RAndomized, open label, multicenter study of Docetaxel versus an Androgen Receptor-targeted agent (abiraterone orenzalutamide) as first-line of therapy in mCRPC patients with adverse prognostic factors (RADAR-1 CRPC)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

1 Oct 2020 → ongoing

Decision date (initial)

2024-11-26

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-518623-30-00

EudraCT number

2019-003761-17

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

To investigate if docetaxel is superior to Androgen Receptor-targeted agent (abiraterone+prednisone or enzalutamide) for treatment of patients with mCRPC BRCA negative or unknown and negative
prognostic factors in terms of PFS.

Secondary objectives 1

1. To investigate if docetaxel is superior to Androgen Receptor-targeted agent (abiraterone + prednisone or enzalutamide) for treatment of patients with mCRPC BRCA negative or unknown and negative prognostic factors in terms of biochemical response, radiographic progression, overall survival and quality of life

Conditions and MedDRA coding

metastatic castration resistant prostate cancer without mutations of BRCA1/2 genes or unknown

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 13

1. Willing and able to provide written informed consent
2. Male aged 18 years and above
3. Histologically or cytological confirmed adenocarcinoma of the prostate
4. Metastatic disease documented by positive bone scan or metastatic lesions other than liver or visceral metastasis on CT, MRI. If lymph node metastasis is the only evidence of metastasis, it must be ≥ 2 cm in diameter. Alternatively, metastatic disease can be diagnosed by PET-Choline or PSMA.
5. Prostate cancer progression documented by PSA according to PCWG2 or radiographic progression according to modified RECIST criteria
6. At least one negative prognostic features between: I. Mildly symptomatic prostate cancer defined as per BPI Question #3 (worst pain in last 24 hours) value 2 or 3 or II. Asymptomatic prostate cancer defined as per BPI Question #3 (worst pain in last 24 hours) value 0 or 1 and at least one between - PSA≥80 ng/dl ; - Gleason Score ≥ 8; - PSA doubling time ≤ 3 months; - Time from start ADT to CRPC less < 1 year
7. No evidence of mutation in BRCA1 or genes or tumor tissue not evaluated for quality reasons (status unknown)
8. Surgically or medically castrated, with testosterone levels of < 50 ng/dL (< 2.0 nM)
9. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 2
10. Adequate bone marrow and chemistry values defined as: a. Hemoglobin ≥ 10.0 g/dL independent of transfusion b. Neutrophil count ≥1500 x 109/L c. Platelet count ≥100,000/μL d. Serum albumin ≥ 3.5 g/dL e. Serum creatinine < 1.5 x ULN or a calculated creatinine clearance ≥ 60 mL/min f. Serum potassium ≥ 3.5 mmol/L g. Liver function: - Serum bilirubin < 1.5 x ULN (except for patients with documented Gilbert’s disease); - AST or ALT < 2.5 x ULN
11. Able to swallow the study drug whole as a tablet
12. Life expectancy of at least 6 months
13. Patients who have partners of childbearing potential must be willing to use a method of birth control with adequate barrier protection as determined to be acceptable by the principal investigator and sponsor during the study and for 13 weeks after last study drug administration

Exclusion criteria 16

1. Active infection or other medical condition that would make prednisone/prednisolone (corticosteroid) use contraindicated
2. Pathological finding consistent with small cell carcinoma of the prostate greater than 10%
3. Known brain metastasis
4. Use of major opiate analgesics for cancer-related pain (codeine and tramadol are allowed)
5. Previous cytotoxic chemotherapy, or biologic therapies for the treatment of castrationsensitive or castration-resistant prostate cancer (prior use of bicalutamide is permitted). Previous use of new generation androgen receptor inhibitors for castration-sensitive disease is permitted if at least one year has passed since their discontinuation or if treatment has lasted longer than 36 months without evidence of biochemical and radiological progression
6. Radiation therapy for treatment of the primary tumour within 6 weeks of Cycle 1, Day 1
7. Radiation or radionuclide therapy for treatment of metastatic CRPC and CSPC
8. Bicalutamide, nilutamide within 6 weeks of Cycle 1 Day 1
9. Uncontrolled hypertension (systolic BP ≥ 160 mmHg or diastolic BP ≥ 95 mmHg). Patients with a history of hypertension are allowed provided blood pressure is controlled by antihypertensive treatment
10. A marked baseline prolongation of QT/QTc interval (e.g., repeated demonstration of a QTc interval >450 ms) or history of additional risk factors for “torsaides de pointes” (e.g., heart failure, hypokalemia, family history of Long QT Syndrome) or the use of concomitant medications that prolong the QT/QTc interval (at least those of class IA and III).
11. Active or symptomatic viral hepatitis or chronic liver disease
12. Clinically significant heart disease as evidenced by myocardial infarction, or arterial thrombotic events in the past 6 months, severe or unstable angina, or New York Heart Association (NYHA) Class II-IV heart disease or cardiac ejection fraction measurement of < 50% at baseline
13. Uncontrolled Atrial Fibrillation, or other uncontrolled cardiac arrhythmia requiring therapy
14. Other malignancy with a previous diagnosis within 5 years (with the exclusions of NMIBC)
15. Concomitant medications as reported in section 7
16. Known hypersensitivity to docetaxel, abiraterone or enzalutamide active principles and any excipients

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. To compare the radiographic Progression-Free Survival (rPFS) rate at 9 months of chemotherapy (Arm A, docetaxel plus prednisone) versus androgen receptor targeted therapy (Arm B, enzalutamide or abiraterone acetate plus prednisone) in mCRPC BRCA negative or unknown patients with adverse prognostic factors

Secondary endpoints 3

1. To compare efficacy of docetaxel plus prednisone to enzalutamide or abiraterone acetate plus prednisone for: - PSA response rate; - Median rPFS; - Overall survival
2. To compare the safety of each treatment amog docetaxel abiraterone end enzalutamide
3. To compare Health-Related Quality Of Life (HRQOL) according to FACT-P questionnaire and Health status/utility (EQ-5D-5L) test

Investigational products

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

Test 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Sponsor organisation

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Address

Largo Francesco Vito 1

City

Rome

Postcode

00168

Country

Italy

Scientific contact point

Organisation

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Contact name

Roberto Iacovelli

Public contact point

Organisation

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Contact name

Roberto Iacovelli

Locations

1 EU/EEA country · 21 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 9 files

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

Application history

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