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

NCT ID: NCT04181203

Last Updated: 2025-07-30

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 490 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-01-09
• Study Completion Date: 2033-12-28

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.

Detailed Description

The purpose of the CARLHA-2 study is to determine if the combination of apalutamide with 6 months of LHRH agonists and radiotherapy results in an improvement of progression-free survival (PFS) in comparison to the combination of 6 months of LHRH agonists with radiotherapy in high-risk postprostatectomy biochemically relapsed prostate cancer patients.

Radical prostatectomy must have been done at least 6 months before inclusion and is not part of this study.

Patients after radical prostatectomy and biochemical relapse will be randomized in a 1:1 ratio to receive either 6 months of LHRH agonists + SRT or 6 months of LHRH agonists + SRT + 6 months of apalutamide.

The stratification variables include Gleason score, prostate-specific antigen (PSA), negative resection margins, extension to seminal vesicle(s), and PSA doubling time.

Conditions

Prostate Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

SRT + 6 months of LHRHa

• 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.

Group Type: ACTIVE_COMPARATOR

Salvage radiotherapy (SRT)

Intervention Type: 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.

Luteinising Hormone Releasing Hormone agonist (LHRHa)

Intervention Type: 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.

SRT + 6 months of LHRHa + 6 months of Apalutamide

• 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.

Group Type: EXPERIMENTAL

Apalutamide

Intervention Type: DRUG

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

months.

Salvage radiotherapy (SRT)

Intervention Type: 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.

Luteinising Hormone Releasing Hormone agonist (LHRHa)

Intervention Type: 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.

Interventions

Apalutamide

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

months.

Intervention Type: DRUG

Salvage radiotherapy (SRT)

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.

Intervention Type: RADIATION

Luteinising Hormone Releasing Hormone agonist (LHRHa)

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.

Intervention Type: DRUG

Other Intervention Names

ARN-509; leuprolide, goserelin, triptorelin acetate

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

7. 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

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), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 x ULN

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

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

1. Previous treatment with hormone therapy for prostate cancer

2. Histology other than adenocarcinoma

3. Surgical or chemical castration

4. 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

5. Previous pelvic radiotherapy

6. More than 5 (>5) pelvic lymph node relapses

7. Paraaortic, thoracic or supaclavicular nodal relapse (M1a)

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

9. 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

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

11. 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)

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

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 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

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

Janssen Pharmaceutica

INDUSTRY

Sponsor Role: collaborator

UNICANCER

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Stéphane SUPIOT

Role: PRINCIPAL_INVESTIGATOR

Institut de Cancérologie de l'Ouest - Saint Herblain

Locations

Clinique Claude Bernard

Albi, , France

Institut de Cancérologie de l'Ouest

Angers, , France

Institut Bergonié

Bordeau, , France

Centre Georges François LECLERC

Dijon, , France

Centre Hospitalier Emile ROUX

Le Puy-en-Velay, , France

Centre Oscar Lambret

Lille, , France

Institut de Cancérologie de Montpellier

Montpellier, , France

Centre Antoine Lacassagne

Nice, , France

Institut Jean Godinot

Reims, , France

Centre Henri Becquerel

Rouen, , France

Institut de Cancérologie de l'Ouest

Saint-Herblain, , France

Institut de Cancérologie de la Loire Lucien Neuwirth

Saint-Priest-en-Jarez, , France

Institut de Cancérologie Paris Nord

Sarcelles, , France

Centre Paul STRAUSS

Strasbourg, , France

Clinique Pasteur - ONCORAD

Toulouse, , France

Countries

France

Other Identifiers

2017-000155-21

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

GETUG-AFU33 UC-0160/1702

Identifier Type: -

Identifier Source: org_study_id