Intermittent Androgen Deprivation Therapy in the Era of AR Pathway Inhibitors

Trial Title: Intermittent Androgen Deprivation Therapy in the Era of AR Pathway Inhibitors

NCT ID: NCT05974774

Condition: Prostate Cancer

Conditions: Official terms:
Prostatic Neoplasms
Ascorbic Acid
Methyltestosterone
Androgens
Estrogens, Conjugated (USP)

Conditions: Keywords:
Metastatic hormone-naïve prostate cancer

Study type: Interventional

Study phase: Phase 3

Overall status: Not yet recruiting

Study design:

Allocation: Randomized

Intervention model: Parallel Assignment

Primary purpose: Treatment

Masking: None (Open Label)

Intervention:

Intervention type: Drug
Intervention name: iMAB
Description: no treatment until significant PSA increase as per treating physician at which point patient restarts ADT (LHRH agonist or antagonist) + ARPI (abiraterone or enzalutamide or apalutamide or darolutamide). Once PSA < 0.2 ng/mL, treatment stops again.
Arm group label: Arm B - intermittent treatment

Other name: intermittent maximum androgen blockade

Intervention type: Drug
Intervention name: cMAB
Description: LHRH agonist or antagonist + ARPI (abiraterone or enzalutamide or apalutamide or darolutamide)
Arm group label: Arm A - continuous treatment

Other name: continuous maximum androgen blockade

Summary: This study addresses the global topic of treatment optimization, i.e. achieving similar benefit while reducing the duration of treatment, hence hoping to decrease the burden of side-effects, improve quality-of life and reduce resource utilization. The primary goal of de-escalation is to investigate whether using an intermittent regime results in a similar OS to continuous treatment.

Detailed description: Prostate cancer is known to be dependent on testicular and adrenal androgens and the earliest identified treatments were the suppression of the body's production of testosterone. Then came the development of drugs able to block the androgen receptors that multiplied on the cancer cell membranes. The combination of these drugs presently approved by the EMA for first line treatment of mHNPC are understood to be given maximum androgen blockage and to be used until progression. All have been shown to positively impact overall survival. For patients, however, the consequences of continuous intensified MAB, and thereby testosterone suppression, have impacted their quality of life, especially in the form of fatigue, emotional distress, decrease of libido and loss of sexual function. This is in addition to toxicities linked to the mechanisms of these drugs which include cardiovascular diseases, cognitive effects and loss of bone mineral density. Treatment optimization is rarely addressed by clinical trials run for registration purposes. Toxicity is subsumed under efficacy and keeping the cancer at bay or controlled at any cost. Overall patient experience is not taken into account when determining what is an acceptable trade-off. Intermittent treatment or drug holiday are options to manage drug toxicities but longer off-treatment periods remain rare due to the fear of losing efficacy. Prostate cancer is an ideal setting to study the benefits of intermittent treatment as PSA levels have been shown to be a good indicator of cancer status. By holding androgen blockade after good PSA response, patients get the opportunity of seeing an improvement in their quality of life as testosterone levels slowly recover. The longer a patient stays off treatment, the more improvements to his overall wellbeing can be felt. Monitoring PSA levels provides an early signal to cancer regrowth and allows for the restart of MAB when it becomes necessary. While improving the patient's quality of life, there is as yet no indication as to the possible impact of this approach on overall survival. Alternating off/on treatment could delay both the start of the next line of treatment and the development of castration resistance but the absence of constant androgen suppression could also have the opposite effect and precipitate new alternatives to cancer cells testosterone dependence. This trial will randomize patients to either continue with their treatment as prescribed or to stop treatment until PSA levels indicate the necessity of restarting suppression. The latter group can stop treatment again when PSA levels reaches 0.2 ng/mL or lower. There is a need to investigate whether the benefit to patient's lives of holding long-term treatment will outweigh the risks of shortening overall survival. This trial is being done to allow both patients and their treating teams to have the data needed to make an informed decision on the best treatment approach.

Criteria for eligibility:
Criteria:
Inclusion Criteria: - Patient treated with ADT and an ARPI for mHNPC for 6-12 months and presenting with a PSA ≤ 0.2 ng/mL Note: Patient may have received docetaxel and radiotherapy of the prostate and metastases - Before patient 's enrolment, written informed consent must be given according to ICH/GCP, and national/local regulations Exclusion Criteria: - Patients with M1a on modern imaging technique (PET-Choline or -PSMA or Whole Body MRI) only for whom radiation therapy and 2 years of hormone therapy is recommended - Patients with a prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment for this trial - Patients who have received an investigational treatment as early intensification, which includes radical prostatectomy - Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be assessed and discussed with the patient before the enrolment in the trial

Gender: Male

Minimum age: 18 Years

Maximum age: 100 Years

Healthy volunteers: No

Start date: June 15, 2024

Completion date: December 15, 2030

Lead sponsor:
Agency: European Organisation for Research and Treatment of Cancer - EORTC
Agency class: Other

Collaborator:
Agency: Cancer Trials Ireland
Agency class: Other

Collaborator:
Agency: UNICANCER
Agency class: Other

Collaborator:
Agency: Spanish Oncology Genito-Urinary Group
Agency class: Other

Source: European Organisation for Research and Treatment of Cancer - EORTC

Record processing date: ClinicalTrials.gov processed this data on November 12, 2024

Source: ClinicalTrials.gov page: https://clinicaltrials.gov/ct2/show/NCT05974774