Testing the Addition of Docetaxel (Chemotherapy) to the Usual Treatment (Hormonal Therapy and Apalutamide) for Metastatic Prostate Cancer, ASPIRE Trial

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.

Eligibility Criteria

Interventions