NCT03899077

Radiotherapy Combined With a LHRH (Ant)Agonist Versus Apalutamide in Patients With Biochemical Recurrence After RP

A Phase II Study Comparing Salvage Radiotherapy in Combination With 6 Months of Androgen-deprivation Therapy Versus Anti-androgen Therapy With Apalutamide in Patients With Biochemical Progression After Radical Prostatectomy

• Status: Unknown
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 202 (estimated)
• Sponsor: Cancer Research Antwerp · Academic / Other
• Sex: Male
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This is a phase II randomized, open-label study comparing salvage radiotherapy in combination with 6 months of androgen-deprivation therapy (ADT) with LHRH agonist or antagonist (arm A) versus anti-androgen therapy (AAT) with apalutamide 240mg daily (arm B) in hormone-naïve patients with biochemical progression after radical prostatectomy. All subjects will receive salvage radiotherapy as standard of care and will be randomly assigned in a 1:1 ratio to receive either 6 months of androgen-deprivation therapy (ADT) with LHRH agonist or antagonist through 6 monthly, two 3-monthly or one 6-monthly injections (control arm) or 6 28-day cycles of apalutamide 240mg daily (interventional arm). The study will include a screening phase, treatment phase, and a post-treatment phase. The primary objective of the trial is to compare sexual function between the 2 groups based on the Expanded Prostate cancer Index Composite (EPIC)-26 sexual domain scores at 9 months after start of hormonal treatment.

Detailed description

After radical prostatectomy, around one third of patients will have biochemical progression. Salvage radiotherapy (SRT) is still potentially curative, but about 40-50% of patients will progress further. Recently, success rates of SRT were significantly improved through the use of concomitant anti-androgen (AAT) or androgen-deprivation (ADT) therapy. In RTOG 96-01, 2 years of bicalutamide 150 mg resulted in a 5% overall survival benefit at 12-years. In GETUG-AFU 16, 5-year progression-free survival was significantly improved when SRT was combined with 6 months of an LHRH agonist. Based on GETUG-AFU 16, most radiation oncologists now combine SRT with at least 6 months of ADT. However, ADT comes with several serious side-effects, both physical (cardiovascular, metabolic, musculoskeletal) and psychological (sexual, emotional and cognitive). It appears worthwile to look for alternatives in the form of AAT. In that respect, apalutamide, a potent competitive and purely antagonistic second-generation anti-androgen, is the ideal candidate. This trial is a phase II randomized, open-label study comparing salvage radiotherapy in combination with 6 months of ADT (arm A) versus AAT with apalutamide 240mg daily (arm B) in hormone-naïve patients with biochemical progression after radical prostatectomy. All subjects will receive salvage radiotherapy as standard of care and will be randomly assigned in a 1:1 ratio to receive either 6 months of ADT with LHRH agonist or antagonist through 6 monthly, two 3-monthly or one 6-monthly injections (control arm A) or 6 28-day cycles of apalutamide 240mg daily (interventional arm B). The study will include a screening phase, treatment phase, and a post-treatment phase. 1. Screening phase: allows for assessment of subject eligibility up to 35 days prior to randomization. 2. Treatment phase: includes the hormonal treatment for 6 months, to be started at the most 2 weeks after randomization and standard salvage radiotherapy. During the treatment phase, patients will have 3 study visits: 1. treatment initiation visit: first injection of LHRH (ant)agonist (arm A) or cycle 1, day 1 (C1D1) of apalutamide (arm B). 2. Concurrent with RT visit: if necessary (depending on product prescribed) injection of LHRH (ant)agonist (arm A) or cycle 4, day 1 (C4D1) of apalutamide (arm B). 3. End of treatment visit: at the end of the 6 months of hormonal therapy. 3. Post-treatment phase: will begin after a subject completes the treatment phase and the end of treatment visit and will continue until the primary endpoint is reached, i.e. the 9-months (3 months after end of treatment visit) EPIC-26 sexual domain score. The primary objective of the trial is to compare sexual function between the 2 groups based on the EPIC-26 sexual domain (0 - 100 scale, with higher scores representing better sexual function) at 9 months after start of hormonal treatment (primary endpoint). The following secondary endpoints will be explored: 1. Quality of life: assessed using EPIC-26 as well as the EORTC quality of life questionnaires C30 and PR25 as well as FACT-P. 2. Toxicity: will be assessed using the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. 3. Efficacy: prostate-specific antigen (PSA) response rates, defined as a decline from baseline in PSA level of 80% or greater, as well as PSA complete response rates, defined as a decline from baseline in PSA level of 90% or greater, will be prospectively collected at the 4 treatment visits. At this point in time, no study has directly compared apalutamide to LHRH agonists or antagonists in combination with SRT. This trial may be a preamble to the design of a registration trial in such patients or indeed patients with a intermediate and high-risk localized disease that are scheduled for EBRT or brachytherapy as radical treatment and also benefit from 6 months of hormonal treatment.

Conditions

• Cancer of Prostate

Interventions

Type	Name	Description
DRUG	Apalutamide	Apalutamide 240mg daily for 6 months (i.e. 6 28-day cycles); oral use
DRUG	Leuprorelin Acetate 45Mg Powder for Injection Suspension Vial	Leuprorelin acetate 45mg for 6 months; subcutaneous use
DRUG	Goserelin Acetate 10.8 MG Subcutaneous Implant	Goserelin acetate 10.8mg for 6 months; subcutaneous use
DRUG	Triptorelin Pamoate	Triptorelin pamoate 22.5mg for 6 months; intramuscular use
DRUG	Degarelix acetate	Degarelix acetate 80mg for 6 months; subcutaneous use

Timeline

• Start date: 2019-04-05
• Primary completion: 2025-08-01
• Completion: 2025-12-01
• First posted: 2019-04-02
• Last updated: 2024-02-07

Locations

9 sites across 1 country: Belgium