Combined Apalutamide, Radiotherapy, and LHRH Agonist in Prostate Cancer Patients After Prostatectomy

• Status: Recruiting
• Trial end date: 2033-12-28
• Target enrollment: 0
• Participant gender: Male

Summary

This is a multicenter, randomized, open label, phase III study comparing the efficacy and safety of apatulamide combined with concomitant prostate-bed salvage radiotherapy (SRT) and androgen deprivation therapy (ADT) versus concomitant prostate-bed SRT and ADT in high-risk postprostatectomy biochemically relapsed prostate cancer patients.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: UNICANCER
• Collaborator: Janssen Pharmaceutica
• Treatments: Goserelin; Hormones; Leuprolide; Triptorelin Pamoate

Criteria

Inclusion Criteria:

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. Pathologically proven to be lymph node negative by pelvic lymphadenectomy (N0) or lymph node status pathologically unknown (undissected pelvic lymph nodes [Nx])

5. Tumor stage pT2, pT3 or pT4* (*only in case of bladder neck involvement)

6. 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 detected on PET CT-scan can be randomized

7. Eastern Cooperative Oncology Group (ECOG) performance status ≤1

8. PSA ≤0.5 ng/mL after radical prostatectomy (dosage performed within 3 months after surgery)

9. PSA ≥0.2 ng/mL and ≤2 ng/mL at the time of randomization with an elevation of PSA over three consecutive assays

10. At least 3 months between radical prostatectomy and inclusion

11. 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

12. 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

13. Adequate hepatic function: total bilirubin ≤1.5 x ULN (unless documented Gilbert's syndrome), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 x ULN

14. Patients with QTc prolongation <500 ms, inclusion should considered after close benefit/risk assessment and cardiologist advice

15. Patients with female partners of reproductive potential should agree to use effective contraceptive method during treatment period and for 3 months after the last dose of apalutamide or for 6 months after the last fraction of radiotherapy

16. 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

17. Patients must be affiliated to the Social Security System

Exclusion Criteria:

1. Histologically proven lymph nodes involvement at initial lymphadenectomy: pN1, pN2, pN3

2. Previous treatment with hormone therapy for prostate cancer

3. Histology other than adenocarcinoma

4. Surgical or chemical castration

5. 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

6. Previous pelvic radiotherapy

7. History of Inflammatory bowel disease or any malabsorption syndrome or conditions that would interfere with enteral absorption

8. Uncontrolled hypertension (defined as systolic blood pressure (BP) ≥140 mmHg or diastolic BP ≥90 mmHg). Patients with a history of hypertension are allowed provided blood pressure is controlled by anti-hypertensive treatment

9. Clinically significant history of liver disease consistent with Child-Pugh class B or C

10. 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)

11. Medications known to lower the seizure threshold must be discontinued or substituted at least 4 weeks prior to study entry

12. 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

13. Certain risk factors for abnormal heart rhythms/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

14. Medications known to prolong QTc

15. Known hypersensitivity to apalutamide or to any of its components

16. Galactosemia, Glucose-galactose malabsorption or lactase deficiency

17. Inability or willingness to swallow oral medication

18. Individual deprived of liberty or placed under the authority of a tutor

19. Patients already included in another therapeutic trial with an experimental drug or having been given an experimental drug within the 30 days before inclusion