Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

All Conditions

Symptoms and General Pathology

Prostatic Neoplasms

Neoplasm Metastasis

Prostatic Neoplasms, Castration-Resistant

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

All Drugs and Chemicals

Androgens

Hormones

Hormone Antagonists

2 tablets of 300 mg twice daily (=1200 mg/day) up to 5 years from randomisation

Darolutamide 300 mg

Over one week,30 Gy in 3 fractions of 10 Gy

Stereotactic body radiation therapy

Continuous ADT during the study course. The choice of ADT is left to the discretion of the investigator.

Androgen deprivation therapy

Ronan FLIPPOT

David PASQUIER

In earlier stages of prostate cancer, male sexual hormones (androgens) stimulate the growth of cancer cells. Castration-resistant prostate cancer (CRPC) means that the prostate cancer continued to grow despite patients are taking hormone therapy to control the disease. One of the standard treatments for these patients is so-called 'new generation' hormonal therapy. These hormone therapies include apalutamide, enzalutamide, or darolutamide. They work by blocking androgen receptors that play an important role in the growth of prostate cancer.

In the case of oligometastatic CRPC, the cancer has gone beyond the prostate and has spread to other organs in the body (metastases), but these metastases remain limited in number.

An early detection of the oligometastatic CRPC and appropriate treatment may prolong survival in these patients.

The treatment proposed as part of this research is a combination of oral darolutamide, approved in Europe to treat patients with CRPC who do not have metastasis visible on CT-scan or bone scintigraphy (but visible with positron emission tomography-scan (PET-Scan), a more precise imaging technique) with stereotactic body radiotherapy (SBRT), a new radiotherapy technique guided by very high precision medical imaging. This method makes it possible to better target cancer cells while preserving neighboring healthy organs.

The principal objective of this trial is to evaluate the efficacy of the combination of SBRT with darolutamide, compared to darolutamide.

PEACE 8 is a phase III open-label, randomised (patients are randomly assigned to treatment), international, multicentre trial, evaluating the benefit of adding SBRT to darolutamide for treating patients with oligometastatic CRPC.

Eligible patients will be randomised into either an experimental group receiving darolutamide + SBRT or a control group receiving darolutamide. In both arms, all patients will receive continuous castration (ADT) during the trial course.

Patients' participation in the trial will not exceed 60 months after randomisation, including a maximum treatment duration of 60 months and follow-up up to 60 months after randomisation.

After signing the consent form, patients will enter the pre-inclusion period (before the start of treatment), during which the investigator will carried out all the tests required to assess their eligibility, including demographic data collection, tumour evaluation, and clinical and biological assessments.

Patients will receive doralutamide until disease progression or unacceptable toxicity for a maximum of 5 years after the start of treatment.

To receive treatment, the patient will need to go to hospital, where, at each visit, the medical team will conduct medical examinations before administering the treatment to assess the patient's general state of health and tolerance to the treatment.

Eligible patients will be randomly allocated in a 1:1 ratio to either the:

* Control arm: ADT + darolutamide.
* Experimental arm: ADT + darolutamide + SBRT.

Treatment With Darolutamide +/- Radiation Therapy for Patients With a Castration Resistant Cancer and Metastases Detected by Functional Imaging

Combination of Darolutamide and Stereotactic Body Radiation Therapy in Patients With Castration Resistant Prostate Cancer and Oligometastases on Functional Imaging

The radiographic Progression-free survival is defined as the time interval between the randomisation and radiographic disease progression with conventional imaging (CT-scan or bone-scan), or death due to any cause, whichever occurs first.

The time to treatment failure is defined as the time interval between randomisation and the discontinuation of darolutamide, irrespective of the reason for discontinuation.

The overall survival is the length of time from randomization that patients enrolled in the study are still alive.

The prostate cancer-specific survival is defined as the time interval between randomisation and the date of death due to prostate cancer.

The time to PSA progression is defined as the time interval between the date of randomisation and the date of PSA progression. PSA progression is defined, in accordance with the PCWG3 guidelines which retained the PCWG2 definition (2007 guidelines).

The biochemical response rate is defined as the proportion of patients with a decrease in PSA levels of ≥50% from baseline levels.

The time to next symptomatic skeletal event is defined as the time interval from randomisation until the first occurrence of a symptomatic fracture, bone radiation (for pain or neurological complication), bone surgery (for pain or neurological complication), or spinal cord compression.

The time to pain progression is defined as the time interval from randomisation until the first occurrence of any of the following:

* Increase of ≥2 points, from baseline, in question 3 of the Brief Pain Inventory-Short Form (BPI-SF) questionnaire (item related to the worst pain in the last 24 hours).
* Initiation of opioid treatment for cancer pain.
* Increase in the use of opioid treatment of ≥30% in terms of frequency of use or cumulative dose.

The National Cancer Institute-Common Terminology Criteria for Adverse Events version 5 (NCI-CTCAE v5) is widely accepted in the community of oncology research as the leading rating scale for adverse events. This scale, divided into 5 grades (1 = "mild", 2 = "moderate", 3 = "severe", 4 = "life-threatening", and 5 = "death") determined by the investigator, will make it possible to assess the severity of the disorders.

The FACT-P is a self-assessment questionnaire to estimate the health-related quality of life in men with prostate cancer. This questionnaire, composed of 39 items consists of four subscales: Physical Well-Being (7 items), Social/Family Well-Being (7 items), Emotional Well-Being (6 items), Functional Well-Being (7 items), and prostate cancer subscale (12 items). Subscales are rated on 5-point Likert-type scale (from 0 = "Not at all" to 4 = "Very much"). For all subscales, a higher score represents better quality of life.

The Brief Pain Inventory (BPI) questionnaire rapidly assesses the severity of pain and its impact on functioning. This self-report questionnaire includes:

* A body schema
* The maximum pain, lowest pain, usual pain within the last 15 days (Numeric rating scales (NRS) 0 to 10)
* Description of current analgesic treatment,
* An assessment of relief by a percentage scale (0-100%), Assessment of the impact of pain on: mood, relationships with others, walking, sleep, work, happiness the joy - of living, recreation, activities in general (digital scales, rating from 0 \[normal\] to 10 \[no activity\]).

Bayer

UNICANCER

Lymphatic Metastasis

Neoplastic Processes

Arm A: ADT + Intensity-Modulated Image-Guided Radiation Therapy + Darolutamide ADT will be associated with LHRH agonists or antagonists for 24 months4. Darolutamide regimen will be of 2 tablets of 300 mg orally twice daily for 24 months.

Arm B: ADT + Intensity-Modulated Image-Guided Radiation Therapy + Placebo of Darolutamide

ADT will be associated with LHRH agonists or antagonists for 24 months4. Darolutamide regimen will be of 2 tablets of 300 mg orally twice daily for 24 months.

Darolutamide regimen will be of 2 tablets of 300 mg orally twice daily for 24 months.

Placebo of Darolutamide regimen will be of 2 tablets of 300 mg orally twice daily for 24 months.

Placebo of Darolutamide

Ishak Senouci

Pierre COMBE, MD

Prospective, multicenter, comparative, randomized placebo-controlled Phase III trial - patients with hormone-naïve prostate cancer and pelvic lymph nodes metastases

Standard of care for patients with prostate cancer (PC) with pelvic lymph nodes metastases is radiotherapy (RT) with long-term androgen deprivation therapy (ADT). . Darolutamide improves survival in men with castration-refractory non metastatic prostate cancer. We hypothesize that adding Darolutamide to ADT and RT could improve FFS for these high-risk patients.

Evaluation of dAroLutamide Addition to anDrogen Deprivation Therapy and radIatioN Therapy in Newly Diagnosed Prostate Cancer With Pelvic Lymph Nodes Metastases

The failure-free survival is defined as the time from the date of randomization to clinical (new cancer-related symptoms), biochemical (PSA rising) or radiological (local relapse or new metastases) progression, death, end of 3-year follow-up period or lost to follow-up, whichever occurs first.

To evaluate the metastasis-free survival rates

To evaluate the progression free survival rates

PSA response is defined by the rate of patients having a decrease of \> 50% of their PSA level, as measured every 3 months from the date of randomization to the date of a documented biochemical relapse.

Overall survival is defined as the time from the date of randomization to the date of documented death from any cause, end of 3-year follow-up period or lost to follow-up, whichever occurs first

Cancer-specific survival is defined as the time from the date of randomization to the date of documented death from prostate cancer or complication from the treatment, end of 3-year follow-up period or lost to follow-up, whichever occurs first

Time to pain progression is defined as the time from the date of randomization to the date of documented pain, end of 3-year follow-up period or lost to follow-up, whichever occurs first

To evaluate toxicities (CTCAE v5.0) due to treatements

Quality of life will be assessed using self-administered questionnaires (European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire : EORTC QLQ-C30 v2)

Quality of life will be assessed using self-administered questionnaires (European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire : EORC QLQ-PR25 V3)

Quality of life will be assessed using self-administered questionnaires (European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire : EORTC QLQ-PR253) by patients

Association Pour La Recherche des Thérapeutiques Innovantes en Cancérologie

Rare Diseases

Kennedy Disease

Antineoplastic Agents

Docetaxel

Placebo

Soazig N Ficher

Isabelle Rieger

Marco GIZZI, MD

Emmanuel SERONT, MD

Vincent VANHAUDENARDE, MD

Nicolas WHENHAM, MD

Werner HILGERS, MD

Louis FRANCOIS, MD

Antoine THIERY VUILLEMIN, MD

Guihem ROUBAUD, MD

Ali HASBINI, MD

Florence JOLY, MD

Mélanie TADJ LESAGE, MD

Hakim MAHAMMEDI, MD

Christophe TOURNIGAND

Sylvain LADOIRE, MD

Mathieu LARAMAS, MD

Frank PRIOU, MD

Benoît SEUWIN, MD

Antonin BROYELLE, MD

Sabrina FALKOWSKI, MD

Caroline CHENEAU, MD

Aude FLECHON, MD

Gwenaelle GRAVIS, MD

Philippe Ronchin, MD

Delphine BORCHIELLINI, MD

Nadine HOUEDE, MD

Zahra Castel Ajgal, MD

Camille SERRATE, MD

Hélène GAUTHIER, MD

Stéphane OUDARD, MD

Ahmed KHALIL, MD

Sophie TARTAS, MD

Sheik EMAMBUX, MD

Marie LOUVEL, MD

Friederike SCHLURMANN, MD

Jean-Christophe EYMARD, MD

Laurence Crouzet, MD

Guillermo REYES-ORTEGA, MD

Xavier ARTIGNAN, MD

Carole HELISSEY, MD

Pierre Cornillon, MD

Aline GUILLOT, MD

Louis-Marie DOURTHE, MD

Philippe BARTHELEMY, MD

Raffaele RATTA, MD

Xavier TCHIKNAVORIAN, MD

Loic MOUREY, MD

Igor LATORZEFF, MD

Claude LINASSIER, MD

Vincent MASSARD, MD

Karim FIZAZI, MD

Ray MCDERMOTT, MD

John McCAFFREY, MD

Albert FONT, MD

Begona MELLADO, MD

Alejo RODRIGUEZ VIDAL, MD

Joan CARLES, MD

Nuria SALA, MD

Juan Francisco RODRIGUEZ MORENO, MD

Daniel CASTELLANO, MD

Mariona FIGOLS, MD

Miguel RAMIREZ BACKHAUS, MD

Giulia Baciarello, MD

Karim Fizazi, MD

This is a Phase III, international, multicentre, randomised, double-blinded placebo controlled trial, evaluating the efficacy and safety of ADT +/- darolutamide in castration-naïve de novo metastatic prostate cancer patients with vulnerable functional ability who have not elected for docetaxel or other androgen receptor pathway inhibitors.

