Randomized Phase II Trial on Short Term Darolutamide Concomitant to Radiation Therapy for Patients With Intermediate Unfavorable Risk Prostate Cancer
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
Institut Bergonié
62 participants
Feb 24, 2023
INTERVENTIONAL
Conditions
Summary
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.
Eligibility
Inclusion Criteria20
- 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 Criteria25
- 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.
Interventions
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 * Organ at risk dose constraints according to RECORAD
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 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 * Organ at risk dose constraints according to RECORAD
Locations(10)
View Full Details on ClinicalTrials.gov
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NCT05346848