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

NCT ID: NCT06276465

Last Updated: 2024-12-20

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE3

Total Enrollment

336 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-10-07

Study Completion Date

2032-10-07

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Prostatic Cancer, Castration-Resistant

Keywords

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Phase 3 International Multicentric Randomised Stereotactic body radiation therapy (SBRT) PET-PSMA mCRPC nmCRPC CRPC oligometastases functional imaging darolutamide

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

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

* Control arm: ADT + darolutamide.
* Experimental arm: ADT + darolutamide + SBRT.
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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ADT + darolutamide

Up to 5 years of treatment

Group Type ACTIVE_COMPARATOR

Darolutamide 300 mg

Intervention Type DRUG

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

Androgen deprivation therapy

Intervention Type DRUG

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

ADT + darolutamide + SBRT

Up to 5 years of treatment

Group Type EXPERIMENTAL

Darolutamide 300 mg

Intervention Type DRUG

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

Stereotactic body radiation therapy

Intervention Type RADIATION

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

Androgen deprivation therapy

Intervention Type DRUG

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

Interventions

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Darolutamide 300 mg

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

Intervention Type DRUG

Stereotactic body radiation therapy

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

Intervention Type RADIATION

Androgen deprivation therapy

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

Intervention Type DRUG

Other Intervention Names

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Nubeqa SBRT ADT

Eligibility Criteria

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Inclusion Criteria

1. Patient must have signed a written informed consent prior to any trial specific procedures. When the patient is physically unable to give their written consent, a trusted person of their choice, independent from the investigator or the sponsor, can confirm in writing the patient's consent.
2. Patients aged ≥18 years.
3. Patient with histologically confirmed of adenocarcinoma prostate cancer without small cell or pure endocrine features.
4. Patient with a history of local treatment with curative intent for localised prostate cancer, including surgery or radiotherapy.
5. Patients with castration resistant prostate cancer, defined as either:

* An increasing PSA level, confirmed in 3 consecutive assessments performed at least 1 week apart. This despite androgen deprivation therapy and castrate levels of testosterone.
* Tumour progression of soft tissue according to the response criteria in solid tumours (RECIST) version (v)1.1.
* Tumour progression on bone scan, according to PCWG3 criteria.

N.B. The two latter conditions only apply to the M1CRPC population.
6. Detection of 1 to 5 metastatic sites (pelvic lymph nodes included) on new generation PET using either choline, fluciclovine, or PSMA as tracer.
7. All metastatic sites must be amenable to stereotactic radiation therapy.
8. Patient with normal haematological function: absolute neutrophil count (ANC) \>1.0 x 10⁹/L, platelets count ≥100 x 10⁹/L, and haemoglobin ≥9.0 g/dL.
9. Patient with normal liver function with total bilirubin ≤1.5 upper limit of normal (ULN) (unless documented Gilbert's syndrome), aspartate aminotransferase (ASAT) and alanine aminotransferase (ALAT) ≤2.5 ULN (≤5 ULN in the presence of liver metastases).
10. Adequate liver function with bilirubin \<3 mg/dL and albumin \>2.5 g/dL.
11. Systolic blood pressure \<160 mmHg and diastolic blood pressure \<100 mmHg, as documented at baseline. Patients with hypertension are eligible if their hypertension is controlled and they meet all other eligibility criteria.
12. Adequate kidney function with a creatinine clearance \>30 mL/min (Cockcroft-Gault).
13. Patient with Eastern Cooperative Oncology group (ECOG) performance status (PS) ≤1.
14. Patient is willing to use contraceptive during and for at least 1 week after discontinuing darolutamide.
15. Patient affiliated to the social security system (or equivalent according to local regulations for participation in clinical trials).
16. Patient is willing and able to comply with the protocol for the duration of the trial including undergoing treatment and scheduled visits, and examinations including follow-up.

Exclusion Criteria

1. Patient previously treated for metastatic prostate cancer with a novel hormonal agent (NHA), a CYP17 inhibitor, ketoconazole, chemotherapy, or immunotherapy.
2. A history of cancer, other than the prostate cancer under study, within the 3 years prior to study inclusion, excluding cured localised cancer such as non-melanomatous skin cancer and non-muscle invasive bladder cancer.
3. Presence of an uncontrolled disease or affection that according to the investigator will hinder compliance with the trial procedures or requires hospitalisation.
4. Known to have active viral hepatitis, active human immunodeficiency virus (HIV) A at screening.
5. Patients with known allergy or severe hypersensitivity to the study treatment or any of its excipients.
6. Inability to swallow oral medications.
7. Gastrointestinal disorder or procedure that can be expected to interfere significantly with the absorption of study treatment.
8. Any of the following within 6 months before randomisation: stroke, myocardial infarction, severe/unstable angina pectoris, coronary/peripheral artery bypass graft; congestive heart failure New York Heart Association (NYHA) Class III or IV.
9. Patients participating in another therapeutic trial within the 30 days prior to randomisation.
10. Patients unable to comply with trial obligations for geographic, social, or physical reasons, or who are unable to understand the purpose and procedures of the trial.
11. Person deprived of their liberty or under protective custody or guardianship.
Minimum Eligible Age

18 Years

Eligible Sex

MALE

Accepts Healthy Volunteers

No

Sponsors

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Bayer

INDUSTRY

Sponsor Role collaborator

UNICANCER

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Ronan FLIPPOT, MD

Role: PRINCIPAL_INVESTIGATOR

Gustave Roussy (Villejuif, France)

David PASQUIER, MD

Role: PRINCIPAL_INVESTIGATOR

Centre Oscar Lambret, Lille University (Lille, France)

Locations

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Groupe Hospitalier Bretagne Sud

Lorient, , France

Site Status RECRUITING

Centre Azuréen de Cancérologie

Mougins, , France

Site Status RECRUITING

CHU de Saint-Etienne

Saint-Etienne, , France

Site Status RECRUITING

Gustave Roussy Cancer Campus

Villejuif, , France

Site Status RECRUITING

Countries

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France

Central Contacts

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Catherine LEGER

Role: CONTACT

Phone: 0033 7 79 83 23 98

Email: [email protected]

Meryem BRIHOUM

Role: CONTACT

Phone: 0033 1 80 50 12 95

Email: [email protected]

Facility Contacts

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Guillaume BERA, MD

Role: primary

Philippe RONCHIN, MD

Role: primary

Thomas REYNAUD, MD

Role: primary

Ronan FLIPPOT, MD

Role: primary

Other Identifiers

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2023-507482-26-00

Identifier Type: OTHER

Identifier Source: secondary_id

UC-GTG-2306

Identifier Type: -

Identifier Source: org_study_id