A clinical study evaluating the benefits of apalutamide, a novel drug targeting prostate cancer growth, in combination with radiotherapy and hormonetherapy in prostate cancer patients in whom PSA increases following surgery

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

2 Dec 2019 → ongoing

Decision date (initial)

2024-07-31

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Janssen pharmaceutica

External identifiers

EU CT number

2024-514829-36-00

EudraCT number

2017-000155-21

ClinicalTrials.gov

NCT04181203

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety, Therapy

To evaluate the clinical benefit of adding the androgen receptor competitive inhibitor apalutamide in combination with a Luteinizing Hormone Releasing Hormone (LHRH) agonist
concomitantly to salvage radiotherapy (SRT) after biochemical progression following radical prostatectomy in patients with high-risk prostate adenocarcinoma. The clinical benefit will be evaluated using the progression-free survival (PFS) rate at 5 years.

Secondary objectives 6

1. To evaluate the prostate-cancer specific survival rate
2. To evaluate the overall survival rate at 10 years
3. To evaluate the biochemical relapse rate
4. To evaluate the time to castration resistant prostate cancer
5. To evaluate safety
6. To assess patients’ quality of life

Conditions and MedDRA coding

High-risk biochemically-relapsed prostate adenocarcinoma following radical prostatectomy.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 14

1. Patients must have signed a written informed consent form prior to any trial specific procedures
2. Age ≥ 18 years old and ≤ 80 years old
3. Histologically confirmed diagnosis of prostate adenocarcinoma treated primarily with radical prostatectomy
4. Tumor stage pT2, pT3 or pT4* (*only in case of bladder neck involvement)
5. Patients should have no clinical and radiological signs (18FCH-PET CT-scan or 68Ga-PSMA-PET CT-scan) of metastatic disease. Patients with a local relapse or pelvic nodal relapse (N1) detected on PET CT-scan can be randomized
6. ECOG performance status ≤ 1
7. PSA ≥ 0.2 ng/mL at the time of randomization with an elevation of PSA over three consecutive PSA increases over a 1-month interval minimum
8. At least 3 months between radical prostatectomy and randomization
9. High-risk features as defined by at least one of these characteristics: PSA at relapse > 0.5 ng/mL or Gleason score > 7 or tumor stage pT3b or resection margins R0 or PSA doubling time ≤ 6 months or pelvic lymph node relapse (N1, ≤ 5 lymph nodes)
10. Adequate renal function: serum creatinine < 1.5 x upper limit of normal (ULN) or a calculated corrected creatinine clearance ≥ 60 mL/min according to the Cockcroft-Gault formula, creatinemia < 2 ULN
11. Adequate hepatic function: total bilirubin ≤ 1.5 x ULN (unless documented Gilbert’s syndrome), AST and ALT ≤ 2.5 x ULN
12. Patients with QTc prolongation < 500 ms*, inclusion should considered after close benefit/risk assessment and cardiologist advice *In patients with a history or risk factors for QT prolongation, and in patients receiving concomitant medicines that may prolong the QT interval, a cardiologist should assess the benefit / risk balance taking into account the potential risk of torsade de pointes before initiating treatment with apalutamide
13. Patients must be willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations
14. Patients must be affiliated to the Social Security System

Exclusion criteria 20

1. Previous treatment with hormone therapy for prostate cancer
2. Uncontrolled hypertension (defined as systolic blood pressure (BP) ≥ 160 mmHg or diastolic BP ≥ 100 mmHg). Patients with a history of hypertension are allowed provided blood pressure is controlled by anti-hypertensive treatment
3. History of seizure or condition that may pre-dispose to seizure (including, but not limited to prior stroke, transient ischemic attack or loss of consciousness ≤ 1 year prior to randomization; brain arteriovenous malformation or intracranial masses such as schwannomas and meningiomas that are causing edema or mass effect)
4. Medications known to lower the seizure threshold must be discontinued or substituted at least 4 weeks prior to study entry
5. Clinically significant history of liver disease consistent with Child-Pugh class B or C
6. Histology other than adenocarcinoma
7. Surgical or chemical castration
8. Other malignancy except adequately treated basal cell carcinoma of the skin or other malignancy from which the patient has been cured for at least 5 years
9. Previous pelvic radiotherapy
10. More than 5 (>5) pelvic lymph node relapses
11. Paraaortic, thoracic or supaclavicular nodal relapse (M1a)
12. History of Inflammatory bowel disease or any malabsorption syndrome or conditions that would interfere with enteral absorption
13. Severe or unstable angina, myocardial infarction, symptomatic congestive heart failure, arterial or venous thromboembolic events (e.g pulmonary embolism, cerebrovascular accident including transient ischemic attacks) or clinically significant ventricular arrhythmias within 6 months prior to randomization
14. Certain risk factors for abnormal heart rhythmas/QT prolongation: torsade de pointes ventricular arrhythmias (e.g, heart failure, hypokalemia, or a family history of a long QT syndrome), a QT or corrected QT (QTc) interval > 500 ms at baseline
15. Medications known to prolong QTc
16. Known hypersensitivity to apalutamide or to any of its components
17. Galactosemia, Glucose-galactose malabsorption or lactase deficiency
18. Inability or willingness to swallow oral medication
19. Individual deprived of liberty or placed under the authority of a tutor
20. Patients already included in another therapeutic trial with an experimental drug or having been given an experimental drug within the 30 days before inclusion

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary endpoint is the 5-year-progression free survival (PFS) accordingly to PERCIST 1.0 and RECIST 1.1 criteria. PFS idefined as time from date of randomization to date of first evidence of loco-regional recurrences, or distant metastases, or death from any cause whichever occurs first, or date of last known follow-up alive without any such events. Evidence of loco-regional recurrences is evaluated on PET CT; Evidence of distant metastases is evaluated on PET CT

Secondary endpoints 6

1. Cancer-specific overall survival is defined as the time from the date of randomization to the date of death related to prostate cancer or the date of last known follow-up alive.
2. Overall survival (OS) will be assessed at 10 years. OS is defined as the time from the date of randomization to the date of death from any cause or the date of last known follow-up alive.
3. Biochemical relapse-free survival will be retrospectively defined by the interval between the date of randomization and the date of the first PSA elevation following the 6-months treatment in both arms (PSA ≥ 0.5 ng/mL confirmed by two consecutive PSA increases over a 2-months interval).If no biochemical relapse is observed, the PSA concentration will be measured every 6 months for 5 years and every year thereafter.
4. Time to castration resistance is defined as the time from date of randomization to date of appearance of castration resistance defined in the EAU guidelines (Cornford Eur Urol 2017). Castration-resistant prostate cancer (CRPC) is defined as castrate serum testosterone <50 ng/dl or 1.7 nmol/l plus one of the following types of progression: - Biochemical progression - Radiologic progression:
5. Safety: Frequency, nature and severity of adverses events will be assessed according to the NCI CTCAE version 5.0 (see Appendix 4) Acute toxicity related to radiotherapy is defined as occurring during radiotherapy and up to 3 months after completion of radiotherapy. Late toxicity related to radiotherapy is defined as occurring later than 3 months after end of radiotherapy. The tolerance will be evaluated up until 10 years.
6. Patient-reported outcomes: Quality of life will be assessed at baseline, at end of SRT, at end of treatment visit and at every follow up visit until disease progression by using:  EORTC QLQ-C30 questionnaire  EORTC QLQ-PR25 questionnaire  IIEF-5 questionnaire  IADL scale for patients ≥ 75 years old

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Unicancer

Sponsor organisation

Unicancer

Address

101 Rue De Tolbiac

City

Paris Cedex 13

Postcode

75654

Country

France

Scientific contact point

Organisation

Unicancer

Contact name

Nourredine AIT RAHMOUNE

Public contact point

Organisation

Unicancer

Contact name

Nourredine AIT RAHMOUNE

Locations

1 EU/EEA country · 28 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 10 files

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

Application history

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