Recurrence-directed therapy with or without 12 months of androgen-deprivation (ELIGARD) for radio-recurrent oligo-metastatic, hormone-sensitive prostate cancer

Phase II Randomized Trial of Recurrence-directed Therapy (RDT) With or Without Androgen-Deprivation Therapy (ADT) In Radio-recurrent Oligo-metastatic Hormone/Castrate Sensitive Prostate Cancer (romCSPC).

This will test whether adding 12 months of ELIGARD® (androgen-deprivation therapy) to recurrence-directed radiotherapy helps men with radio-recurrent oligo-metastatic, hormone-sensitive prostate cancer stay progression-free longer.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 162 (estimated)
• Ages: 18 Years and up
• Sex: Male
• Sponsor: Ontario Clinical Oncology Group (OCOG) (other)
• Drugs / interventions: chemotherapy
• Locations: 3 sites (Hamilton, Ontario and 2 other locations)
• Trial ID: NCT06654336 on ClinicalTrials.gov

What this trial studies

This is a multi-centre, open-label phase II randomized trial enrolling 162 men with prior radiotherapy-treated prostate adenocarcinoma who develop biochemical recurrence with up to five metastases. Participants are randomized 1:1 to receive recurrence-directed therapy (RDT) alone or RDT plus 12 months of ELIGARD® (leuprolide) as androgen-deprivation therapy. The primary outcome is progression-free survival, with secondary outcomes including development of castration-resistant disease, radiotherapy-related GU/GI toxicity, adverse events, initiation of further therapies, overall survival, and quality of life; follow-up visits occur every three months for 36 months. Imaging and clinical assessments will guide management and outcome measurements.

Who should consider this trial

Good fit: Men with prior localized prostate adenocarcinoma treated with definitive or salvage radiotherapy who have biochemical recurrence and no more than five metastatic sites on imaging, with lesions amenable to local treatment, are the intended candidates.

Not a fit: Patients with more widespread metastatic disease (>5 sites), castration-resistant prostate cancer, predominant non-adenocarcinoma histology, or lesions not suitable for local therapy are unlikely to benefit from this approach.

Why it matters

Potential benefit: If successful, adding 12 months of ADT to RDT could delay disease progression and postpone the need for additional systemic therapies.

How similar studies have performed: Smaller randomized and observational studies of metastasis-directed therapy with or without short-term ADT have suggested improved progression-free intervals, but definitive phase III evidence in this exact population is limited.

Eligibility criteria

Inclusion Criteria:

1. Previous biopsy-proven localized prostate adenocarcinoma (without predominant features of sarcomatoid, small cell or neuroendocrine carcinoma) treated with definitive or salvage radiotherapy ≥ 2 years or more before enrollment.
2. Recurrent Oligo-metastatic CSPC, M0 on conventional imaging (bone scan and CT scan of chest/abdomen/pelvis) with ≤ 5 metastases cumulative on all imaging, including MRI and PSMA-PET.

   Note: Patients with conventional imaging M1 oligometastatic CSPC, who have no more than 5 metastatic sites in all imaging modalities including MRI and PSMA-PET, will be accepted for study enrollment.
3. All sites of recurrent disease must be amenable to treatment with radiotherapy or surgery in the judgment of the investigator.
4. Biochemical recurrent prostate cancer with ONE of the following PSA recurrence definitions:

   1. After definitive radiotherapy (prostate in situ), with PSA ≥ nadir + 2ng/ml;
   2. After prostatectomy and adjuvant/salvage radiotherapy, with PSA ≥ nadir + 0.2ng/ml.

Exclusion Criteria:

1. Age \< 18.
2. ECOG Performance Status ≥3.
3. PSA ≥ 20 ng/ml.
4. Treatment with ADT within 2 years from study enrollment or treatment with any androgen receptor axis within 6 months from study enrollment.
5. Prior treatment with chemotherapy for prostate cancer or bilateral orchiectomy. Note: prior chemotherapy for a different type of cancer is allowed if the patient has been continuously disease-free for \> 3 years.
6. Intracranial or intrathecal metastasis.
7. Spinal cord compression, or spinal intramedullary metastasis.
8. Prior malignancy (except non metastatic, non- melanomatous skin cancer) unless disease free for \> 3 years.
9. Bilateral hip prosthesis, treated earlier with definitive prostate radiotherapy, who have evidence of local disease recurrence within the prostate and no option for salvage treatment with brachytherapy or surgery.
10. Previous documented hypersensitivity to ELIGARD® or other GnRH agonist analogs of components of such preparations.

Where this trial is running

Hamilton, Ontario and 2 other locations

• Juravinski Cancer Centre — Hamilton, Ontario, Canada (RECRUITING)
• The Ottawa Hospital Regional Cancer Centre — Ottawa, Ontario, Canada (NOT_YET_RECRUITING)
• Jewish General Hospital — Montreal, Quebec, Canada (RECRUITING)

Study contacts

• Principal investigator: Theos Tsakiridis, Dr. — McMaster University
• Study coordinator: Lisa Rudd-Scott, RN BScN

Conditions: Prostate Adenocarcinoma, Castration Sensitive Prostate Cancer, Prostate adenocarcinoma, Recurrent Oligo-metastatic Castration Sensitive Prostate CancerSPC, Andrigen Deprivation Therapy, Eligard, Recurrence Directed Therapy, Radiotherapy