Combining darolutamide with radiation therapy for prostate cancer treatment

A Randomized Non-comparative Phase II Multicentric Trial on Short Term Darolutamide (ODM-201) Concomitant to Radiation Therapy for Patients With Intermediate Unfavorable Risk Prostate Cancer

This study is testing if adding darolutamide to radiation therapy can help men with intermediate risk prostate cancer do better than just using standard hormone therapy with radiation.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 62 (estimated)
• Ages: 18 Years and up
• Sex: Male
• Sponsor: Institut Bergonié (other)
• Drugs / interventions: chemotherapy, radiation
• Locations: 10 sites (Avignon and 9 other locations)
• Trial ID: NCT05346848 on ClinicalTrials.gov

What this trial studies

This phase II trial evaluates the effectiveness of darolutamide in combination with external beam radiation therapy (EBRT) for patients diagnosed with unfavorable intermediate risk prostate cancer. Participants will be randomly assigned to receive either darolutamide with EBRT or standard androgen deprivation therapy (ADT) with EBRT. The study aims to assess preliminary signs of antitumor activity and improve treatment outcomes for this patient population. The trial is multicentric and open-label, allowing for a diverse participant pool.

Who should consider this trial

Good fit: Ideal candidates are adult males aged 18 and older with a histological diagnosis of prostate cancer classified as unfavorable intermediate risk.

Not a fit: Patients with metastatic prostate cancer or those who do not meet the specific criteria for unfavorable intermediate risk may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could enhance treatment efficacy and improve outcomes for patients with unfavorable intermediate risk prostate cancer.

How similar studies have performed: Previous studies have shown promise in combining targeted therapies with radiation, suggesting potential for success in this novel approach.

Eligibility criteria

Inclusion Criteria:

1. Age ≥ 18,
2. Histological diagnosis of prostate malignancy cancer
3. Cancer without loco-regional or distant metastasis (tumor assessment must comprise at least Pelvic MRI AND thoraco-abdomino-pelvic contrast-enhanced CT-Scan AND Bone Scintigraphy. (Note that additional assessment by PET-Scan is allowed as per investigator judgement),
4. Unfavorable intermediate risk prostate cancer diagnosis defined by the NCCN Guidelines.

   One of the following criteria is sufficient to define an unfavorable intermediate risk prostate cancer:
   * Gleason = 7 (4+3)
   * ≥ 50% of thecore of biopsies need to be positive for adenocarcinoma

   If these criteria are not being identified, two or three of the following criteria are necessary to define unfavorable intermediate risk prostate cancer:
   * PSA value between 10-20 ng/ml
   * Gleason 7 (3+4) or 6
   * T2b (clinical or radiological) Note: patients with iT3a can be included only if gleason score is 6 and PSA less than 20 .
5. Patients newly diagnosed with an unfavorable intermediate risk prostate cancer according to the protocol criteria or previously diagnosed with low risk (Gleason score \< 6, clinical stage \< T2a, and PSA\< 10) prostate cancer progressing to eligible risk disease according to the protocol criteria within 30 days before registration
6. Patients must have a life expectancy of at least 5 years,
7. Performance status ECOG ≤ 2,
8. Patients without contra-indications to EBRT as per physician judgement,
9. Patients with adequate organ function defined by all the following laboratory values
10. Available archived paraffin-embedded tumor sample for research purpose,
11. Patients with a social security in compliance with the french law,
12. Voluntary signed and dated written informed consent prior to any study specific procedure,
13. Men must agree to use an effective method of contraception throughout the treatment period and for one week after discontinuation of treatment.

Exclusion Criteria:

1. Stage T3b-T4 prostate cancer by clinical examination or radiologic evaluation,
2. Patients with Gleason score ≥8,
3. Patients with PSA \>20 ng/ml,
4. Presence of loco-regional or distant metastasis,
5. Contra-indications to MRI and to contrast-enhanced CT-scan,
6. Hypogonadism or severe androgen deficiency as defined by screening serum testosterone less than 50 ng/dL or below the normal range for the institution.
7. Previous prostate cancer treated by androgen deprivation, chemotherapy, surgery, or radiotherapy,
8. Patients with previous orchiectomy
9. Patients actively receiving or having received within 6 months prior enrollment any concurrent androgens, anti-androgens, estrogens, or progestational agents,
10. Patients having received ketoconazole, finasteride or dutasteride within 30 days of inclusion,
11. Previous and current malignancies other than prostate cancer within the last 5 years with the exception of adequately treated basal cell or squamous cell carcinoma of the skin, acute lymphoblastic leukemia, non-muscle invasive bladder cancer,
12. Severe or uncontrolled medical conditions (i.e. uncontrolled diabetes, active or uncontrolled infection),
13. History of cerebrovascular accident (within the last 6 months)
14. Impaired cardiac function as defined in the Protocol
15. Uncontrolled hypertension
16. Impairment of gastrointestinal function or GI disease that may significantly alter the absorption of study drug,
17. Major surgery within 4 weeks prior enrolment except pelvic lymph-nodes dissection,
18. Known hypersensitivity to any involved study drug or of its formulation components, to natural gonadotrophin releasing hormone or its analogues
19. Galactose intolerance, total lactase deficiency or glucose-galactose malabsorption syndrome
20. Men who are not using an effective method of contraception as previously described
21. Use of herbal or alternative remedies that may affect hormonal status such as Prostasol or PC-SPES,
22. History of non-compliance to medical regimens or inability to grant consent,
23. Patient unable to follow and comply with the study procedures because of any geographical, social or psychpsychological reasons,
24. Individuals under judicial protection or deprived of liberty.
25. Inability to swallow or to give subcutaneous or intramuscular injections.

Where this trial is running

Avignon and 9 other locations

• Sainte Catherine, Institut du Cancer Avignon-Provence — Avignon, France (NOT_YET_RECRUITING)
• CHRU Besançon — Besançon, France (NOT_YET_RECRUITING)
• Institut Bergonie — Bordeaux, France (RECRUITING)
• CHRU Brest - Hôpital Morvan — Brest, France (NOT_YET_RECRUITING)
• Assitance Publique des Hôpitaux de Marseille - CHU La Timone — Marseille, France (NOT_YET_RECRUITING)
• Hôpital de la Pitié Salpétrière — Paris, France (NOT_YET_RECRUITING)
• CHP Saint-Grégoire — Saint-Grégoire, France (NOT_YET_RECRUITING)
• Institut de Cancérologie de l'Ouest - Site René Gauducheau — Saint-Herblain, France (NOT_YET_RECRUITING)
• IUCT Oncopôle — Toulouse, France (NOT_YET_RECRUITING)
• Clinique Pasteur — Toulouse, France (NOT_YET_RECRUITING)

Study contacts

• Study coordinator: Paul SARGOS, MD

Conditions: Prostate Cancer, unfavorable intermdiate risk prostate cancer, androgen deprivation therapy, radiation therapy