This is a Phase III, international, multicentre, randomised, double-blinded placebo controlled trial, evaluating the efficacy and safety of ADT +/- darolutamide in castration-naïve de novo metastatic prostate cancer patients with vulnerable functional ability who have not elected for docetaxel or other androgen receptor pathway inhibitors. The study plans to enroll 300 patients who will be randomized (1:1) to receive either: (i) Experimental arm: ADT + darolutamide 600 mg po bid, or (ii) Control arm: ADT + placebo po bid. Response to treatment will be assessed according to the Prostate Cancer Clinical Trials Working Group 3 (PCWG3) criteria (Scher, 2016). Treatment will be continued until radiographic disease progression. Treatment may also be terminated at the initiative of either the patient or the investigator for any reason that would be beneficial to the patient, including: unacceptable toxicity, intercurrent conditions that preclude continuation of treatment, or patient request. Following treatment discontinuation patients will enter the follow-up period and will be monitored for up to 10 years with regards to survival status, subsequent antineoplastic treatments and the status of ongoing adverse events (AEs) and/or new investigational product related AEs.

Phase III, international, multicenter, randomized

ADT +/- Darolutamide in de Novo Metastatic Prostate Cancer Patients With Vulnerable Functional Ability (PEACE6-Vulnerable)

A Double-blind Randomised Phase III Trial Evaluating the Efficacy of ADT +/- Darolutamide in de Novo Metastatic Prostate Cancer Patients With Vulnerable Functional Ability and Not Elected for Docetaxel or Androgen Receptor Targeted Agents

IPD can be shared upon request to the sponsor

Time from randomisation to radiographic progression according to the Prostate Cancer Working Group 3 (PCWG3) criteria or death, whichever occurs first

Time from randomisation to onset of castrate resistant prostate cancer (CRPC) according to PCWG3 criteria, or death, whichever occurs first

Time from randomisation to first occurrence of any one of the following:

(i) Cancer pain deterioration (2-point deterioration from baseline according to the Brief Pain Inventory - Short Form \[BPI-SF\] questionnaire; initiation of opioid therapy, or a ≥30% increase in opiate use) (ii) Any deterioration of physical function measured using the 4-IADL assessment tools (Lawton, 1969) (iii) A deterioration in ECOG performance status of at least 2 points from baseline (iv) Death from any cause.

Time from randomisation to the time of death from any cause

The National Cancer Institute-Common Terminology Criteria for Adverse Events version 5 (NCI-CTCAE v5) is widely accepted in the community of oncology research as the leading rating scale for adverse events. This scale, divided into 5 grades (1 = "mild", 2 = "moderate", 3 = "severe", 4 = "life-threatening", and 5 = "death") determined by the investigator, will make it possible to assess the severity of the disorders

Time from randomisation to first increase from baseline of greater or equal to 8 points in the urinary symptom scale/score (PRURI) measured using the prostate cancer module of the EORTC quality of life questionnaire (EORTC-QLQ-PR25).

This EORTC prostate cancer specific questionnaire is intended to supplement the QLQ-C30. The prostate cancer module is a 25-item questionnaire designed for use among patients with localized and metastatic prostate cancer. It includes subscales assessing urinary symptoms (9 items), bowel symptoms (4 items), treatment-related symptoms (6 items) and sexual functioning (6 items). Using a 4-point Likert scale (1 = "not at all", 2 = "a little", 3 = "quite a bit", and 4 = "very much"), patients indicate the degree to which they have experienced symptoms.

Time from randomisation until first occurrence of one of the following: a symptomatic fracture, radiation or surgery to bone or a spinal cord compression

Defined according to PCWG3 criteria as PSA ≤ 0.2 ng/ml

Time from randomisation to the date of death due to prostate cancer (deaths due to other causes will be censored)

Time from randomisation to the date of initiation of any SACT for CRPC, following initiation of the study treatment

Time from the date of initiation of a second SACT for CRPC to radiographic progression or death, whichever occurs first.

