This study has been transitioned to CTIS with ID 2023-508606-26-00 check the CTIS register for the current data. Primary Objective:The primary objective is to compare the radiographic progression-free survival (rPFS) ofapalutamide in combination…
ID
Source
Brief title
Condition
- Reproductive neoplasms male malignant and unspecified
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Radiographic progression-free survival is defined as the time from date of
randomization to the date of radiographic progression or death, whichever
occurs first. Radiographic progression will be assessed by the investigator
based on soft tissue lesion by CT/MRI per modified Response Evaluation Criteria
in Solid Tumors (RECIST 1.1) or by bone lesion progression on bone scans per an
adaption of
the Prostate Clinical Trials Cancer Working Group 2 (PCWG2).
POPULATION PHARMACOKINETIC EVALUATIONS
Pharmacokinetic assessment will be conducted on as many subjects as feasible
(at least 200). Two separate blood samples will be collected at approximately
the same time for each sampling time point; 1 for abiraterone and 1 for
JNJ-56021927. On Day 1 of Cycle 1, blood samples will be collected at 2 hours
and 4 hours post the first dose for each subject. On Day 1 of Cycle 3, a
predose sample (up to 1 hour prior to on-site study drugs administration) and
postdose samples between 0.5 and 4 hours will be collected. For the other PK
visits (Cycles 2, 4, 5, and 6), blood samples will be collected predose (up to
1 hour prior to on-site study drugs administration).
BIOMARKER EVALUATIONS
Archived tumor samples (formalin-fixed paraffin-embedded [FFPE] blocks or
slides) and serum samples will be collected for biomarker evaluations. Plasma
samples will be collected from approximately 220 subjects during treatment and
approximately 500 subjects at the end-of-treatment or progression; whole blood
and serum will be collected from approximately 220 subjects at the time points
indicated in the Time & Events Schedule. Plasma-based circulating DNA will be
used to assess the presence of the ARF876L mutation and whole blood or plasma
DNA to assess other markers that may be associated with resistance to AA alone
and in combination with JNJ-56021927. Serum samples will be collected to
compare the effect of testosterone and steroid metabolites when subjects are
treated with AAP alone and in combination with JNJ 56021927. Archival FFPE
tumor blocks or tumor slides will be collected from at least 300 subjects in
this study to investigate whether genomic classifiers can be used to identify a
more homogeneous population of high-risk subjects. This will potentially allow
selection of the appropriate high-risk patient population for future studies of
JNJ 56021927 and AAP.
PATIENT-REPORTED OUTCOMES EVALUATIONS
Three PRO instruments, the Functional Assessment of Cancer Therapy-Prostate
(FACT-P), BPI-SF, and EQ-5D-5L will be administered in this study.
Secondary outcome
Overall survival (OS), time to chronic opioid use, time to initiation of
cytotoxic chemotherapy, and time to pain progression.
Background summary
Prostate cancer is the second most frequently diagnosed cancer and the sixth
leading cause of cancer death in males, accounting for 14% (903,500) of the
total new cancer cases and 6% (258,400) of the total cancer deaths in males
worldwide. Treatment aimed at eradicating the
primary tumor, typically with surgery or radiation, is unsuccessful in ~30% of
men, who develop recurrent disease that usually manifests first as a rise in
plasma prostate-specific antigen (PSA) followed by metastasis to distant sites.
Prostate cancers are dependent for their growth and
survival on androgen-mediated signaling. In patients with locally advanced or
metastatic disease, the depletion of androgens through either medical or
surgical castration, decreases androgen receptor (AR) signaling and leads to
tumor regression. Unfortunately, these regressions
in patients with metastatic prostate cancer are universally transient, with a
median duration of disease control between 13 and 22 months and median overall
survival (OS) of 28 to 36 months.
Treatment results with androgen deprivation therapy (ADT; gonadotropin
releasing hormone analogs [GnRHa] or surgical castration with or without
anti-androgens) are generally predictable: a decline in PSA followed by tumor
regression, a period of stability in which the
tumor does not proliferate and PSA remains stable, followed by rising PSA and
regrowth as a castration-resistant disease. Nearly all men with progressive
prostate cancer eventually develop castration-resistant disease. Prostate
cancer progression despite castrate levels of testosterone represents a
transition to a lethal disease stage.
Study objective
This study has been transitioned to CTIS with ID 2023-508606-26-00 check the CTIS register for the current data.
Primary Objective:
The primary objective is to compare the radiographic progression-free survival
(rPFS) of
apalutamide in combination with abiraterone acetate (AA) plus prednisone or
prednisolone
(AAP) and AAP in subjects with chemotherapy-naïve mCRPC.
The major secondary objectives are:
- To characterize the safety profile of apalutamide in combination with AAP
- To characterize the pharmacokinetics (PK) of apalutamide and abiraterone
Study design
This is a randomized, double-blind placebo-controlled, multinational,
multicenter Phase 3 study to determine if subjects with chemotherapy-naïve
mCRPC will benefit from the addition of JNJ-56021927 to AAP compared with AAP.
