Comparison of Short- and Long-term Androgen Deprivation Therapy with Salvage Radiotherapy in Prostate Cancer Recurrence: A Phase III Randomized Trial
- Trial ID
- 2024-517666-41-00
- Protocol
- URONCOR 06-24
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to compare the 5-year **metastasis-free survival** (MFS) rates in patients with **prostate cancer** who are treated with long-term versus short-term androgen deprivation therapy (ADT) in combination with salvage radiotherapy. This comparison is clinically relevant as it aims to determine the optimal duration of ADT that maximizes patient outcomes in terms of delaying metastasis, which is a critical factor in the management of prostate cancer following biochemical recurrence after prostatectomy.
Secondary objectives include comparing the two study arms in terms of:
- Biochemical-relapse free interval
- Pelvic progression-free survival
- Time to start of cytotoxic treatment
- Time to castration resistance
- Cancer-specific survival
- Overall survival
- Acute and late toxicity
Participants
The clinical trial focuses on **prostate cancer** patients, specifically targeting a male-only population. The study includes individuals who have undergone radical prostatectomy and are experiencing biochemical recurrence, defined by specific PSA levels. Participants are required to have a testosterone level greater than 150 ng/dL and an ECOG performance status of 0-1, indicating they are fully active or restricted in physically strenuous activity but ambulatory. The age range of participants is categorized as adults, and they must have a life expectancy of more than five years. The trial does not include a vulnerable population, and participants must provide signed informed consent. The sponsor has not provided information regarding the total number of participants. The trial aims to compare 5-year metastasis-free survival rates in patients treated with long- versus short-term androgen deprivation therapy in combination with salvage radiotherapy. Participants are selected based on specific inclusion criteria, including intermediate and high-risk classification according to established criteria, and must not have undergone lymph node dissection to be eligible. The trial does not consider female subjects, and no specific lifestyle considerations such as diet or physical activity are mentioned.
Plans and Procedures
The clinical trial is designed as a **randomized**, **controlled**, phase III study to evaluate the efficacy of short-term versus long-term androgen deprivation therapy (ADT) combined with salvage radiotherapy in patients with **prostate cancer** experiencing biochemical recurrence post-prostatectomy. The primary objective is to compare the 5-year metastasis-free survival (MFS) rates between the two treatment durations. The trial is expected to run from March 2023 to March 2026, with participant involvement lasting up to 24 months, depending on the treatment arm assigned.
Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as histologically-confirmed prostate cancer, biochemical recurrence, and a testosterone level greater than 150 ng/dL. Following randomization, participants will receive either short-term (6 months) or long-term (24 months) ADT, with follow-up visits scheduled to monitor treatment response and safety. These visits will include assessments of **PSA** levels, imaging tests if necessary, and evaluations of overall health status. The end-of-study visit will occur at the conclusion of the treatment period or upon early termination.
Early termination from the study may occur if participants experience significant adverse events, withdraw consent, or if the investigator deems it necessary for the participant's safety. The trial employs a double-blind methodology to ensure unbiased results, with neither participants nor investigators aware of the treatment allocation. The investigational medicinal products, including **goserelin acetate**, **leuprorelin acetate**, **bicalutamide**, and **triptorelin**, are administered in accordance with their marketing authorizations, ensuring no additional risk compared to standard clinical practice.
Treatment
The clinical trial involves the administration of several treatments for prostate cancer patients experiencing biochemical recurrence after prostatectomy. The **experimental medication** Zoladex 3.6 mg, containing the active substance **goserelin acetate**, is provided as an implant in a pre-filled syringe. This pharmaceutical form is designed for **subcutaneous injection**. The dosage is set at 3.6 mg, with a maximum treatment period of 24 months. The administration frequency is determined by the study protocol, and participant compliance is monitored throughout the trial. The product is of chemical origin and is manufactured by AstraZeneca Farmacéutica Spain, S.A.
Another **experimental medication** used in the trial is Eligard semestral 45 mg, which contains **leuprorelin acetate**. This treatment is provided as a powder and solvent for solution for injection. The pharmaceutical form is a solution for injection, with a dosage of 45 mg. The administration route is via injection, and the treatment period is also set at a maximum of 24 months. The product is of chemical origin and is produced by Recordati Industria Chimica e Farmaceutica S.P.A.
The trial also includes the use of Bicalutamida Aristo 50 mg, which contains the active substance **bicalutamide**. This medication is provided as a film-coated tablet for **oral use**. The dosage is 50 mg, with a maximum treatment period of 30 days. The product is of chemical origin and is manufactured by Aristo Pharma Iberia, S.L. This medication serves as an auxiliary treatment in the study.
Additionally, Decapeptyl semestral 22.5 mg, containing **triptorelin**, is utilized in the trial. This treatment is provided as a powder and solvent for prolonged-release suspension for injection. The pharmaceutical form is a prolonged-release suspension for injection, with a dosage of 22.5 mg. The administration route is via injection, and the treatment period is set at a maximum of 24 months. The product is of chemical origin and is produced by Ipsen Pharma SA.
Throughout the trial, participant compliance with the dosing schedules is closely monitored to ensure adherence to the study protocol. The trial aims to compare the efficacy of long-term versus short-term androgen deprivation therapy in combination with salvage radiotherapy, focusing on 5-year metastasis-free survival rates in prostate cancer patients.
Efficacy
Efficacy in this clinical trial will be assessed by evaluating the primary endpoint of 5-year **distant metastasis-free survival** (MFS) rates in patients with biochemically-recurrent prostate cancer after radical prostatectomy. The trial aims to compare the efficacy of long-term androgen deprivation therapy (ADT) for 24 months versus short-term ADT for 6 months, both in combination with salvage radiotherapy. The primary endpoint will be measured by tracking the absence of distant metastases over a 5-year period following treatment initiation.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Patients with histologically-confirmed prostate cancer treated with radical prostatectomy. Patients who have not undergone lymph node dissection are eligible for inclusion
- Biochemical recurrence after prostatectomy: BCR is defined as a PSA value ≥ 0.2 ng/mL, with at least one confirmatory PSA determination ≥ two weeks after the first test (the confirmatory PSA level must be higher than the initial value). Patients with Gleason 8-10, pT3b or R1 are eligible for inclusion in the trial with PSA ≥ 0.15 ng/mL; however, in patients with PSA > 0.4 ng/mL, imaging tests (conventional CT and bone scans or advanced imaging techniques such as PSMA or choline PET/CT) should be performed to check for metastases. In patients with PSA levels between 0.15 and 0.4 ng/mL, no further tests are required to check for distant metastases prior to inclusion.
- Intermediate and high-risk patients according to the classification criteria proposed by González San Segundo et al. (18) (Protocol page 8)
- Testosterone level > 150 ng/dL at inclusion
- ECOG 0-1
- Life expectancy > 5 years
- Signed informed consent
Exclusion Criteria
- Presence of pN1 disease in the original surgical specimen
- Presence of macroscopic disease on imaging tests. If the PSA at diagnosis is > 0.4 ng/mL, then imaging tests (CT and bone scan and/or PET/CT or body magnetic resonance imaging [MRI]) are required
- PSA <0.2 or <0.15 ng/mL (if Gleason score=10, pT3b, or R1 in the radical prostatectomy specimen).
- Previous pelvic radiotherapy
- Radiotherapy contraindicated
- Ongoing treatment with ADT or PSA-modulating drugs (e.g., finasteride, dutasteride, high dose steroids)
- Inability to understand the treatment protocol or sign informed consent
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Spain | Recruiting | 17 Mar 2023 | 534 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
Zoladex 3,6 mg implante en jeringa precargada | Test | IMPLANTE EN JERINGA PRECARGADA | SUBCUTANEOUS INJECTION | 3.6 | 24 | PRD395501 |
Decapeptyl semestral 22,5 mg polvo y disolvente para suspensión de liberación prolongada inyectable. | Test | POLVO Y DISOLVENTE PARA SUSPENSIÓN DE LIBERACIÓN PROLONGADA INYECTABLE | INJECTION | 22.5 | 24 | PRD390679 |
Eligard semestral 45 mg polvo y disolvente para solución inyectable. | Test | POLVO Y DISOLVENTE PARA SOLUCIÓN INYECTABLE | INJECTION | 45 | 24 | PRD9091001 |
Bicalutamida Aristo 50 mg comprimidos recubiertos con película EFG | Other | COMPRIMIDOS RECUBIERTOS CON PELÍCULA | ORAL USE | 50 | 30 | PRD7760965 |