Apalutamide With Radiotherapy and Androgen Deprivation Therapy in Prostate Cancer

NCT03488810 | Withdrawn Phase 3

• 1 other identifier: EORTC-1531-ROG
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Prostate Cancer

Keywords

Apalutamide Prostate Cancer Radiotherapy

Outcome Measures

Primary Outcomes (1)

• Disease-free survival

  Events for this endpoint include loco-regional recurrence, distant metastases (radiologically or pathologically confirmed), death from any cause, whichever occurs first

  7.8 years from First Patient In (FPI)

Secondary Outcomes (9)

• Progression-free survival

  7.8 years from First Patient In (FPI)

• Distant Metastasis-free survival

  7.8 years from First Patient In (FPI)

• Overall survival

  7.8 years from First Patient In (FPI)

• Prostate cancer specific survival

  7.8 years from First Patient In (FPI)

• Prostate-Specific Antigen (PSA) value

  5.5 years from First Patient In (FPI)

Study Arms (2)

Arm A: ADT + radiation therapy

ACTIVE COMPARATOR

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; Drug: Luteinising Hormone Releasing Hormone analog agonist (LHRHa); Drug: Non-steroidal anti-androgen

Arm B: ADT + radiation therapy + Apalutamide

EXPERIMENTAL

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; Drug: Apalutamide; Drug: Luteinising Hormone Releasing Hormone analog agonist (LHRHa)

Interventions

Radiation Therapy OTHER

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

Arm A: ADT + radiation therapy; Arm B: ADT + radiation therapy + Apalutamide

Apalutamide DRUG

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

Arm B: ADT + radiation therapy + Apalutamide

Luteinising Hormone Releasing Hormone analog agonist (LHRHa) DRUG

2 injections of a three-monthly LHRH agonist depot

Arm A: ADT + radiation therapy; Arm B: ADT + radiation therapy + Apalutamide

Non-steroidal anti-androgen DRUG

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

Arm A: ADT + radiation therapy

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• European Organisation for Research and Treatment of Cancer - EORTC: lead

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

Radiotherapy; apalutamide

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)

Therapeutics

Study Officials

• Gilles Crehange

  Centre Georges Francois Leclerc

  PRINCIPAL INVESTIGATOR

• Michel Bolla

  CHU de Grenoble - La Tronche - Hôpital A. Michallon, France

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: March 27, 2018
• First Posted: April 5, 2018
• Study Start: March 10, 2020
• Primary Completion (Estimated): June 15, 2026
• Study Completion (Estimated): June 15, 2026
• Last Updated: August 17, 2020

Record last verified: 2020-08