Testing the Addition of Docetaxel (Chemotherapy) to the Usual Treatment (Hormonal Therapy and Apalutamide) for Metastatic Prostate Cancer, ASPIRE Trial
Purpose
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.
Conditions
- Castration-Sensitive Prostate Carcinoma
- Metastatic Prostate Adenocarcinoma
- Stage IVB Prostate Cancer AJCC v8
Eligibility
- Eligible Ages
- Over 18 Years
- Eligible Sex
- Male
- Accepts Healthy Volunteers
- No
Criteria
Inclusion Criteria:
- Documentation of disease:
* Histologically or cytologically confirmed adenocarcinoma of the prostate without
small cell histology
- Must have had evidence of metastatic disease (American Joint Committee on Cancer
[AJCC] metastasis [M]1 disease) based on conventional CT/MRI and/or bone scan. This
will be defined as:
- Bone metastases detected by CT, radionuclide technetium-99 (99Tc)- methylene
bisphosphonate bone scan, or MRI as defined by PCWG3 criteria; OR
- Non-pelvic lymph node metastases (measurable lymph nodes above the aortic
bifurcation; lymph nodes are measurable if the short axis diameter is ≥ 15 mm)
detected on CT or MRI as defined by Response Evaluation Criteria in Solid
Tumors (RECIST) version 1.1. Subjects with regional lymph node metastases only
(nodes [N]1, below the aortic bifurcation) will not be eligible for the study;
OR
- Visceral or soft tissue metastases detected on CT or MRI as defined by RECIST
version 1.1. Soft tissue/visceral lesions are measurable if the long axis
diameter is ≥ 10 mm
- Evidence of metastatic disease by PSMA-PET only and not visible by CT,
radionuclide bone scan, or MRI will not satisfy eligibility criteria
- No metachronous low-volume disease (defined as recurrent metastatic disease after
definitive treatment of prostate primary) and with ≤ 4 bone metastasis and no
visceral metastasis on conventional imaging by CT, radionuclide 99Tc-biphosphonate
bone scan, or MRI)
- Next generation sequencing (NGS) results from any tissue based Clinical Laboratory
Improvement Act (CLIA) test must be available at the time of registration. NGS from
soft tissue or visceral lesion if available is preferred. NGS from bone or primary
prostate will be accepted. Patients with failed NGS testing are not eligible
- Prior treatment
- ADT (luteinizing hormone-releasing hormone [LHRH] agonist/antagonist or
orchiectomy) with or without first generation anti-androgen, or
second-generation androgen receptor signaling inhibitor (ARSI) within 120 days
of registration is permitted. No washout period will be needed for the first
generation- androgen or ARSI prior to registration. Anti-androgen treatment is
only permitted if used within 120 days of registration
- No prior chemotherapy for prostate cancer
- Age ≥ 18 years
- Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
- Absolute neutrophil count (ANC) ≥ 1,500/mm^3
- Hemoglobin ≥ 9.0 g/dL
- Platelet count ≥ 100,000/mm^3
- Total bilirubin ≤ 1 x upper limit of normal (ULN) (Note: In subjects with Gilbert's
syndrome, if total bilirubin is > 1.5 × ULN, measure direct and indirect bilirubin
and if direct bilirubin is ≤ 1 × ULN, subject may be eligible)
- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase
[SGOT])/alanine aminotransferase (ALT) (serum glutamate transaminase [SGT]) ≤ 1.5 x
upper limit of normal (ULN)
- Calculated (Calc.) creatinine clearance > 30 mL/min
- Serum potassium ≥ 3.5 mmol/L
- Comorbid conditions
- Patients with a prior or concurrent malignancy whose natural history or
treatment does not have the potential to interfere with the safety or efficacy
assessment of the investigational regimen are eligible for this trial
- Leptomeningeal metastases: Patients with treated leptomeningeal metastases are
eligible if follow-up brain imaging 30 days after central nervous system
(CNS)-directed therapy shows no evidence of progression
- HIV: Patients with known HIV infection on effective anti-retroviral therapy
with undetectable viral load within 6 months prior to registration are eligible
for this trial
- Hepatitis B: For patients with evidence of chronic hepatitis B virus (HBV)
infection, the HBV viral load must be undetectable on suppressive therapy, if
indicated
- Hepatitis C: Patients with a history of hepatitis C virus (HCV) infection must
have been treated and cured. For patients with HCV infection who are currently
on treatment, they are eligible if they have an undetectable HCV viral load
- No seizure or known condition that may pre-dispose to seizure (e.g. prior
stroke within 1 year to randomization, brain arteriovenous malformation or
condition requiring CNS surgery or radiation therapy)
- Patients with known history or current symptoms of cardiac disease, or history
of treatment with cardiotoxic agents, should have a clinical risk assessment of
cardiac function using the New York Heart Association functional
classification. To be eligible for this trial, patients should be class II or
better. Any condition that in the opinion of the investigator, would preclude
participation in this study. Patients with stable asymptomatic deep venous
thromboembolism on stable anti-coagulation will be eligible
- Hypertension: Subjects with uncontrolled hypertension as indicated by a resting
systolic blood pressure (BP) >= 160 mmHg or diastolic BP >= 100 mmHg despite
medical management are not permitted to register
- Allergies: Subjects with known hypersensitivity to any of the study drugs, or
excipients in the formulation of the study drugs are not permitted to register
- Concomitant medications
- Chronic concomitant treatment with strong inhibitors of cytochrome P450 3A4
(CYP3A4) is not allowed on this study. Patients on strong CYP3A4 inhibitors
must discontinue the drug prior to registration on the study. See Section 8.1.9
for more information
- Chronic concomitant treatment with strong CYP3A4 inducers is not allowed.
