ADT De-escalation in Selected High-Risk Prostate Cancer Patients (ADaPPt Trial) a GROUQ Led PCS Study (PCS XIV)

ADT De-escalation in Selected High-Risk Prostate Cancer Patients (ADaPPt Trial) a GROUQ Led PCS Study: A Phase III Trial Randomized Trial (PCS XIV)

High-risk prostate cancer is usually treated with a combination of radiation therapy and hormone therapy (ADT). Radiation destroys cancer cells, while ADT lowers testosterone, a hormone that prostate cancer cells need to grow. Together, these treatments help control the cancer.

ADT is usually given for 18 to 24 months, but it can cause side effects that may affect quality of life.

Some people with high-risk prostate cancer may do just as well with a shorter course of ADT. This study will identify people who are most likely to benefit from shorter treatment using imaging scans and tumor tests. It will then evaluate whether a shorter course of ADT works as well as the standard treatment while reducing long-term side effects.

Study Overview

• Status: Not yet recruiting
• Conditions: High Risk Prostate Cancer
• Intervention / Treatment: Drug: ZOLADEX 10.8 mg

• Study Type: Interventional
• Enrollment (Estimated): 600
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Mélanie Criqui, PhD; Phone Number: 26771 514340822; Email: melanie.criqui.ccomtl@ssss.gouv.qc.ca
• Study Contact Backup: Name: Paola Diego, Nurse; Phone Number: 24404 5143408222; Email: paola.diego.ccomtl@ssss.gouv.qc.ca

Study Locations

• Canada
  • Quebec
    • Montreal, Quebec, Canada, H3T 1E2
      • Jewish General Hospital
      • Principal Investigator: Tamim Niazi, MD
      • Contact: Paola Diego, Nurse; Phone Number: 24404 5143408222; Email: paola.diego.ccomtl@ssss.gouv.qc.ca
      • Contact: Melanie Criqui, PhD; Phone Number: 26771 5143408222; Email: melanie.criqui.ccomtl@ssss.gouv.qc.ca

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• • Able to understand and sign informed consent form (ICF);

  • Males aged ≥ 18 years;
  • Histologically confirmed adenocarcinoma of the prostate;

  • Participants with high-risk prostate cancer according to either of the following:

    a) High-risk disease - at least one of the following: i. T3a ii. Gleason 8 or less iii. PSA ≤ 30 ng/mL

iv. Gleason 9 (4+5) not more than 30% of the biopsy (e.g. a 10-needle biopsy can only have a maximum of 3 x 9 [4+5]);

• PTEN-proficient tumor confirmed by CLIA-certified immunohistochemistry (IHC);
• PSMA-PET within 90 days prior to randomization: negative for nodal or distant disease.
• Candidate for definitive radiation to prostate and pelvis;
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 or Karnofsky performance status of ≥70%;
• Testosterone ≥150 ng/dL or 5 nmol/L;
• Adequate hematologic, renal, liver function (Hemoglobin ≥10 g/dL, Absolute Neutrophil Count ≥1.5x10⁹/L, Platelets ≥100x10⁹/L);
• Judged to be medically fit for ADT and RT;
• Participants must be accessible for treatment and follow-up. Investigators must assure themselves the participants enrolled on this trial will be available for complete documentation of the treatment, adverse events, and follow-up.
• Sexually active patients, unless surgically sterile, must agree to use condoms as an effective barrier method and refrain from sperm donation during the study treatment and for 3 months after the end of the study treatment.

Exclusion Criteria:

• • Prior local or systemic therapy for prostate cancer (e.g. ADT, chemotherapy or novel Androgen Receptor Inhibitors [ARIs]);

  • PSMA-PET positive nodal or distant metastases;
  • PTEN loss or equivocal by IHC (at least more than 50%);
  • Evidence of nodal or distant metastases on conventional imaging;
  • Prior pelvic radiation or prostate surgery interfering with RT (except biopsy/TURP);
  • Life expectancy <5 years regardless of the prostate cancer;
  • Severe concurrent disease, infection, or co-morbidity that would make the patient inappropriate for enrollment (e.g. cardiovascular disease, hypertension, diabetes, etc);

  • Uncontrolled cardiovascular disease including:

    • Myocardial infarction within 6 months;
    • Unstable angina;
    • Congestive Heart Failure: New York Heart Association (NYHA) class III or IV;
    • Severe arrhythmia;
  • Active severe infection or immunocompromised;

  • Active second malignancy within 5 years with the exception of:

    • Non-melanoma skin cancer;
    • Chronic Lymphocytic Leukemia (CLL) that is stable and not actively treated;
  • Any condition compromising adherence to the protocol.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1 (experimental): 12 months of ADT + Radiotherapy; Zoladex is given for 12 months instead of 24	Drug: ZOLADEX 10.8 mg; The purpose of the study is to identify a subset of patient that may benefit to have a shorter Zoladex treatment (12 months vs 24 months)
Active Comparator: Arm 2 (standard of care): 24 months of ADT + Radiotherapy	Drug: ZOLADEX 10.8 mg; The purpose of the study is to identify a subset of patient that may benefit to have a shorter Zoladex treatment (12 months vs 24 months)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
5-year biochemical failure-free survival (bFFS)	Time from ADT initiation to time of first occurrence of biochemical failure (per Phoenix definition: PSA nadir + 2 ng/ml)	5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Metastasis-free survival	The first occurrence of distant progression or death from ADT initiation	5-8 years
Overall survival	The time from ADT initiation to the time of death from any cause.	5-8 years
Prostate cancer-specific mortality	The time from ADT initiation to the time of death from prostate cancer	5-8 years
8-year biochemical failure-free survival (bFFS)	Time from ADT initiation to time of first occurrence of biochemical failure (per Phoenix definition: PSA nadir + 2 ng/ml)	8 years
Toxicity - Acute	To determine acute toxicity due to treatment using the Common Terminology Criteria for Adverse Events (CTCAE) version 6.0	5 years
Toxicity - Late	To determine late toxicity due to treatment using the Common Terminology Criteria for Adverse Events (CTCAE) version 6.0	8 years
Quality of Life - General	Evaluate the impact of the treatment on the patient's quality of life using the FACT-P questionnaire	5-8 years
Quality of Life - Pain	Evaluate the impact of the treatment on the patient's quality of life using the Brief Pain Inventory (BPI) questionnaire	5-8 years
Quality of Life - Fatigue	Evaluate the impact of the treatment on the patient's quality of life using the Brief Fatigue Inventory (BFI) questionnaire	5-8 years
Testosterone Recuperation	Time from ADT completion to the return of serum-testosterone to non-castrate or normal baseline level	5-8 years

Collaborators and Investigators

• Sponsor: Dr. Tamim Niazi

Study record dates

Study Major Dates

• Study Start (Estimated): October 1, 2026
• Primary Completion (Estimated): October 1, 2035
• Study Completion (Estimated): October 1, 2040

Study Registration Dates

• First Submitted: July 22, 2026
• First Submitted That Met QC Criteria: August 18, 2026
• First Posted (Actual): August 20, 2026

Study Record Updates

• Last Update Posted (Actual): August 20, 2026
• Last Update Submitted That Met QC Criteria: August 18, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Keywords: prostate cancer; Zoladex; Jewish General Hospital
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Prostatic Diseases; Male Urogenital Diseases; Prostatic Neoplasms; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Pituitary Hormone-Releasing Hormones; Hypothalamic Hormones; Peptide Hormones; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins; Gonadotropin-Releasing Hormone; Goserelin
• Other Study ID Numbers: PCSXIV (AdaPPT)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No