A Randomized, Double-blind, Placebo-controlled, Phase III Study of Apalutamide in Subjects With High-risk, Localized or Locally Advanced Prostate Cancer Who Are Candidates for Radical Prostatectomy.
Study Identifier:
56021927PCR3011
CT.gov Identifier:
EudraCT Identifier:
EU Trial (CTIS) Number:
Study Contact Information:
Recruitment Complete
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Study Summary
To determine if treatment with androgen deprivation therapy (ADT) plus apalutamide before and after radical prostatectomy in participants with high-risk localized or locally advanced prostate cancer results in an improvement in pathological complete response (pCR) rate and metastasis-free survival (MFS), as compared to ADT plus placebo.
To determine if treatment with APA + ADT before RP in pts with localized high-risk or locally advanced PC improves pathologic complete response (pCR) rate and if neoadjuvant and adjuvant peri-operative treatment with APA + ADT improves metastasis-free survival (MFS) compared with PBO + ADT
To examine if 12 months of perioperative APA + ADT tx before and after RP with pelvic lymph node dissection (pLND) in localized/locally advanced high-risk PC improves pathologic complete response (pCR) rate and metastasis-free survival (MFS) vs PBO + ADT.
Medical Condition
The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.
Phase
The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
III
Sex
Male
Age
18+ years
Study Drug
Study Status
Indicates the current recruitment status or the expanded access status
Recruitment Complete
Requirements information
Inclusion criteria
- Histologically confirmed adenocarcinoma of the prostate
- High-risk disease defined by a total Gleason Sum Score greater than equal to (>=) 4+3 (=Grade Groups [GG] 3-5) and >=1 of the following 4 criteria: a) Any combination of Gleason Score 4+3 (= 3) and Gleason Score 8 (4+4 or 5+3) in >= 6 systematic cores (with >=1 core Gleason Score 8 [4+4 or 5+3] included); b) Any combination of Gleason Score 4+3 (=GG 3) and Gleason Score 8 (4+4 or 5+3) in >=3 systematic cores and Prostate-specific antigen (PSA) >=20 ng/mL (with >= 1 core Gleason Score 8 [4+4 or 5+3] included); c) Gleason Score >=9 (=GG 5) in at least 1 systematic or targeted core; d) At least 2 systematic or targeted cores with continuous Gleason Score >=8 (=GG 4), each with > 80 percent (%) involvement
- Candidate for radical prostatectomy with pelvic lymph node dissection as per the investigator
- Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1
- Contraceptive use by male participants (and female partners of male participants enrolled in the study who are of childbearing potential or are pregnant) should be consistent with local regulations regarding the use of contraceptive methods for participants participating in clinical studies
- Able to receive androgen deprivation therapy (ADT) for at least 13 months
- Must be > or = 18 years of age
- 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)
- High risk defined by > or =1 of the following 4 criteria:
- Any combination of Gleason score 4+3 and 4+4 from > or =6 systematic cores
- Any combination of Gleason score 4+3 and 4+4 from > or =3 systematic cores and PSA > or = 20 ng/mL
- Gleason score > or = 9 in at least one systematic or targeted core
- At least 2 systematic or targeted cores with continuous Gleason score > or = 8, each with > or = 80% involvement
- Candidate for radical prostatectomy as per the investigator
- 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 < or = 1.5 X ULN, the subject may be eligible)
- Serum creatinine <1.5 mg/dL
- Platelets > or = 75,000/uL, without transfusion and/or growth factors within 1 month prior to randomization
- Hemoglobin > or =12.0 g/dL (7.4 mmol), without transfusion and/or growth factors within 1 month prior to randomization
- Be able to swallow whole study drug tablets and capsules
- Criterion modified per GBR-1:
- Any combination of Gleason score (GS) 4 + 3 ( = Grade Group [GG] 3) and GS 8 (4 + 4 or 5 + 3) from > or = 6 systematic biopsy cores (SB) or targeted biopsy cores (TB) (with > or = 1 core GS 8 [4 + 4 or 5 + 3] included); any combination of GS 4 + 3 ( = GG 3) and GS 8 (4 + 4 or 5 + 3) from > or = 3 SB or TB (with > or = 1 core GS 8 [4 + 4 or 5 + 3]) included and prostate-specific antigen (PSA) > or = 20 ng/mL; GS > or = 9 (GG 5) in > or = 1 SB or TB; or > or = 2 SB or TB with continuous GS > or = 8 (GG 4), each with > or = 80% involvement.
Exclusion criteria
- 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. Participants are considered eligible only if the central radiological review confirms clinical stage M0
- (a) Prior treatment with androgen receptor antagonists; (b) Treatment with gonadotropin-releasing hormone (GnRH) analogs prior to informed consent form (ICF) signature
- History of prior systemic or local therapy for prostate cancer, including pelvic radiation for prostate cancer
- Use of any investigational agent less than or equals to (< or =)4 weeks prior to randomization or any therapeutic procedure for prostate cancer at any time
- Major surgery < or = 4 weeks prior to randomization
- Prior treatment for prostate cancer
- Pathological finding consistent with small cell, ductal or neuroendocrine carcinoma of the prostate
- Bilateral orchiectomy
- 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
- 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
- Active or symptomatic viral hepatitis or chronic liver disease; ascites or bleeding disorders secondary to hepatic dysfunction
- 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 < or = 1 year prior to randomization; brain arteriovenous malformation; or intracranial masses such as schwannomas and meningiomas that are causing edema or mass effect)
- Treatment with drugs known to lower the seizure threshold within 4 weeks prior to randomization
- Gastrointestinal conditions affecting absorption
- Known or suspected contraindications or hypersensitivity to apalutamide, abiraterone acetate, GnRH agonists or any of the components of the formulations
- Any condition for which, in the opinion of the investigator, participation would not be in the best interest of the subject
- Any of the following within 12 months prior to first dose of study drug: severe or unstable angina, myocardial infarction, symptomatic congestive heart failure, arterial or venous thromboembolic events (example, 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
Clinical Study Information for Healthcare Providers
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Study Locations
Location
Investigator
Status
Condition(s) Treated at Site
Location
START Carolinas
Myrtle Beach, SC, United States, 29572
Investigator
Neal Shore
Status
Recruitment Complete
Condition(s) Treated at Site
Prostate