Patients must discontinue the drug 14 days prior to the start of study
treatment
- Medications known to lower the seizure threshold must be discontinued or
substituted prior to study entry. See Section 8.1.9 for more information
- Patient agrees to use a condom (even men with vasectomies) and another effective
method of birth control if having sex with a woman of childbearing potential or
agrees to use a condom if having sex with a woman who is pregnant while on study
drug and for 3 months following the last dose of study drug. Must also agree not to
donate sperm during the study and for 3 months after receiving the last dose of
study drug
Study Design
- Phase
- Phase 3
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel Assignment
- Primary Purpose
- Treatment
- Masking
- None (Open Label)
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Active Comparator Arm 1 (ADT, apalutamide) |
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. 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. |
|
|
Experimental Arm 2 (ADT, apalutamide, docetaxel) |
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 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. |
|
Recruiting Locations
Tucson, Arizona 85719
Tucson, Arizona 85719
Dublin, California 94568
Site Public Contact
877-642-4691
Fremont, California 94538
Fresno, California 93720
Site Public Contact
833-574-2273
La Jolla, California 92093
Modesto, California 95356
Site Public Contact
877-642-4691
Modesto, California 95356
Oakland, California 94611
Rancho Mirage, California 92270
Site Public Contact
760-834-3798
Roseville, California 95661
Sacramento, California 95814
Sacramento, California 95823
San Diego, California 92103
San Francisco, California 94115
San Jose, California 95119
San Leandro, California 94577
San Rafael, California 94903
Santa Clara, California 95051
Santa Rosa, California 95403
South San Francisco, California 94080
Vallejo, California 94589
Walnut Creek, California 94596
Denver, Colorado 80205
Grand Junction, Colorado 81501
Lafayette, Colorado 80026
Lone Tree, Colorado 80124
Washington D.C., District of Columbia 20007
Site Public Contact
202-444-2223
Washington D.C., District of Columbia 20010
Site Public Contact
202-877-8839
Gainesville, Florida 32610
Honolulu, Hawaii 96819
Boise, Idaho 83712
Coeur d'Alene, Idaho 83814
Fruitland, Idaho 83619
Meridian, Idaho 83642
Nampa, Idaho 83687
Post Falls, Idaho 83854
Sandpoint, Idaho 83864
Bloomington, Illinois 61704
Canton, Illinois 61520
Carthage, Illinois 62321
Centralia, Illinois 62801
Chicago, Illinois 60612
Chicago, Illinois 60612
Site Public Contact
312-355-3046
Danville, Illinois 61832
Decatur, Illinois 62526
Decatur, Illinois 62526
Dixon, Illinois 61021
Site Public Contact
815-285-7800
Effingham, Illinois 62401
Effingham, Illinois 62401
Eureka, Illinois 61530
Galesburg, Illinois 61401
Kewanee, Illinois 61443
Macomb, Illinois 61455
Mattoon, Illinois 61938
Normal, Illinois 61761
Normal, Illinois 61761
O'Fallon, Illinois 62269
O'Fallon, Illinois 62269
Ottawa, Illinois 61350
Pekin, Illinois 61554
Peoria, Illinois 61615
Peru, Illinois 61354
Princeton, Illinois 61356
Shiloh, Illinois 62269
Springfield, Illinois 62702
Site Public Contact
217-545-7929
Springfield, Illinois 62702
Site Public Contact
800-444-7541
Springfield, Illinois 62781
Urbana, Illinois 61801
Washington, Illinois 61571
Ames, Iowa 50010
Site Public Contact
515-956-4132
Ames, Iowa 50010
Cedar Rapids, Iowa 52403
Site Public Contact
319-365-4673
Cedar Rapids, Iowa 52403
Site Public Contact
319-363-2690
Fort Dodge, Iowa 50501
Site Public Contact
515-956-4132
Marshalltown, Iowa 50158
Site Public Contact
515-956-4132
Hays, Kansas 67601
Site Public Contact
785-623-5774
Lawrence, Kansas 66044
Olathe, Kansas 66061
Overland Park, Kansas 66210
Salina, Kansas 67401
Topeka, Kansas 66606
Site Public Contact
785-295-8000
Westwood, Kansas 66205
Brighton, Michigan 48114
