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

Prostate Cancer Clinical Trial

— DARIUS  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05346848
• Other study ID #: IB 2021-03
• Secondary ID: AFU-GETUG P15
• Status: Recruiting
• Phase: Phase 2
• Start date: February 24, 2023
• Est. completion date: February 2030

Study information

• Verified date: March 2023
• Source: Institut Bergonié
• Contact: Paul SARGOS, MD
• Phone: +33556333333
• Email: p.sargos[@]bordeaux.unicancer.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 62
• Est. completion date: February 2030
• Est. primary completion date: August 2025
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

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.

Related Conditions & MeSH terms

• Prostate Cancer
• Prostatic Neoplasms

Intervention

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 Organ at risk dose constraints according to RECORAD
• 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 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

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

Sponsors (2)

Lead Sponsor	Collaborator
Institut Bergonié	Bayer

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Assessment of efficacy in terms of 6-month biological response	Biological response is defined as a PSA concentration <=0.1ng/mL according to Phoenix's criteria	6 months after randomization
Secondary	Assessment of efficacy in terms of biological response at the end of darolutamide or ADT	Biological response is defined as a PSA concentration <=0.1ng/mL according to Phoenix's criteria	An expected average of 6 months
Secondary	2-month biological response	Biological response is defined as a PSA concentration <=0.1ng/mL according to Phoenix's criteria	2 months after randomization
Secondary	3-month biological response	Biological response is defined as a PSA concentration <=0.1ng/mL according to Phoenix's criteria	3 months after the end of radiotherapy
Secondary	6-month biological response	Biological response is defined as a PSA concentration <=0.1ng/mL according to Phoenix's criteria	6 months after the end of radiotherapy
Secondary	9-month biological response	Biological response is defined as a PSA concentration <=0.1ng/mL according to Phoenix's criteria	9 months after the end of radiotherapy
Secondary	2-year biological response	Biological response is defined as a PSA concentration <=0.1ng/mL according to Phoenix's criteria	2 years after randomization
Secondary	3-year biological response	Biological response is defined as a PSA concentration <=0.1ng/mL according to Phoenix's criteria	3 years after randomization
Secondary	5-year biological response	Biological response is defined as a PSA concentration <=0.1ng/mL according to Phoenix's criteria	5 years after randomization
Secondary	2-year biochemical progression-free survival (bPFS)	Biochemical progression-free survival is defined as the delay between the date of randomization and the date of biochemical disease progression or death, whichever comes first.	2 years
Secondary	3-year biochemical progression-free survival (bPFS)	Biochemical progression-free survival is defined as the delay between the date of randomization and the date of biochemical disease progression or death, whichever comes first.	3 years
Secondary	5-year biochemical progression-free survival (bPFS)	Biochemical progression-free survival is defined as the delay between the date of randomization and the date of biochemical disease progression or death, whichever comes first.	5 years
Secondary	2-year metastasis free survival (MFS)	Metastasis free survival is defined as the delay between the date of randomization and the date of metastasis diagnosis (imaging and/or biopsy)	2 years
Secondary	3-year metastasis free survival (MFS)	Metastasis free survival is defined as the delay between the date of randomization and the date of metastasis diagnosis (imaging and/or biopsy)	3 years
Secondary	5-year metastasis free survival (MFS)	Metastasis free survival is defined as the delay between the date of randomization and the date of metastasis diagnosis (imaging and/or biopsy)	5 years
Secondary	2-year disease free survival (DFS)	Disease free survival is defined as the delay between the date of randomization and the first of the following events: biological PSA progression defined as level higher than PSA nadir + 2ng/mL according to Phoenix's criteria ; progression (local, regional, distant) or death (any cause)	2 years
Secondary	3-year disease free survival (DFS)	Disease free survival is defined as the delay between the date of randomization and the first of the following events: biological PSA progression defined as level higher than PSA nadir + 2ng/mL according to Phoenix's criteria ; progression (local, regional, distant) or death (any cause)	3 years
Secondary	5-year disease free survival (DFS)	Disease free survival is defined as the delay between the date of randomization and the first of the following events: biological PSA progression defined as level higher than PSA nadir + 2ng/mL according to Phoenix's criteria ; progression (local, regional, distant) or death (any cause)	5 years
Secondary	2-year prostate cancer-specific survival (PCSS)	Prostate cancer-specific Survival is defined as the delay between the date of randomization and the date of prostate cancer-related death	2 years
Secondary	3-year prostate cancer-specific survival (PCSS)	Prostate cancer-specific Survival is defined as the delay between the date of randomization and the date of prostate cancer-related death	3 years
Secondary	5-year prostate cancer-specific survival (PCSS)	Prostate cancer-specific Survival is defined as the delay between the date of randomization and the date of prostate cancer-related death	5 years
Secondary	2-year overall survival (OS)	Overall survival is defined as the delay between the date of randomization and the date of death (all cause).	2 years
Secondary	3-year overall survival (OS)	Overall survival is defined as the delay between the date of randomization and the date of death (all cause).	3 years
Secondary	5-year overall survival (OS)	Overall survival is defined as the delay between the date of randomization and the date of death (all cause).	5 years
Secondary	Time to testosterone recovery	Time to testosterone recovery defined as the time from randomization to the time when serum of total testosterone level increases to above the lower limit of the normal range.	An expected average of 6 months
Secondary	Acute safety profile independently for each treatment strategy	Toxicity graded using the Common Terminology Criteria for Adverse Events version 5	3 months
Secondary	Late 2-year safety profile independently for each treatment strategy	Toxicity graded using the Common Terminology Criteria for Adverse Events version 5	2 years
Secondary	Late 3-year safety profile independently for each treatment strategy	Toxicity graded using the Common Terminology Criteria for Adverse Events version 5	3 years
Secondary	Late 5-year safety profile independently for each treatment strategy	Toxicity graded using the Common Terminology Criteria for Adverse Events version 5	5 years
Secondary	Assessment of quality of life	Quality of life will be assessed as per the EORTC QLQ-C30 questionnaire and prostate cancer module PR-25	Throughout the follow-up period, an expected average of 5 years
Secondary	Assessment of erectile dysfunction	Erectile dysfunction will be assessed as per IIEF5	Throughout the follow-up period, an expected average of 5 years
Secondary	Assessment of symptoms of benign prostatic hyperplasia	Symptoms of benign prostatic hyperplasia will be assessed as per IPSS	Throughout the follow-up period, an expected average of 5 years