We Partner 4 Research

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

Recruiting Locations

Study Contact

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.