
Racine, Wisconsin, 53405
Saint Vincent Hospital Cancer Center at Sheboygan
Sheboygan, Wisconsin, 53081
Sheboygan Physicians Group
Sheboygan, Wisconsin, 53081
Saint Vincent Hospital Cancer Center at Sturgeon Bay
Sturgeon Bay, Wisconsin, 54235-1495
Ascension Medical Group Southeast Wisconsin - Mayfair Road
Wauwatosa, Wisconsin, 53226
Froedtert West Bend Hospital/Kraemer Cancer Center
West Bend, Wisconsin, 53095