Treatment with darolutamide +/- radiation therapy for patients with a castration resistant cancer and metastases detected by functional imaging

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Unicancer

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

4 Oct 2024 → ongoing

Decision date (initial)

2025-03-31

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Safety, Pharmacogenomic, Efficacy

To assess whether stereotactic radiation therapy combined with darolutamide is superior in terms of radiographic progression-free survival (rPFS) to darolutamide alone for patients with CRPC having 1 to 5 oligometastases on choline/fluciclovine or PSMA PET

Secondary objectives 3

1. To assess the safety/tolerance of stereotactic radiation therapy combined with darolutamide, compared to darolutamide alone, for patients with CRPC with 1 to 5 oligometastases on choline/fluciclovine or PSMA PET, using the NCI-CTCAE 5.0.
2. To assess the efficacy of stereotactic body radiation therapy combined with darolutamide, compared to darolutamide alone, for patients with CRPC with 1 to 5 oligometastases
3. To assess the QoL of patients (with CRPC with 1 to 5 oligometastases) with stereotactic radiation therapy combined with darolutamide, compared to darolutamide alone, using the FACT-P questionnaire.

Conditions and MedDRA coding

Castrate-resistant prostate cancer with oligometastases on functional imaging (PSMA or choline/fluciclovine-positron-emission tomography).

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 16

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 with with a combination of Castrate level of testosterone: testosterone < 50ng/dl or 1.7 nmol/L. AND at least one of the following conditions: An increasing PSA level, confirmed in 3 consecutive assessments performed at least 1 week apart despite androgen deprivation therapy; • 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.
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 10^9/L, platelets count ≥100 x 10^9/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), ASAT and ALAT ≤2.5 ULN (≤5 ULN in the presence of liver metastases).
10. 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 11

1. Patient previously treated for metastatic castrate-resistant prostate cancer with chemotherapy or immunotherapy. Patients who received prior NHA are eligible provided: - they did not progress on previous NHA - they progressed on previous NHA and chemotherapy is not indicated by investigator
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) or chronic liver disease at screening
5. Patients with known allergy or severe hypersensitivity to the study treatment or any of its excipients.
6. Inability and/or difficulty 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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The superiority of stereotactic body radiation therapy combined with darolutamide to darolutamide alone for patients with CRPC having 1 to 5 oligometastases will be assessed using radiographic progression-free survival (rPFS).

Secondary endpoints 2

1. Safety/tolerance will be assessed according to the incidence of AEs (graded using the NCI CTCAE v5.0).
2. Efficacy will be assessed using the Overall survival (OS), Time to treatment failure (TTF), Prostate cancer-specific survival, Time to PSA progression, Biochemical response rate, Time to next symptomatic skeletal event (SSE), Time to pain progression and Quality of life.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Auxiliary 4

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Unicancer

Sponsor organisation

Unicancer

Address

101 Rue De Tolbiac

City

Paris

Postcode

75013

Country

France

Scientific contact point

Organisation

Unicancer

Contact name

Director of Regulatory Affairs, Quality Insurance and Pharmacovigilance

Public contact point

Organisation

Unicancer

Contact name

Director of Regulatory Affairs, Quality Insurance and Pharmacovigilance

Locations

4 EU/EEA countries · 56 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 41 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

6 submissions — initial application plus substantial / non-substantial modifications