Primary ObjectiveTo determine if JNJ-56021927 plus gonadotropin releasing hormone (GnRH) agonist in subjects with high-risk, localized or locally advanced prostate cancer receiving primary radiation therapy (RT) results in an improvement of…
ID
Source
Brief title
Condition
- Prostatic disorders (excl infections and inflammations)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
EFFICACY EVALUATIONS/ENDPOINTS
To assess for distant metastasis, bone scan and chest, abdomen, and pelvis
computed tomography (CT) or magnetic resonance imaging (MRI) are required at
the time of BCF (Phoenix definition, 2 ng/mL increase in PSA over nadir) and
will continue as outlined in the Time and Events Schedule until documented
distant metastasis by BICR or death. All clinically indicated unscheduled
imaging must be reviewed by BICR. The primary endpoint of the study is MFS. The
secondary endpoints are the time to local-regional recurrence, time to CRPC,
time to distant metastasis, and OS.
Where possible, a PET scan must also be performed utilizing a prostate
cancer-specific tracer such as, for example, PSMA-targeting tracer,
18F-fluciclovine, or 11C-choline. Conventional imaging must continue every 6
months (±4 weeks) until documented distant metastasis by BICR or death. PET
will be performed and repeated at the same interval as conventional imaging
until either the PET scan reveals distant metastases per local review, or BICR
of conventional imaging indicates distant metastasis, whichever occurs first. In
the event that the PET scan reveals distant metastases and the BICR of
conventional imaging does not, conventional imaging must be continued every
6 months until distant metastasis are seen by BICR.
The PROs included in this study are the FACT-P and the EQ-5D-5L. These
questionnaires will be completed at the time points specified in the Time and
Events Schedule.
Secondary outcome
PHARMACOKINETIC EVALUATIONS
Population PK assessments will be performed on approximately 750 subjects.
Pre-dose blood samples for population PK will be collected as described in the
Laboratory Manual.
BIOMARKER EVALUATIONS
Archival formalin-fixed paraffin-embedded (FFPE) tumor blocks or slides will be
collected from all subjects consenting to genomic research to evaluate
expression of high-risk markers and molecular classifiers such as OncotypeDx.
Androgen-receptor splice variant 7 (AR-V7) expression and ARF876L levels will
be evaluated.
MEDICAL RESOURCE UTILIZATION AND HEALTH ECONOMICS
Duration of medical care encounters, duration of hospitalization, the number
and type of diagnostic and therapeutic tests and procedures, and outpatient
medical encounters and treatments will be collected and may be used to conduct
exploratory economic analyses.
Background summary
JNJ-56021927 (also referred to as ARN-509) is an orally available,
non-steroidal selective antagonist of the androgen receptor (AR). JNJ-56021927
directly antagonizes the binding of androgen to the ligand-binding domain of
the AR, impairing nuclear translocation and DNA binding. JNJ-56021927 binds the
AR with 5-fold greater affinity than the first-generation anti-androgen
bicalutamide. JNJ-56021927 is currently being developed for the treatment of
both hormone-sensitive and castration-resistant prostate cancer (CRPC).
Patients with high- or very high-risk, localized or locally advanced prostate
cancer include those with Gleason scores >=8, clinical stage >=cT2c (disease in
both or extension outside of the lobes), high baseline PSA (>=20 ng/mL), or
involvement of regional nodes. These patients are more likely to develop
metastatic disease than are low- or intermediate-risk patients.
Patients with high-risk localized or locally advanced prostate cancer who
undergo primary radiation therapy (RT) for the treatment of prostate cancer are
commonly older and have more comorbidities than those who undergo radical
prostatectomy. Although these patients have a significant prostate
cancer-specific mortality risk, they may also have a high risk of mortality
from other causes within 10 years of the diagnosis. Algorithms such as the
Charlson Comorbidity Index (CCI), which is based on age and other
comorbidities, may be utilized to select patients who will have a low 10-year
probability of death from competing causes. Combined, the protocol-defined
high-risk disease selection criteria and a >10-year life expectancy (based on
the CCI) will identify those who are most likely to derive benefit from primary
RT and long-term androgen deprivation therapy (ADT).
