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

Summary

Objectives

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 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 through 30 months.
II. To compare quality of life as measured by FACT-P total outcome index and other subscales in the two arms at 6 and 24 months.
III. To compare pain severity and interference as measured by the Brief Pain Inventory Short Form (BPI-SF) in the two arms through 30 months.
IV. 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.
V. To compare rPFS, time to castration resistance, and OS between arms in patients with de novo metastatic disease having received primary directed radiation therapy.
VI. To determine rPFS, time to castration resistance, and OS correlation with PSA response at 6 weeks and 6 months.

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. If the patient has PSA progression, but the investigator deems patient is still deriving benefit from treatment, patients can continue therapy beyond PSA progression until radiographic progression. Additionally, patients undergo computed tomography (CT) scan or magnetic resonance imaging (MRI) and bone scan throughout the study. Patients may optionally undergo 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. If the patient has PSA progression, but the investigator deems patient is still deriving benefit from treatment, patients can continue therapy beyond PSA progression until radiographic progression. Additionally, patients undergo CT scan or MRI and bone scan throughout the study. Patients may optionally undergo blood sample collection throughout the study.

After completion of study treatment, patients are followed up every 6 months for up to 10 years from the time of randomization.