A study of androgen deprivation therapy (ADT) plus apalutamide (with or without abiraterone acetate with prednisone/prednisolone [AAP]) in patients with prostate cancer

Phase 1

• Conditions: High-risk localized or locally advanced prostate cancer; MedDRA version: 20.0Level: PTClassification code 10060862Term: Prostate cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2018-001746-34-FR
• Lead Sponsor: Janssen-Cilag International NV

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2018-11-14
• Last Update Posted: 2 June 2020

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: Male
• Target Recruitment: 1500

Inclusion Criteria

1. Must be =18 years of age
2. Signed an informed consent form (ICF) indicating that the subject understands the purpose of and procedures required for the study and is willing to participate in the study; subjects must be willing and able to adhere to the prohibitions and restrictions specified in this protocol (Section 4.3)
3. Histologically confirmed adenocarcinoma of the prostate
4. High risk defined by =1 of the following 4 criteria:
• Any combination of Gleason score 4+3 and 4+4 from =6 systematic cores
• Any combination of Gleason score 4+3 and 4+4 from =3 systematic cores and PSA =20 ng/mL
• Gleason score =9 in at least one systematic or targeted core
• At least 2 systematic or targeted cores with continuous Gleason score =8, each with = 80% involvement
5. Candidate for radical prostatectomy as per the investigator
6. Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1
7. Adequate organ function determined by the following central laboratory values:
a. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and total bilirubin less than the upper limit of normal (ULN; note that in subjects with Gilbert’s syndrome, if total bilirubin is >1.5 X ULN, measure direct and indirect bilirubin. If direct bilirubin is =1.5 X ULN, the subject may be eligible)
b. Serum creatinine <1.5 mg/dL
c. Platelets =75,000/uL, without transfusion and/or growth factors within 1 month prior to randomization
d. Hemoglobin =12.0 g/dL (7.4 mmol), without transfusion and/or growth factors within 1 month prior to randomization
8. Able to receive ADT for up to 1 year, per the investigator’s assessment
9. Be able to swallow whole study drug tablets and capsules
10. Contraceptive (birth control) use by men (or female partners of men enrolled in the study who are of childbearing potential or are pregnant) should be consistent with local regulations regarding the acceptable methods of contraception for those participating in clinical studies.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 1200
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 300

Exclusion Criteria

1. Distant metastasis (clinical stage M1). Nodal disease below the iliac bifurcation (clinical stage N1) is not an exclusion. Diagnosis of distant metastasis (clinical M stage; M0 versus M1a, M1b, M1c) and pelvic nodal disease (clinical N stage; N1 versus N0) will be assessed by central radiological review. Patients are considered eligible only if the central radiological review confirms clinical stage M0
2. Prior treatment with anti-androgen
3. Prior treatment for prostate cancer
4. Pathological finding consistent with small cell, ductal or neuroendocrine carcinoma of the prostate
5. Bilateral orchiectomy
6. History of any pelvic radiation
7. Use of any investigational agent =4 weeks prior to randomization
8. Major surgery =4 weeks prior to randomization
9. Any of the following within 6 months prior to first dose of study drug: severe or unstable angina, myocardial infarction, symptomatic congestive heart failure, arterial or venous thromboembolic events (eg, pulmonary embolism, cerebrovascular accident including transient ischemic attacks), or clinically significant ventricular arrhythmias or New York Heart Association Class II to IV heart disease; uncomplicated deep vein thrombosis is not considered exclusionary
10. Human immunodeficiency virus-positive subjects with 1 or more of the following:
a. Not receiving highly active antiretroviral therapy
b. Had a change in antiretroviral therapy within 6 months of the start of screening
c. Receiving antiretroviral therapy that may interfere with study drug (consult sponsor for review of medication prior to enrollment)
d. CD4 count <350 at screening
e. AIDS-defining opportunistic infection within 6 months of start of screening
11. Active or symptomatic viral hepatitis or chronic liver disease; ascites or bleeding disorders secondary to hepatic dysfunction
12. History of seizure or any 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)
13. Treatment with drugs known to lower the seizure threshold within 4 weeks prior to randomization
14. Gastrointestinal conditions affecting absorption
15. Known or suspected contraindications or hypersensitivity to apalutamide, abiraterone acetate, GnRH agonists or any of the components of the formulations
16. Any condition for which, in the opinion of the investigator, participation would not be in the best interest of the subject

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified