Clinical trial NCT02162836: A Safety Study of JNJ-56021927 in Participants With Metastatic Castration-Resistant Prostate Cancer
Official title: A Phase 1 Study of Androgen Receptor (AR) Antagonist JNJ-56021927 in Subjects With Metastatic Castration-Resistant Prostate Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Prostatic Neoplasms, Castration-Resistant
Keywords: Prostatic Neoplasms, Castration-Resistant
Metastatic Castration-Resistant Prostate Cancer
Prostate Cancer
Androgen Receptor
JNJ-56021927
Lead sponsor: Janssen Pharmaceutical K.K.
Sponsor class: INDUSTRY
First posted: 2014-06-13
Enrollment: 6
Sex: MALE
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the safety and tolerability of JNJ-56021927 in Japanese participants with metastatic castration-resistant prostate cancer (mCRPC- prostate cancer that is resistant to medical \[for example. hormonal\] or surgical treatments).

Detailed description: This is a Phase 1, multicenter, open-label (participants will know the identity of study drug received) study in participants with Metastatic Castration-Resistant Prostate Cancer (mCRPC). The study consists of 4 parts: Screening (28 days before study commences on Day 1), pharmacokinetic week (PK), Continuous daily dosing, Extension and Safety follow-up period. In PK week participants will receive a single oral capsule of JNJ-56021927 at a dose of 240 milligram (mg) on Day 1 and will be monitored for 1 week. After Week 1, in continuous daily dosing period, participants will receive continuous daily therapy at the same dose for 4 weeks (Cycle 1). After Cycle 1 participants, who will not meet the criteria for discontinuation listed such as progressive disease (PD) or unacceptable toxicity, will continue in safety follow-up period and will receive continuous daily therapy at the same dose up to cycle 13. Primarily dose limiting toxicity (DLT) will be evaluated. Participants' safety will be monitored throughout.

Eligibility criteria: Inclusion Criteria:

* Histologically or cytologically confirmed adenocarcinoma of the prostate without neuroendocrine differentiation or small cell features, with metastatic disease
* Castration-resistant prostate cancer (CRPC) demonstrated during continuous androgen deprivation therapy (ADT)/post orchiectomy
* Maintain castrate levels of testosterone (less than \[\<\] 50 nanogram per deciliter (ng/dL) \[1.72 nanomol per liter {nmol/L}\]) within 4 weeks before enrollment
* Prostate-specific antigen (PSA) evidence for progressive prostate cancer consists of a PSA level of at least greater than or equal to (\>=) 2 nanogram per milliliter (ng/mL) within 2 weeks before enrollment which has risen on at least 2 successive occasions, at least 1 week apart. If the confirmatory PSA value is less than the last PSA value, then an additional test for rising PSA will be required to document progression
* Participants who received a first generation anti-androgen \[for example, bicalutamide, flutamide, nilutamide (not approved in Japan)\] as part of an initial combined androgen blockade therapy or as second-line hormonal therapy must show continuing disease progression off the anti-androgen for at least 4 weeks prior to the first dose of study drug

Exclusion Criteria:

* History of, or current metastases in the brain or untreated spinal cord compression
* Participants with progressive epidural disease
* Participants has a history of another malignancy within 5 years before screening
* Prior treatment with second generation anti-androgens ( for example, enzalutamide) or Cytochrome P450 17 (CYP 17) inhibitors \[for example, abiraterone acetate, orteronel, galeterone, systemic ketoconazole (not approved in Japan, respectively)\]
* Participants had used radiopharmaceutical agents (for example, Strontium-89) or investigational immunotherapy (for example, sipuleucel-T) within 12 weeks before the first dose of study drug

Primary outcomes:
measure: Number of Participants With Dose Limiting Toxicity
timeFrame: Week 1 up to Day 28 of Cycle 1
Secondary outcomes:
measure: Maximum Observed Plasma Concentration (C[max])
timeFrame: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24, 48, 72 and 96 hours post administration of study drug
measure: Time to Reach the Maximum Plasma Concentration (T[max])
timeFrame: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24, 48, 72 and 96 hours post administration of study drug
measure: Elimination Half-life (t1/2[lambda])
timeFrame: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24, 48, 72 and 96 hours post administration of study drug
measure: Area Under the Plasma Concentration-Time Curve From Time Zero to 24 Hours
timeFrame: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24, 48, 72 and 96 hours post administration of study drug
measure: Area Under the Plasma Concentration-Time Curve From Time Zero to Infinite Time (AUC [0-last])
timeFrame: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24, 48, 72 and 96 hours post administration of study drug
measure: Area Under the Plasma Concentration-Time Curve From Time Zero to Infinite Time (AUC [0-infinity])
timeFrame: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24, 48, 72 and 96 hours post administration of study drug
measure: Change in Prostate-specific Antigen (PSA)
timeFrame: Baseline, Day 1 of each cycle (28 days) until disease progression and up to 28 days after the last dose study drug
measure: Trough Plasma Concentration (C[trough])
timeFrame: Pre- dose on Day 1 of Cycle 2 up to Cycle 13
measure: Observed Accumulation Index (A[cc] Index)
timeFrame: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24, 48, 72 and 96 hours post administration of study drug in Cycle 1
measure: Effective Half-life (EHL)
timeFrame: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24, 48, 72 and 96 hours post administration of study drug in Cycle 1
measure: Percent Peak to Trough Fluctuation (PTF)
timeFrame: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24, 48, 72 and 96 hours post administration of study drug in Cycle 1
Other outcomes:
Locations:
city: Fukuoka
country: Japan
city: Gifu
country: Japan
city: Matsuyama
country: Japan
city: Yokohama
country: Japan
Study officials:
affiliation: Janssen Pharmaceutical K.K.
name: Janssen Pharmaceutical K.K., Japan Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Tsuchiya T, Imanaka K, Iwaki Y, Oyama R, Hashine K, Yamaguchi A, Uemura H. An open-label, phase 1 study of androgen receptor antagonist, apalutamide in Japanese patients with metastatic castration-resistant prostate cancer. Int J Clin Oncol. 2019 Dec;24(12):1596-1604. doi: 10.1007/s10147-019-01526-7. Epub 2019 Aug 24.
citation: Uemura H, Koroki Y, Iwaki Y, Imanaka K, Kambara T, Lopez-Gitlitz A, Smith A, Uemura H. Skin rash following Administration of Apalutamide in Japanese patients with Advanced Prostate Cancer: an integrated analysis of the phase 3 SPARTAN and TITAN studies and a phase 1 open-label study. BMC Urol. 2020 Sep 2;20(1):139. doi: 10.1186/s12894-020-00689-0.