Canton, Michigan 48188
Chelsea, Michigan 48118
Escanaba, Michigan 49829
Flint, Michigan 48503
Flint, Michigan 48503
Lansing, Michigan 48912
Livonia, Michigan 48154
Pontiac, Michigan 48341
Ypsilanti, Michigan 48197
Bemidji, Minnesota 56601
Saint Cloud, Minnesota 56303
Cape Girardeau, Missouri 63703
City of Saint Peters, Missouri 63376
Creve Coeur, Missouri 63141
Kansas City, Missouri 64108
Site Public Contact
816-404-4375
Kansas City, Missouri 64116
Site Public Contact
913-588-3671
Kansas City, Missouri 64154
Lee's Summit, Missouri 64064
St Louis, Missouri 63110
St Louis, Missouri 63128
St Louis, Missouri 63129
St Louis, Missouri 63136
St Louis, Missouri 63141
Site Public Contact
314-251-7066
Anaconda, Montana 59711
Billings, Montana 59101
Billings, Montana 59102
Site Public Contact
800-648-6274
Bozeman, Montana 59715
Great Falls, Montana 59405
Kalispell, Montana 59901
Missoula, Montana 59804
Basking Ridge, New Jersey 07920
Site Public Contact
212-639-7592
Cherry Hill, New Jersey 08002
Middletown, New Jersey 07748
Site Public Contact
212-639-7592
Montvale, New Jersey 07645
Site Public Contact
212-639-7592
Sewell, New Jersey 08080
Buffalo, New York 14263
Commack, New York 11725
Site Public Contact
212-639-7592
Cortland, New York 13045
Site Public Contact
607-756-3130
Harrison, New York 10604
Site Public Contact
212-639-7592
New York, New York 10029
New York, New York 10065
Site Public Contact
212-639-7592
Stony Brook, New York 11794
Site Public Contact
800-862-2215
Uniondale, New York 11553
Site Public Contact
212-639-7592
Durham, North Carolina 27705
Durham, North Carolina 27710
Site Public Contact
888-275-3853
Pinehurst, North Carolina 28374
Bismarck, North Dakota 58501
Fargo, North Dakota 58122
Fargo, North Dakota 58122
Columbus, Ohio 43210
Sylvania, Ohio 43560
Oklahoma City, Oklahoma 73104
Erie, Pennsylvania 16544
Site Public Contact
814-452-5000
Jefferson Hills, Pennsylvania 15025
Monroeville, Pennsylvania 15146
Site Public Contact
412-858-7746
Natrona Heights, Pennsylvania 15065
Philadelphia, Pennsylvania 19107
Philadelphia, Pennsylvania 19114
Pittsburgh, Pennsylvania 15212
Site Public Contact
877-284-2000
Pittsburgh, Pennsylvania 15224
Site Public Contact
412-578-5000
Sayre, Pennsylvania 18840
Site Public Contact
800-836-0388
Wexford, Pennsylvania 15090
Willow Grove, Pennsylvania 19090
Greenville, South Carolina 29601
Greenville, South Carolina 29607
Greenwood, South Carolina 29646
Rapid City, South Dakota 57701
Sioux Falls, South Dakota 57104
Sioux Falls, South Dakota 57117-5134
Dallas, Texas 75237
Dallas, Texas 75390
Fort Worth, Texas 76104
Richardson, Texas 75080
Murray, Utah 84107
Salt Lake City, Utah 84143
St. George, Utah 84770
Berlin Corners, Vermont 05602
Site Public Contact
802-225-5400
Burlington, Vermont 05401
Burlington, Vermont 05405
Fredericksburg, Virginia 22408
Richmond, Virginia 23235
Richmond, Virginia 23298
Tappahannock, Virginia 22560
Charleston, West Virginia 25304
Site Public Contact
304-388-9944
Appleton, Wisconsin 54911
Appleton, Wisconsin 54915
Brookfield, Wisconsin 53045
Chilton, Wisconsin 53014
Franklin, Wisconsin 53132
Green Bay, Wisconsin 54301
Green Bay, Wisconsin 54303
Madison, Wisconsin 53705
Site Public Contact
608-256-1901
Menomonee Falls, Wisconsin 53051
Site Public Contact
262-257-5100
Mequon, Wisconsin 53097
Milwaukee, Wisconsin 53211
Milwaukee, Wisconsin 53226
Site Public Contact
414-805-3666
New Berlin, Wisconsin 53151
Site Public Contact
414-805-0505
Oak Creek, Wisconsin 53154
Site Public Contact
414-805-0505
Oconto Falls, Wisconsin 54154
Oshkosh, Wisconsin 54904
Racine, Wisconsin 53405
Sheboygan, Wisconsin 53081
Sheboygan, Wisconsin 53081
Sturgeon Bay, Wisconsin 54235-1495
Wauwatosa, Wisconsin 53226
West Bend, Wisconsin 53095
Site Public Contact
414-805-0505
More Details
- Status
- Recruiting
- Sponsor
- Alliance for Clinical Trials in Oncology
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.