Subjects will continue receiving gonadotropin releasing hormone analogs (GnRHa)
if not surgically castrated. . Approximately 960 subjects who meet all the
inclusion criteria and none of the exclusion criteria will be randomized in a
1:1 ratio to receive JNJ-56021927 and AAP or matching placebo and AAP. Subjects
will be stratified by the presence or absence of visceral
metastases, Eastern Cooperative Oncology Group (ECOG) Performance Status (PS)
grade of 0 or 1, and region (European Union [EU], North America [United
States/Canada], and Rest of World [ROW]). The study will consist of a Screening
Phase; a Treatment Phase, and a Followup
Phase. The study is anticipated to end approximately 84 months after the first
subject is randomized in to this study.
A treatment cycle is defined as 28 days. Treatment will continue until disease
progression, unacceptable toxicity, death or the sponsor terminates the study.
Subjects must discontinue study drugs with documented unequivocal clinical
progression. If the subject has
radiographic progression, but not unequivocal clinical progression, and
alternate treatment is not
initiated, the subject may continue on study treatment at the Investigator*s
discretion.
After discontinuing study drug, subjects will be contacted every 3 months until
death or termination of the study. In addition to survival follow up, analgesic
use, SSREs, ECOG PS, and subsequent therapy for prostate cancer up to and
including chemotherapy will be
collected. Patient-reported outcomes (PROs) questionnaires will also be
administered every 3 months for up to 12 months after treatment discontinuation
of study treatment.
Subjects will be monitored for safety during the Screening and Treatment Phases
and up to 30 days after the last dose of study drug. Adverse events, including
clinically significant laboratory abnormalities reported as AEs, will be graded
and summarized using National Cancer
Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), Version
4.03. Dose modification guidelines will be provided.
An Independent Data Monitoring Committee (IDMC) will be commissioned for this
study. The committee will perform periodic safety review throughout the study
and review the safety of the first 60 subjects randomized to the study after
treatment for at least 1 cycle. In addition, the IDMC will review the planned
efficacy/futility analysis.
Intervention
DOSAGE AND ADMINISTRATION
All subjects will receive AAP as standard of care (SOC) therapy. Abiraterone
acetate 1,000 mg (4 × 250 mg tablets) will be taken orally once daily.
Abiraterone acetate must be taken on an empty stomach. No food should be
consumed for at least 2 hours before the dose of AA is taken and for at least 1
hour after the dose of AA is taken. Tablets should be swallowed whole with
water. The daily dose of prednisone will be 10 mg (5-mg tablet taken orally
twice daily).
Although not considered study drug, subjects who have not undergone surgical
castration will continue to receive regularly prescribed GnRHa.
JNJ-56021927 240 mg (4 x 60 mg tablets) or Placebo (4 tablets) will be taken
orally once daily. The tablets can be taken with or without food.
Study burden and risks
The possible discomforts, side effects, and risks related to JNJ-56021927
treatment are not all known. Most side effects are not serious. Some may be
serious and may require treatment or additional testing.
Subject will receive the SoC, with or without the investigational drug.
Turnhoutseweg 30
Beerse 2340
BE
Turnhoutseweg 30
Beerse 2340
BE
Listed location countries
Age
Inclusion criteria
1 Subject must be a man age >=18 years of age, inclusive
2 Adenocarcinoma of the prostate
3 Metastatic disease as documented by technetium-99m (99mTc) bone scan or
metastatic lesions by computed tomography (CT) or magnetic resonance imaging
(MRI) scans (visceral or lymph node disease). If lymph node metastasis is the
only evidence of metastasis, it must be greater than or equal to (>=) 2
centimeter (cm) in the longest diameter
4 Castration-resistant prostate cancer demonstrated during continuous androgen
deprivation therapy (ADT), defined as 3 rises of PSA, at least 1 week apart
with the last androgen deprivation therapy (PSA) >= 2 nanogram per
milliliters (ng/mL)
5 Participants who received a first generation anti-androgen (eg, bicalutamide,
flutamide, nilutamide) must have at least a 6-week washout prior to
randomization and must show continuing disease (PSA) progression (an increase
in PSA) after the washout period
6 Prostate cancer progression documented by prostate-specific antigen
(PSA)according to the Prostate Cancer Clinical Trials Working Group
(PCWG2)radiographic progression of soft tissues according to modified Response
Evaluation Criteria in Solid Tumors, version 1.1 (RECIST) modified based on
PCWG2, or radiographic progression of bone according to PCWG2.
Exclusion criteria
1 Small cell or neuroendocrine carcinoma of the prostate
2 Known brain metastases
3 Prior chemotherapy for prostate cancer, except if administered in the
adjuvant/neoadjuvant setting
4 Previously treated with ketoconazole for prostate cancer for greater than 7
days
5 Therapies that must be discontinued or substituted at least 4 weeks prior to
randomization include the following:
a) Medications known to lower the seizure threshold, b) Herbal and nonherbal
products that may decrease PSA levels (example [eg], saw palmetto, pomegranate)
or c) Any investigational agent
6 At screening need for parenteral or oral opioid analgesics (eg, codeine,
dextropropoxyphene)
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 |
|---|---|
| EU-CTR | CTIS2023-508606-26-00 |
| EudraCT | EUCTR2014-001718-25-NL |
| ClinicalTrials.gov | NCT02257736 |
| CCMO | NL51676.056.14 |