Time from the date of initiation of a second SACT for CRPC to death

Time from randomisation to second objective disease progression, or death from any cause, whichever first

Evaluated using the G-CODE (Paillaud, 2018), a core set of commonly used tools/items for geriatric assessment which has been validated for the collection of geriatric data in clinical cancer trials of older adults, enabling comparison across trials. The tools/items proposed in G-CODE are:

(i) Social assessment: living alone or support requested to stay at home; (ii) Functional autonomy: Activities of Daily Living (ADL) questionnaire and short instrumental ADL questionnaire (4-IADL); (iii) Mobility: Timed Up and Go test; (iv) Nutrition: weight loss during the past 6 months and body mass index; (v) Cognition: Mini-Cog test; (vi) Mood: mini-Geriatric Depression Scale; (vii) Comorbidity: updated Charlson Comorbidity Index.

Defined as the first decline in the HRQoL score from baseline equal to or greater than the minimally important difference (MID; a measure of clinical significance) defined as half the standard deviation of the baseline value for each subscale. The prostate cancer module QLQ-PR25 is a 25-item questionnaire designed for use among patients with localized and metastatic prostate cancer. It includes subscales assessing urinary symptoms (9 items), bowel symptoms (4 items), treatment-related symptoms (6 items) and sexual functioning (6 items). Using a 4-point Likert scale (1 = "not at all", 2 = "a little", 3 = "quite a bit", and 4 = "very much"), patients indicate the degree to which they have experienced symptoms.

Developed by the EORTC, this self-reported questionnaire assesses the health-related quality of life of cancer patients in clinical trials.

The questionnaire includes five functional scales (physical, everyday activity, cognitive, emotional, and social), three symptom scales (fatigue, pain, nausea and vomiting), a health/quality of life overall scale, and a number of additional elements assessing common symptoms (including dyspnea, loss of appetite, insomnia, constipation, and diarrhea), as well as, the perceived financial impact of the disease.

All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level.

This EORTC prostate cancer specific questionnaire is intended to supplement the QLQ-C30.

The prostate cancer module is a 25-item questionnaire designed for use among patients with localized and metastatic prostate cancer. It includes subscales assessing urinary symptoms (9 items), bowel symptoms (4 items), treatment-related symptoms (6 items) and sexual functioning (6 items). Using a 4-point Likert scale (1 = "not at all", 2 = "a little", 3 = "quite a bit", and 4 = "very much"), patients indicate the degree to which they have experienced symptoms.

The Brief Pain Inventory is a self reporting tool to assess the severity of pain and the impact of pain on daily functions in patients with chronically painful diseases or conditions such as cancer, osteoarthritis and low back pain, or with pain from acute conditions such as postoperative pain. The Short Form of the questionnaire (BPI-SF) has been specifically developed for clinical trials.

Testosterone

Pathological response rate after radical prostatectomy with dalotamide combined with androgen deprivation therapy (ADT) in neoadjuvant therapy for surgically resectable high-risk or very high-risk prostate cancer.

Duration of treatment: 28-day cycle of darotamide treatment and 6 cycles of neoadjuvant therapy. ADT treatment continued during neoadjuvant therapy and was discontinued after surgery.

Adjusted dosing: When the serum testosterone concentration cannot be maintained at \<50 ng/dL, the dose and type of ADT can be adjusted. Investigators can adjust the dose of darostatide according to the situation.

600 mg (300 mg × 2 tablets) twice daily with meals, equivalent to a total daily dose of 1200 mg.

The ADT regimen used by each patient will be determined by the investigator, and the dose and frequency of administration will be consistent with the prescribing information.

