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Trial record 49 of 1543 for:    Androgens

Apalutamide With Radiotherapy and Androgen Deprivation Therapy in Prostate Cancer (ARN-509)

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ClinicalTrials.gov Identifier: NCT03488810
Recruitment Status : Not yet recruiting
First Posted : April 5, 2018
Last Update Posted : July 12, 2018
Sponsor:
Information provided by (Responsible Party):
European Organisation for Research and Treatment of Cancer - EORTC

Brief Summary:
The main objective of the trial to determine if the combination of apalutamide with 6 months of androgen deprivation therapy by LHRH agonists in patients with intermediate and limited high-risk, localized prostate cancer receiving primary radiation therapy (RT) results in an improvement of disease-free survival (DFS) evaluated by the treating physician, in comparison to the combination of radiation and androgen deprivation therapy without the addition of apalutamide.

Condition or disease Intervention/treatment Phase
Prostate Cancer Other: Radiation Therapy Drug: Apalutamide Drug: Luteinising Hormone Releasing Hormone analog agonist (LHRHa) Drug: Non-steroidal anti-androgen Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 990 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Radiotherapy and 6-month Androgen Deprivation Therapy With or Without Apalutamide in Intermediate and Limited High Risk Localized Prostate Cancer: a Phase III Study
Estimated Study Start Date : August 1, 2018
Estimated Primary Completion Date : June 15, 2026
Estimated Study Completion Date : June 15, 2026

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Prostate Cancer
Drug Information available for: Apalutamide

Arm Intervention/treatment
Active Comparator: Arm A: ADT + radiation therapy

Patient will receive 2 injections of a three-monthly LHRH agonist depot plus non-steroidal anti-androgen (rescue treatment) (e. g. flutamide, bicalutamide) PO daily for 4 weeks, started 2 weeks before the first LHRH agonist injection.

All patients will receive standard fractionation radiation therapy (RT) between 0 and 12 weeks after first injection of LHRH agonist.

Other: Radiation Therapy
Dose escalated Intensity-Modulated Radiation therapy (IMRT) with conventional fractionation, hypofractionation and prostate brachytherapy are allowed.

Drug: Luteinising Hormone Releasing Hormone analog agonist (LHRHa)
2 injections of a three-monthly LHRH agonist depot

Drug: Non-steroidal anti-androgen
Non-steroidal anti-androgen (e. g. flutamide, bicalutamide) PO daily for 4 weeks, started 2 weeks before the first LHRH agonist injection

Experimental: Arm B: ADT + radiation therapy + Apalutamide

Patients will receive 2 injections of a three-monthly LHRH agonist depot. Apalutamide treatment: 240 mg PO daily, started the same day as the first LHRHa injection, for 6 months.

All patients will receive standard fractionation radiation therapy (RT) between 0 and 12 weeks after first injection of LHRH agonist.

Other: Radiation Therapy
Dose escalated Intensity-Modulated Radiation therapy (IMRT) with conventional fractionation, hypofractionation and prostate brachytherapy are allowed.

Drug: Apalutamide
240 mg PO daily, started the same day as the first LHRHa injection, for 6 months

Drug: Luteinising Hormone Releasing Hormone analog agonist (LHRHa)
2 injections of a three-monthly LHRH agonist depot




Primary Outcome Measures :
  1. Disease-free survival [ Time Frame: 7.8 years from First Patient In (FPI) ]
    Events for this endpoint include loco-regional recurrence, distant metastases (radiologically or pathologically confirmed), death from any cause, whichever occurs first


Secondary Outcome Measures :
  1. Progression-free survival [ Time Frame: 7.8 years from First Patient In (FPI) ]
    includes first events of biochemical failure by Phoenix criteria in addition to the events listed in the primary endpoint DFS

  2. Distant Metastasis-free survival [ Time Frame: 7.8 years from First Patient In (FPI) ]
  3. Overall survival [ Time Frame: 7.8 years from First Patient In (FPI) ]
  4. Prostate cancer specific survival [ Time Frame: 7.8 years from First Patient In (FPI) ]
  5. Prostate-Specific Antigen (PSA) value [ Time Frame: 5.5 years from First Patient In (FPI) ]
    Prostate-Specific Antigen (PSA) value will be assessed at the end of the treatment of each patient

  6. Adverse events graded according to the National Cancer Institute Common Occurrence of Adverse Events [ Time Frame: 7.8 years from First Patient In (FPI) ]
    Adverse events will be graded according to the National Cancer Institute Common Terminology Criteria for adverse events (NCI-CTCAE) version 4.0

  7. Health-related quality of life [ Time Frame: 7.8 years from First Patient In (FPI) ]
    Health-related quality of life will be evaluated using self-administered EORTC QLQ-C30 questionnaire

  8. Health-related quality of life [ Time Frame: 7.8 years from First Patient In (FPI) ]
    Health-related quality of life will be evaluated using EORTC QLQ-PR25 instruments

  9. Prostate-Specific Antigen (PSA) nadir [ Time Frame: 5.5 years from First Patient In (FPI) ]
    Prostate-Specific Antigen (PSA) nadir will be assessed as the lowest value achievement on treatment



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

Inclusion Criteria:

