Clinical trial NCT03488810: Apalutamide With Radiotherapy and Androgen Deprivation Therapy in Prostate Cancer
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
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE3
Conditions: Prostate Cancer
Keywords: Apalutamide Prostate Cancer Radiotherapy
Lead sponsor: European Organisation for Research and Treatment of Cancer - EORTC
Sponsor class: NETWORK
First posted: 2018-04-05
Enrollment: 0
Sex: MALE
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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

Primary outcomes:
measure: Disease-free survival
timeFrame: 7.8 years from First Patient In (FPI)
Secondary outcomes:
measure: Progression-free survival
timeFrame: 7.8 years from First Patient In (FPI)
measure: Distant Metastasis-free survival
timeFrame: 7.8 years from First Patient In (FPI)
measure: Overall survival
timeFrame: 7.8 years from First Patient In (FPI)
measure: Prostate cancer specific survival
timeFrame: 7.8 years from First Patient In (FPI)
measure: Prostate-Specific Antigen (PSA) value
timeFrame: 5.5 years from First Patient In (FPI)
measure: Adverse events graded according to the National Cancer Institute Common Occurrence of Adverse Events
timeFrame: 7.8 years from First Patient In (FPI)
measure: Health-related quality of life
timeFrame: 7.8 years from First Patient In (FPI)
measure: Health-related quality of life
timeFrame: 7.8 years from First Patient In (FPI)
measure: Prostate-Specific Antigen (PSA) nadir
timeFrame: 5.5 years from First Patient In (FPI)
Other outcomes:
Locations:
Study officials:
affiliation: Centre Georges Francois Leclerc
name: Gilles Crehange
role: PRINCIPAL_INVESTIGATOR
affiliation: CHU de Grenoble - La Tronche - Hôpital A. Michallon, France
name: Michel Bolla
role: PRINCIPAL_INVESTIGATOR
References: