Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Combined Apalutamide, Radiotherapy, and LHRH Agonist in Prostate Cancer Patients After Prostatectomy (CARLHA-2)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04181203
Recruitment Status : Suspended (Temporary suspension since March 20 due to COVID-19 pandemic)
First Posted : November 29, 2019
Last Update Posted : April 24, 2020
Sponsor:
Collaborator:
Janssen Pharmaceutica
Information provided by (Responsible Party):
UNICANCER

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.

Condition or disease Intervention/treatment Phase
Prostate Cancer Drug: Apalutamide Radiation: Salvage radiotherapy (SRT) Drug: Luteinising Hormone Releasing Hormone agonist (LHRHa) Phase 3

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 490 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open Label, Randomized, Phase III Study, Evaluating the Efficacy of a Combination of Apalutamide With Radiotherapy and LHRH Agonist in High-risk Postprostatectomy Biochemically Relapsed Prostate Cancer Patients
Actual Study Start Date : January 9, 2020
Estimated Primary Completion Date : September 28, 2028
Estimated Study Completion Date : December 28, 2033

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Prostate Cancer

Arm Intervention/treatment
Active Comparator: 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.
Radiation: 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.


Drug: 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.
Other Name: leuprolide, goserelin, triptorelin acetate

Experimental: 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.
Drug: Apalutamide

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

months.

Other Name: ARN-509

Radiation: 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.


Drug: 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.
Other Name: leuprolide, goserelin, triptorelin acetate




Primary Outcome Measures :
  1. Progression-free survival (PFS) [ Time Frame: 5 years ]
    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.


Secondary Outcome Measures :
  1. Cancer-specific overall survival [ Time Frame: 10 years ]
    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) [ Time Frame: 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 [ Time Frame: 10 years ]
    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-month interval).

  4. Time to castration resistance [ Time Frame: 10 years ]
    The time to castration resistance is defined as the time from the date of randomization to the date of appearance of castration resistance defined in the European Association of Urology (EAU) guidelines.

  5. Adverse events graded according to the NCI Common Terminology Criteria for Adverse Events version 5.0 [ Time Frame: Throughout study completion, up to 10 years ]
    The NCI Common Terminology Criteria for Adverse Events is a descriptive terminology which can be utilized for Adverse Event (AE) reporting. A grading (severity) scale is provided for each AE term.

  6. Quality of life questionnaire - Core 30 (QLQ-C30) [ Time Frame: At baseline, 3 months, 6 months, every 6 months up to 5 years then every 12 months up to 10 years ]

    Developed by the EORTC, this self-reported questionnaire assesses the health-related quality of life of cancer patients in clinical trials.

    The questionnaire includes five functional scales (physical, everyday activity, cognitive, emotional, and social), three symptom scales (fatigue, pain, nausea and vomiting), a health/quality of life overall scale, and a number of additional elements assessing common symptoms (including dyspnea, loss of appetite, insomnia, constipation, and diarrhea), as well as, the perceived financial impact of the disease.

    All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level.


  7. Quality of Life Questionnaire - Prostate Cancer Module (QLQ-PR25) [ Time Frame: At baseline, 3 months, 6 months, every 6 months up to 5 years then every 12 months up to 10 years ]

    This EORTC prostate cancer specific questionnaire is intended to supplement the QLQ-C30.

    The prostate cancer module is a 25-item questionnaire designed for use among patients with localized and metastatic prostate cancer. It includes subscales assessing urinary symptoms (9 items), bowel symptoms (4 items), treatment-related symptoms (6 items) and sexual functioning (6 items). Using a 4-point Likert scale (1 = "not at all", 2 = "a little", 3 = "quite a bit", and 4 = "very much"), patients indicate the degree to which they have experienced symptoms.


  8. International Index of Erectile Function (IIEF-5) [ Time Frame: At baseline, 3 months, 6 months, every 6 months up to 5 years then every 12 months up to 10 years ]
    International Index of Erectile Function (IIEF-5) is multidimensional, self-administered questionnaire composed of 15 questions that examine the 4 main domains of male sexual function (erectile function [6 items], orgasmic function [2 items], sexual desire [2 items], and intercourse satisfaction [3 items]) and overall satisfaction (2 items). Using a 6-point Likert scale (questions 1 to 10) and 5-point Likert scale (questions 15 to 15), patients indicate the degree to which they have experienced symptoms. The total score for each domain can therefore classifies the severity of erectile dysfunction into five categories: no (score 26-30), mild (22-25), mild to moderate (17-21), moderate (11-16), and severe (1-10) erectile dysfunction.

  9. Lawton Instrumental Activities of Daily Living (IADL) Scale [ Time Frame: At baseline, 3 months, 6 months, every 6 months up to 5 years then every 12 months up to 10 years ]
    Lawton Instrumental Activities of Daily Living (IADL) Scale is a self-reported questionnaire to assess independent living skills for older adults. This questionnaire, composed of 31 questions organized into 8 domains (ability to use telephone, shopping, food preparation, housekeeping, laundering, mode of transportation, responsibility for own medications, and ability to handle finances), is designed to identify improvement or deterioration of a person functioning over time. Each domain is scored 0-1 for a summary score ranging from 0 (low function, dependent) to 8 (high function, independent).



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04181203


Locations
Layout table for location information
France
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
Sponsors and Collaborators
UNICANCER
Janssen Pharmaceutica
Investigators
Layout table for investigator information
Principal Investigator: Stéphane SUPIOT Institut de Cancérologie de l'Ouest - Saint Herblain
Layout table for additonal information
Responsible Party: UNICANCER
ClinicalTrials.gov Identifier: NCT04181203    
Other Study ID Numbers: UC-0160/1702
2017-000155-21 ( EudraCT Number )
First Posted: November 29, 2019    Key Record Dates
Last Update Posted: April 24, 2020
Last Verified: April 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by UNICANCER:
Apalutamide
Salvage radiotherapy
Radical prostatectomy
PSA
Additional relevant MeSH terms:
Layout table for MeSH terms
Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases
Leuprolide
Goserelin
Triptorelin Pamoate
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Fertility Agents, Female
Fertility Agents
Reproductive Control Agents
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Luteolytic Agents
Contraceptive Agents, Female
Contraceptive Agents