  • Histologically confirmed diagnosis of prostate adenocarcinoma diagnosed by ultrasound guided biopsy of the prostate containing 10-12 cores showing no neuroendocrine component
  • Either of: Favorable intermediate risk (according to EAU risk groups): PSA 10-20 ng/mL, -or Gleason score 7 (3 +4) (ISUP Grade 2), or cT2b. Infavorable intermediate risk (according to EAU risk groups): PSA 10-20 ng/mL, -or Gleason score 7 (4+3) (ISUP Grade 3), or cT2b. Limited high risk : PSA > 20 ng/mL or Gleason score >7 (ISUP Grade 4/5)
  • M0 by standard imaging work-up
  • Scheduled to be treated with primary prostate RT
  • WHO Performance Status ≤ 2
  • No risk of urinary retention based on the International Prostate Symptom Score (IPSS) : IPSS < 20
  • Adequate liver function determined by the following: aspartate aminotransferase (AST), alanine aminotransferase (ALT), < 2.5 x upper limit of normal (ULN). Total bilirubin <1.5 x upper limit of normal (ULN)
  • Adequate renal function: creatinine level < 2 x ULN
  • Serum albumin ≥ 3.0 g/dL
  • Serum potassium ≥ 3.5 mmol/L
  • Hemoglobin ≥ 10.0 g/dL, independent of transfusion and/or growth factors within 3 months prior to randomization
  • Platelet count ≥ 100,000 x 109/L independent of transfusion and/or growth factors within 3 months prior to randomization
  • Be able to swallow whole study drug tablets

Exclusion Criteria:

  • cT2c, T3, T4 or pelvic lymph nodes involvement, as assessed by CT scan or MRI (cN1) or pelvic lymph node dissection (pN1)
  • Previous pelvic irradiation or radical prostatectomy.
  • Bilateral orchiectomy
  • Prior systemic (e.g., chemotherapy) or procedural (e.g., prostatectomy, cryotherapy) treatment for prostate cancer
  • Prior treatment with 5-alpha reductase inhibitors for benign prostatic hypertrophy not discontinued 4 weeks prior to randomization
  • Prior treatment with any LHRH agonist or antagonist, bicalutamide, flutamide or nilutamide, enzalutamide, abiraterone acetate, orteronel, galeterone, ketoconazole, aminoglutethimide, estrogens, megestrol acetate, and progestational agents for prostate cancer
  • Prior treatment with radiopharmaceutical agents (e.g., strontium-89) or immunotherapy for prostate cancer
  • 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.
  • History of Ulcerative Colitis, Crohn's Disease, Ataxia Telangiectasia, systemic lupus erythematosus or Fanconi anemia
  • History of seizure or condition that may predispose 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 thresholdmust be discontinued or substituted at least 4 weeks prior to study entry
  • 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 > 450 ms at baseline
  • Uncontrolled hypertension (systolic 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
  • Bilateral hip prostheses
  • Prior treatment with systemic glucocorticoids ≤ 4 weeks prior to randomization or is expected to require long-term use of corticosteroids during the study
  • Use of any investigational agent ≤ 4 weeks prior to randomization
  • Current chronic use of opioid analgesics for ≥3 weeks for oral or ≥ 7 days for non-oral formulations
  • Major surgery ≤ 4 weeks prior to randomization
  • Known or suspected contraindications or hypersensitivity to apalutamide, bicalutamide or LHRHa agonists or any of the components of the formulations
  • Presence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial

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): NCT03488810


Contacts
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Contact: EORTC HQ +32 2 7744 1611 1531@eortc.org

Locations
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Switzerland
Inselspital Not yet recruiting
Bern, Switzerland, 3010
Principal Investigator: Daniel Aebersold         
Hôpitaux universitaires de Genève - HUG - site de Cluse-Roseraie Not yet recruiting
Geneve, Switzerland, 1211
Principal Investigator: Thomas Zilli         
Clinique De Genolier Not yet recruiting
Genolier, Switzerland, 1272
Principal Investigator: Jean-Claude Horiot         
Kantonsspital St Gallen Not yet recruiting
Saint Gallen, Switzerland, 9007
Principal Investigator: Paul Martin Putora         
UniversitaetsSpital Zurich Not yet recruiting
Zürich, Switzerland, 8091
Principal Investigator: Matthias Guckenberger         
Sponsors and Collaborators
European Organisation for Research and Treatment of Cancer - EORTC
Investigators
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Principal Investigator: Gilles Crehange Centre Georges Francois Leclerc
Principal Investigator: Michel Bolla CHU de Grenoble - La Tronche - Hôpital A. Michallon, France

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Responsible Party: European Organisation for Research and Treatment of Cancer - EORTC
ClinicalTrials.gov Identifier: NCT03488810     History of Changes
Other Study ID Numbers: EORTC-1531-ROG
First Posted: April 5, 2018    Key Record Dates
Last Update Posted: July 12, 2018
Last Verified: July 2018

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by European Organisation for Research and Treatment of Cancer - EORTC:
Apalutamide Prostate Cancer Radiotherapy
Additional relevant MeSH terms:
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Androgens
Androgen Antagonists
Nonsteroidal Anti-Androgens
Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases
Ascorbic Acid
Methyltestosterone
Hormones
Estrogens, Conjugated (USP)
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antioxidants
Molecular Mechanisms of Pharmacological Action
Protective Agents
Vitamins
Micronutrients
Nutrients
Growth Substances
Estrogens
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Anabolic Agents
Hormone Antagonists