Multiple studies have shown that the addition of long-term ADT (gonadotropin
releasing hormone [GnRH] agonist +/- anti-androgen) to RT delays disease
progression (ie, local-regional recurrence or distant metastasis) and prolongs
survival. Thus, the National Comprehensive Cancer Network (NCCN, category 1)
and European Association of Urology (EAU Level 1b) recommend RT combined with 2
or 3 years of ADT. Despite the use of ADT in combination with RT, metastatic
progression and prostate cancer-related death still occur frequently in
patients with high-risk disease. Therefore, high-risk, localized and locally
advanced prostate cancer represents a serious clinical problem with currently
unmet treatment needs.
Prostate cancer cells depend on AR signaling for DNA repair after damage from
irradiation and the addition of a GnRH agonist plus a first generation
anti-androgen, bicalutamide to RT improves outcomes. Therefore, it is
hypothesized that a more complete AR blockade with the AR antagonist,
JNJ-56021927, plus GnRH agonist will further delay time to distant metastasis
and prostate cancer-related death in patients with high-risk localized or
locally advanced prostate cancer receiving RT.
Study objective
Primary Objective
To determine if JNJ-56021927 plus gonadotropin releasing hormone (GnRH) agonist
in subjects with high-risk, localized or locally advanced prostate cancer
receiving primary radiation therapy (RT) results in an improvement of
metastasis-free survival (MFS) evaluated by blinded independentcentral review
(BICR)
Secondary Objectives
-To characterize the safety profile of JNJ-56021927 plus GnRH agonist in
subjects with high-risk, localized or locally advanced prostate cancer
receiving primary RT
-To determine if JNJ-56021927 plus GnRH agonist in subjects with high-risk,
localized or locally advanced prostate cancer receiving primary RT results in
an improvement of:
o Event-free survival
o Time PSA progression
o Overall survival (OS)
o Time to distant metastasis
o Time to next local or systematic treatment
o MFS by conventional or PET imgaging.
Other Objectives
-To determine if JNJ-56021927 plus GnRH agonist in subjects with high-risk,
localized or locally advanced prostate cancer receiving primary RT delays the
development of:
o Skeletal-related events (SREs)
o Disease progression-related pain
o Biochemical failure (BCF)
o Progression/ relapse on or after the next line of treatment
o Time to local-regional recurrence
o Time to castration-resistant prostate cancer (CRPC)
- To evaluate the effect of JNJ-56021927 plus GnRH agonist in subjects with
high-risk, localized or locally advanced prostate cancer receiving primary RT
on the normalization of testosterone
- To evaluate the effect of JNJ-56021927 plus GnRH agonist in subjects with
high-risk, localized or locally advanced prostate cancer receiving primary RT
on patient relevant outcomes including symptoms, function, and health-related
quality of life
- To characterize the population pharmacokinetics (PK) of JNJ-56021927
- To demonstrate the cost benefit of JNJ-56021927 plus GnRH agonist compared
with GnRH agonist in subjects with high-risk, localized or locally advanced
prostate cancer receiving primary RT
- To evaluate the effect on PSA response of JNJ-56021927 plus GnRH agonist
compared with GnRH agonist in subjects with high-risk, localized or locally
advanced prostate cancer receiving primary RT
- To evaluate potential biomarkers predictive of response and resistance to
JNJ-56021927 treatment
- To determine the proportion of patients with no PSA progression at 12,24,26,
and 48 months
- To determine the proportion of patients with no evidence of disease (NED) at
4 years
- To determine the proportion of patients developing androgen receptor (AR)
resistance based upon clinical, pathological, or molecular markers.
Study design
This is a randomized, double-blind, placebo-controlled, multicenter study of
JNJ-56021927 plus GnRH agonist compared with GnRH agonist in subjects with
high-risk, localized or locally advanced prostate cancer receiving primary RT.
All subjects will receive active treatment with a GnRH agonist and primary RT
as standard of care. Approximately 1,500 subjects will be randomly assigned in
a 1:1 ratio to receive JNJ-56021927 or control. Randomization will be
stratified by Gleason score (7 or >=8), N0 or N1, brachytherapy boost (yes or
no), and region (NA, EU, or Other Countries).
The study will include a Screening Phase, Treatment Phase, a Posttreatment
Phase and a Long-term Follow-up Phase.