Hongqian Guo, Phd

Shun Zhang, Phd

Hongqian Guo, PhD

This trial aims to evaluate the efficacy and safety of neoadjuvant therapy with Darolutamide combined with Androgen-Deprivation Therapy in High-risk/Very high-risk localized prostate cancer. This trial is A prospective, single-arm, multicenter clinical trial. Treatment cycle is 24 weeks,

High risk prostate cancer (PCa) had worse outcomes on radical treatment results, short-time oncological results, even cancer-specific survival, than those low or mediate risk PCa. Neoadjuvant treatment before radical prostatectomy had been proven to get some benefits on peri-operation results, especially on reduction of tumor volume and minimization of biochemical recurrence. This study will evaluate the efficacy and safety of androgen deprivation therapy (ADT) with Darolutamide in neoadjuvant therapy for surgically resectable high-risk or very high-risk PCa.

Efficacy and Safety of Darolutamide Combined With ADT in High-risk/Very High-risk Localized Prostate Cancer

Medical Ethics Committee of Nanjing Drum Tower Hospital Affiliated to Medical School of Nanjing University

Defined by Functional Assessment of Cancer Therapy-Prostate (FACT-P) questionnaire

Defined by worst pain item based on BPI-SF questionnaire.

Pathological Response Rate is defined as the pCR(Pathologic Complete Response Rate) or MRD (Proportion of Subjects With Minimal Residual Disease) Pathologic Complete Response Rate is defined as the proportion of subjects with no morphologically recognizable cancer cell in tumor specimens after radical prostatectomy.

Proportion of Subjects With Minimal Residual Disease is defined as the proportion of subjects that have residual tumors with maximum diameter of 5 mm or less after radical prostatectomy or residual cancer burden \<0.25cm3.

The level of AEs defined by NCI-CTCAE v5.0. Safety assessments will be assessed and documented after initiation of study drug, regardless of relationship to study drug.

The level of complications defined by Clavien-Dindo classification.

Defined as the proportion of patients who did not experience biochemical progression or death within 3 years of initiation of darotamide treatment; biochemical progression was defined as an increase in serum PSA level to \>0.2 ng/ml with 2 consecutive increases at least 3 months apart

The proportion of subjects with positive surgical margins after radical prostatectomy

The proportion of subjects whose tumor clinical or pathological stage degradation after neoadjuvant therapy.

The proportion of subjects with a ≥98% reduction in nadir PSA from baseline PSA during neoadjuvant therapy

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Treatment With Darolutamide +/- Radiation Therapy for Patients With a Castration Resistant Cancer and Metastases Detected by Functional Imaging	NCT06276465	Prostatic Cance...	Darolutamide 30... Stereotactic bo... Androgen depriv...	18 Years -	UNICANCER
Evaluation of dAroLutamide Addition to anDrogen Deprivation Therapy and radIatioN Therapy in Newly Diagnosed Prostate Cancer With Pelvic Lymph Nodes Metastases	NCT05116475	Prostate Cancer	Darolutamide 30... Placebo of Daro...	18 Years - 120 Years	Association Pour La Recherche des Thérapeutiques Innovantes en Cancérologie
ADT +/- Darolutamide in de Novo Metastatic Prostate Cancer Patients With Vulnerable Functional Ability (PEACE6-Vulnerable)	NCT04916613	Prostate Cancer...	Darolutamide 30... Placebo Androgen depriv...	18 Years -	UNICANCER
Efficacy and Safety of Darolutamide Combined With ADT in High-risk/Very High-risk Localized Prostate Cancer	NCT05249712	Prostate Cancer	Darolutamide 30... Androgen depriv...	18 Years - 75 Years	The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
Evaluation of dAroLutamide Addition to anDrogen Deprivation Therapy and radIatioN Therapy in Newly Diagnosed Prostate Cancer With Pelvic Lymph Nodes Metastases	NCT05116475	Prostate Cancer	Darolutamide 30... Placebo of Daro...	18 Years - 120 Years	Association Pour La Recherche des Thérapeutiques Innovantes en Cancérologie

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