Randomized Phase II Trial on Short Term Darolutamide Concomitant to Radiation Therapy for Patients With Intermediate Unfavorable Risk Prostate Cancer

Overview

Randomized non-comparative phase II trial to assess the preliminary signs of antitumor activity of darolutamide plus radiation therapy in patients with unfavorable intermediate risk prostate cancer.

Description

Multicentric randomized non-comparative, open-label, phase II trial, based on signle-stage design, to assess the preliminary signs of antitumor activity of darolutamide plus radiation therapy in patients with unfavorable intermediate risk prostate cancer.

Patients satisfying eligibility criteria will be randomized according to 2 treatment modalities

• Arm A (experimental arm): combination of external beam radiotherapy (EBRT) and 6 months darolutamide.
• Arm B (standard arm): combination of external beam radiotherapy (EBRT) and 6 months ADT (androgen deprivation therapy)

Two patients randomized in arm A for one patient randomized in arm B.

Eligibility

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.