The Screening Phase will allow for assessment of subject eligibility,
demographics, PSA, and testosterone up to 35 days prior to randomization.
The Treatment Phase will include 30 cycles of therapy (each cycle is 28 days).
All subjects will receive GnRH agonist therapy throughout the Treatment Phase:
- Neoadjuvant to primary RT (2, 28-day cycles [Cycle 1, Day 1; C1D1 to C2D28])
o Investigational group will receive JNJ-56021927 plus bicalutamide placebo
daily
o Control group will receive bicalutamide plus JNJ-56021927 placebo daily
- Concurrent with primary RT (2, 28-day cycles [C3D1 to C4D28])
o Investigational group will receive JNJ-56021927 plus bicalutamide placebo
daily
o Control group will receive bicalutamide plus JNJ-56021927 placebo daily
- Adjuvant to primary RT (26, 28-day cycles [C5D1 to C30D28])
o Investigational group will receive JNJ-56021927 daily
o Control group will receive JNJ-56021927 placebo daily
The Posttreatment Phase will begin after a subject completes the Treatment
Phase and the
End-of-Treatment Visit. The Posttreatment Phase will continue until documented
distant metastasis by BICR, death, lost to follow-up, withdrawal of consent or
termination of the study by the sponsor, whichever occurs first.
The Long-term Follow-up Phase will begin after a subject completes the
Posttreatment Phase and End-of-Posttreatment Phase Visit. The Long-term
Follow-up Phase will continue until death, lost to follow-up, withdrawal of
consent or termination of the study by the sponsor, whichever occurs first.
An Independent Data Monitoring Committee (IDMC) will be commissioned for this
study. The IDMC will review the safety and efficacy data during the study and
make recommendations as to the further conduct of the study.
Intervention
An Independent Data Monitoring Committee (IDMC) will be commissioned for this
study. The IDMC will review the safety and efficacy data during the study and
make recommendations as to the further conduct of the study.
Study burden and risks
Safety evaluations will include adverse events (AEs) (incidence, intensity, and
type), vital sign measurements, clinical laboratory test results, and limited
physical examinations.
Bond Park Graaf Engelbertlaan 75
Breda 4837 DS
NL
Bond Park Graaf Engelbertlaan 75
Breda 4837 DS
NL
Listed location countries
Age
Inclusion criteria
- Age >=18 years
- Indicated and planned to receive primary radiation therapy for prostate cancer
-Histologically confirmed adenocarcinoma of an intact prostate, and 1 of the
following at
diagnosis:
• Gleason score >=8 and >=cT2c stage per AJCC 8th Edition
• Gleason score 7, PSA >=20 ng/mL, and >=cT2c stage per AJCC
- Charlson comorbidity index (CCI) <=3
- An Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) grade of
0 or 1
- Adequate liver function: aspartate aminotransferase (AST), alanine
aminotransferase (ALT), <2 x upper limit of normal (ULN) and total bilirubin
<1.5 x ULN
- Participants who are sexually active (even men with vasectomies) and willing
to use a condom and agree not to donate sperm during the trial
- Signed, written, informed consent
- Be able to swallow whole study drug tablets
Exclusion criteria
- Presence of distant metastasis, including pelvic nodal disease below the
iliac bifurcation >2 cm in the short axis
- Prior treatment with GnRH analogue or antiandrogen or both for >3 months
prior to randomization
- Bilateral orchiectomy
- History of pelvic radiation
- Prior systemic (eg, chemotherapy) or procedural (eg, prostatectomy,
cryotherapy) treatment for prostate cancer
- 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)
- Prior treatment with enzalutamide, abiraterone acetate, orteronel,
galeterone, ketoconazole, aminoglutethimide, estrogens, megestrol acetate, and
progestational agents for prostate cancer
- Prior treatment with radiopharmaceutical agents (eg, strontium 89) or
immunotherapy (eg, sipuleucel-T) for prostate cancer
- 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 5-alpha reductase inhibitors (eg, dutasteride, finasteride) <=4 weeks
prior to randomization
- 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
- Current or prior treatment with antiepileptic medications for the treatment
of seizures
- Gastrointestinal conditions affecting absorption
- Known or suspected contraindications or hypersensitivity to JNJ-56021927,
bicalutamide or 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
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2015-003007-38-NL |
| CCMO | NL55777.078.15 |