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

NCT04181203 | Active Not Recruiting Phase 3 DMC

• 2 other identifiers: GETUG-AFU33 UC-0160/17022017-000155-21
• Study Type: interventional
• Target: 490
• Locations: 1 country
• Sites: 15

Brief 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.

Conditions

Prostate Cancer

Keywords

Apalutamide; Salvage radiotherapy; Radical prostatectomy; PSA

Outcome Measures

Primary Outcomes (1)

• Progression-free survival (PFS)

  PFS is defined as the time from the date of randomization to the date of first evidence of loco-regional recurrences, or distant metastases, or death from any cause whichever occurs first, or the date of last known follow-up alive without any such events.

  5 years

Secondary Outcomes (9)

• Cancer-specific overall survival

  10 years

• Overall survival (OS)

  10 years

• Biochemical relapse-free survival

  10 years

• Time to castration resistance

  10 years

• Adverse events graded according to the NCI Common Terminology Criteria for Adverse Events version 5.0

  Throughout study completion, up to 10 years

Study Arms (2)

SRT + 6 months of LHRHa

ACTIVE COMPARATOR

* Treatment with LHRHa will start 4 weeks before the first RT fraction (i.e Day 1 of Week 1 of treatment period.) The total duration of the LHRHa treatment is 6 months. * SRT will start 4 weeks after the first administration of LHRHa (i.e Day 1 of Week 5 of treatment period.). The total duration of SRT is 6.5 weeks.

Radiation: Salvage radiotherapy (SRT); Drug: Luteinising Hormone Releasing Hormone agonist (LHRHa)

SRT + 6 months of LHRHa + 6 months of Apalutamide

EXPERIMENTAL

* Treatment with LHRHa will start 4 weeks before the first RT fraction (i.e Day 1 of Week 1 of treatment period.) The total duration of the LHRHa treatment is 6 months. * Treatment with apalutamide (240 mg PO daily) should start the same day as the first LHRHa administration, for 6 months. * SRT will start 4 weeks after the first administration of LHRHa (i.e Day 1 of Week 5 of treatment period.). The total duration of SRT is 6.5 weeks.

Drug: Apalutamide; Radiation: Salvage radiotherapy (SRT); Drug: Luteinising Hormone Releasing Hormone agonist (LHRHa)

Interventions

Apalutamide DRUG

240 mg PO daily should start the same day as the first LHRHa administration for 6 months. months.

Also known as: ARN-509

SRT + 6 months of LHRHa + 6 months of Apalutamide

Salvage radiotherapy (SRT) RADIATION

The SRT treatment will be administered to a total dose of 66 Gy (in 33 fractions of 2 Gy) directed at the prostate bed with an additional 56.1 Gy (in 33 fractions of 1.7 Gy) directed at the pelvis region. The pelvis will be irradiated in all patients. An additional simultaneously integrated boost of 69.3 Gy (in 33 fractions of 2.1 Gy) can be delivered to a local relapse based on Positron Emission Tomography - Computed Tomography (PET/CT) and Magnetic Resonance Imaging (MRI) images.

SRT + 6 months of LHRHa; SRT + 6 months of LHRHa + 6 months of Apalutamide

Luteinising Hormone Releasing Hormone agonist (LHRHa) DRUG

Doses of LHRHa may vary due to availability of different brand names and pharmaceutical forms. It will be left to the discretion of the investigator.

Also known as: leuprolide, goserelin, triptorelin acetate

SRT + 6 months of LHRHa; SRT + 6 months of LHRHa + 6 months of Apalutamide

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have signed a written informed consent form prior to any trial specific procedures
• Age ≥18 years old and ≤80 years old
• Histologically confirmed diagnosis of prostate adenocarcinoma treated primarily with radical prostatectomy
• Tumor stage pT2, pT3 or pT4\* (\*only in case of bladder neck involvement)
• 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
• Eastern Cooperative Oncology Group (ECOG) performance status ≤1
• PSA ≥0.2 ng/mL at the time of randomization with an elevation of PSA over three consecutive assays. PSA increases over a 1-month interval minimum
• At least 3 months between radical prostatectomy and randomization.
• 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)
• 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
• 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
• 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
• Patients must be affiliated to the Social Security System

You may not qualify if:

• Previous treatment with hormone therapy for prostate cancer
• Histology other than adenocarcinoma
• Surgical or chemical castration
• 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
• Previous pelvic radiotherapy
• More than 5 (\>5) pelvic lymph node relapses
• Paraaortic, thoracic or supaclavicular nodal relapse (M1a)
• History of Inflammatory bowel disease or any malabsorption syndrome or conditions that would interfere with enteral absorption
• 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
• Clinically significant history of liver disease consistent with Child-Pugh class B or C
• 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)
• Medications known to lower the seizure threshold must be discontinued or substituted at least 4 weeks prior to study entry
• 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
• 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
• Medications known to prolong QTc

Sponsors & Collaborators

• UNICANCER: lead
• Janssen Pharmaceutica: collaborator

Study Sites (15)

Clinique Claude Bernard

Albi, France

Location

Institut de Cancérologie de l'Ouest

Angers, France

Location

Institut Bergonié

Bordeau, France

Location

Centre Georges François LECLERC

Dijon, France

Location

Centre Hospitalier Emile ROUX

Le Puy-en-Velay, France

Location

Centre Oscar Lambret

Lille, France

Location

Institut de Cancérologie de Montpellier

Montpellier, France

Location

Centre Antoine Lacassagne

Nice, France

Location

Institut Jean Godinot

Reims, France

Location

Centre Henri Becquerel

Rouen, France

Location

Institut de Cancérologie de l'Ouest

Saint-Herblain, France

Location

Institut de Cancérologie de la Loire Lucien Neuwirth

Saint-Priest-en-Jarez, France

Location

Institut de Cancérologie Paris Nord

Sarcelles, France

Location

Centre Paul STRAUSS

Strasbourg, France

Location

Clinique Pasteur - ONCORAD

Toulouse, France

Location

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

apalutamide; Leuprolide; Goserelin; Triptorelin Pamoate

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Gonadotropin-Releasing Hormone; Pituitary Hormone-Releasing Hormones; Hypothalamic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins

Study Officials

• Stéphane SUPIOT

  Institut de Cancérologie de l'Ouest - Saint Herblain

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: November 26, 2019
• First Posted: November 29, 2019
• Study Start: January 9, 2020
• Primary Completion (Estimated): September 28, 2028
• Study Completion (Estimated): December 28, 2033
• Last Updated: July 30, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

FR (15)