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

NCT06276465 | Recruiting Phase 3 DMC

• 2 other identifiers: UC-GTG-23062023-507482-26-00
• Study Type: interventional
• Target: 336
• Locations: 1 country
• Sites: 4

Brief Summary

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.

Conditions

Prostatic Cancer, Castration-Resistant

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Radiographic Progression-free survival (rPFS)

  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.

  From randomization to disease progression or death, up to 5 years.

Secondary Outcomes (10)

• Time to treatment failure (TTF)

  From randomization to discontinuation of darolutamide, up to 5 years

• Overall survival (OS)

  From randomization to death from any cause, up to 5 years.

• Prostate cancer-specific survival

  From randomization to death due to prostate cancer, up to 5 years.

• Time to PSA progression

  From randomization to PSA progression, up to 5 years.

• Biochemical response rate

  Throughout study completion, up to 5 years.

Study Arms (2)

ADT + darolutamide

ACTIVE COMPARATOR

Up to 5 years of treatment

Drug: Darolutamide 300 mg; Drug: Androgen deprivation therapy

ADT + darolutamide + SBRT

EXPERIMENTAL

Up to 5 years of treatment

Drug: Darolutamide 300 mg; Radiation: Stereotactic body radiation therapy; Drug: Androgen deprivation therapy

Interventions

Darolutamide 300 mg DRUG

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

Also known as: Nubeqa

ADT + darolutamide; ADT + darolutamide + SBRT

Stereotactic body radiation therapy RADIATION

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

Also known as: SBRT

ADT + darolutamide + SBRT

Androgen deprivation therapy DRUG

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

Also known as: ADT

ADT + darolutamide; ADT + darolutamide + SBRT

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Patients aged ≥18 years.
• Patient with histologically confirmed of adenocarcinoma prostate cancer without small cell or pure endocrine features.
• Patient with a history of local treatment with curative intent for localised prostate cancer, including surgery or radiotherapy.
• 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.
• Detection of 1 to 5 metastatic sites (pelvic lymph nodes included) on new generation PET using either choline, fluciclovine, or PSMA as tracer.
• All metastatic sites must be amenable to stereotactic radiation therapy.
• 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.
• 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).
• Adequate liver function with bilirubin \<3 mg/dL and albumin \>2.5 g/dL.
• 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.

You may not qualify if:

• Patient previously treated for metastatic prostate cancer with a novel hormonal agent (NHA), a CYP17 inhibitor, ketoconazole, chemotherapy, or immunotherapy.
• Presence of an uncontrolled disease or affection that according to the investigator will hinder compliance with the trial procedures or requires hospitalisation.
• Known to have active viral hepatitis, active human immunodeficiency virus (HIV) A at screening.
• Patients with known allergy or severe hypersensitivity to the study treatment or any of its excipients.
• Inability to swallow oral medications.
• Gastrointestinal disorder or procedure that can be expected to interfere significantly with the absorption of study treatment.
• 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.
• Patients participating in another therapeutic trial within the 30 days prior to randomisation.
• 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.
• Person deprived of their liberty or under protective custody or guardianship.

Sponsors & Collaborators

• UNICANCER: lead
• Bayer: collaborator

Study Sites (4)

Groupe Hospitalier Bretagne Sud

Lorient, 56322, France

RECRUITING

Centre Azuréen de Cancérologie

Mougins, 06250, France

RECRUITING

CHU de Saint-Etienne

Saint-Etienne, 42055, France

RECRUITING

Gustave Roussy Cancer Campus

Villejuif, 94805, France

RECRUITING

MeSH Terms

Conditions

Prostatic Neoplasms, Castration-Resistant

Interventions

darolutamide; Radiosurgery; Androgen Antagonists

Condition Hierarchy (Ancestors)

Prostatic Neoplasms; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Radiotherapy; Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques; Hormone Antagonists; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses

Study Officials

• Ronan FLIPPOT, MD

  Gustave Roussy (Villejuif, France)

  PRINCIPAL INVESTIGATOR

• David PASQUIER, MD

  Centre Oscar Lambret, Lille University (Lille, France)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Catherine LEGER

CONTACT

0033 7 79 83 23 98; c-leger@unicancer.fr

Meryem BRIHOUM

CONTACT

0033 1 80 50 12 95; m-brihoum@unicancer.fr

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Eligible patients will be randomly allocated in a 1:1 ratio to either the: * Control arm: ADT + darolutamide. * Experimental arm: ADT + darolutamide + SBRT.

Study Record Dates

• First Submitted: February 16, 2024
• First Posted: February 26, 2024
• Study Start: October 7, 2024
• Primary Completion (Estimated): October 15, 2029
• Study Completion (Estimated): October 7, 2032
• Last Updated: December 20, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

FR (4)