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

Official title

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

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.

Detailed 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.

Interventions

• Drug Association of darolutamide and EBRT
  Darolutamide will be taken orally at a fixed dose of 600 mg twice daily (1200 mg), on a continuous basis, for a maximum of 6 months. Darolutamide will start at Day 1. \- External Beam Radiotherapy (EBRT) will start two months after treatment initiation. All patients will be treated with standard schedules: * 78 Gy with classical 2 Gy/fractions, 5 days/7 * Or 60 Gy with 3 Gy/fractions, 5 days/7 * Use of IMRT and IGRT is mandatory * Clinical Target Volume Definition according to GETUG Guidelines
• Drug Association of ADT and EBRT
  Treatment by Androgen Deprivation Therapy (ADT) will be prescribed as per market authorization and following investigator judgement. ADT treatment will consist on: * Either LH-RH agonist injection given every 3 months for 6 months, or once for 6 months, * Either LH-RH antagonist given monthly for 6 months External Beam Radiotherapy (EBRT) will start two months after treatment initiation. All patients will be treated by high dose irradiation in stereotactic conditions: * 78 Gy with classical 2

Primary outcome measures

• Assessment of efficacy in terms of 6-month biological response [Time frame: 6 months after randomization]

Secondary outcome measures (12)

• Assessment of efficacy in terms of biological response at the end of darolutamide or ADT [Time frame: An expected average of 6 months]
• 2-month biological response [Time frame: 2 months after randomization]
• 3-month biological response [Time frame: 3 months after the end of radiotherapy]
• 6-month biological response [Time frame: 6 months after the end of radiotherapy]
• 9-month biological response [Time frame: 9 months after the end of radiotherapy]
• 2-year biological response [Time frame: 2 years after randomization]
• 3-year biological response [Time frame: 3 years after randomization]
• 5-year biological response [Time frame: 5 years after randomization]
• 2-year biochemical progression-free survival (bPFS) [Time frame: 2 years]
• 3-year biochemical progression-free survival (bPFS) [Time frame: 3 years]
• 5-year biochemical progression-free survival (bPFS) [Time frame: 5 years]
• 2-year metastasis free survival (MFS) [Time frame: 2 years]

Eligibility criteria

Inclusion criteria

• Age ≥ 18,
• Histological diagnosis of prostate malignancy cancer
• 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),
• 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 .
• 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
• Patients must have a life expectancy of at least 5 years,
• Performance status ECOG ≤ 2,
• Patients without contra-indications to EBRT as per physician judgement,
• Patients with adequate organ function defined by all the following laboratory values
• Available archived paraffin-embedded tumor sample for research purpose,
• Patients with a social security in compliance with the french law,
• Voluntary signed and dated written informed consent prior to any study specific procedure,
• Men must agree to use an effective method of contraception throughout the treatment period and for one week after discontinuation of treatment.

Exclusion criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

France · 10 centers

• Sainte Catherine, Institut du Cancer Avignon-Provence — Avignon
• CHRU Besançon — Besançon
• Institut Bergonie — Bordeaux
• CHRU Brest - Hôpital Morvan — Brest
• Assitance Publique des Hôpitaux de Marseille - CHU La Timone — Marseille
• Hôpital de la Pitié Salpétrière — Paris
• CHP Saint-Grégoire — Saint-Grégoire
• Institut de Cancérologie de l'Ouest - Site René Gauducheau — Saint-Herblain
• … and 2 more centers

Identifiers

NCT: NCT05346848 · IB 2021-03 · AFU-GETUG P15

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