A Safety Study of JNJ-56021927 in Participants With Metastatic Castration-Resistant Prostate Cancer

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Primary Purpose

Status

Completed

Phase

Phase 1

Locations

Japan

Study Type

Interventional

Intervention

JNJ-56021927

About this trial

This is an interventional treatment trial for Prostatic Neoplasms, Castration-Resistant focused on measuring Prostatic Neoplasms, Castration-Resistant, Metastatic Castration-Resistant Prostate Cancer, Prostate Cancer, Androgen Receptor, JNJ-56021927

Eligibility Criteria

20 Years - undefined (Adult, Older Adult)MaleDoes not accept healthy volunteers

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

Sites / Locations

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Cohort 1

Arm Description

Participants will receive 8 capsules of JNJ-56021927, 240 milligram (mg) as single oral dose on Day 1. After participants will receive daily JNJ-56021927, 240 mg on Day 1 of Cycle 1 until disease progression, unacceptable toxicity, withdrawal of consent or death, whichever comes first.

Outcomes

Primary Outcome Measures

Number of Participants With Dose Limiting Toxicity

The dose will be considered intolerable if a participants developed either any Grade 3 or 4 non-hematologic toxicity; GI toxicities such as abdominal pain, nausea, vomiting, constipation, and diarrhea, must persist at Grade 3-4 despite maximal medical therapy, Grade 4 neutropenia (that is, ANC less than [<] 500 per microliter [mcL] for five or more consecutive days, Grade 4 thrombocytopenia (<25,000 per mcL) or Grade 3 thrombocytopenia (greater than or equal to [>=] 25,000 - <50,000 per mcL) with a bleeding episode requiring platelet transfusion, any other Grade 4 hematologic toxicity of more than 5 days duration, any grade treatment-related seizure, the other toxicities which do not meet any of the above criteria but which, in the opinion of the Investigator, are equivalent to DLTs.

Secondary Outcome Measures

Maximum Observed Plasma Concentration (C[max])

The C(max) is the maximum plasma concentration which will be observed at the defined time points.

Time to Reach the Maximum Plasma Concentration (T[max])

The T[max] is time to reach the observed maximum plasma concentration.

Elimination Half-life (t1/2[lambda])

Elimination half-life associated with the terminal slope (lambda[z]) of the semi logarithmic drug concentration-time curve, calculated as 0.693/lambda (z).

Area Under the Plasma Concentration-Time Curve From Time Zero to 24 Hours

The AUC (0-24) is the area under the plasma concentration-time curve from time zero to 24 hours.

Area Under the Plasma Concentration-Time Curve From Time Zero to Infinite Time (AUC [0-last])

The AUC (0-last) is the area under the plasma concentration-time curve from time zero time of the last quantifiable concentration C(last), and C(last) is the last observed quantifiable concentration.

Area Under the Plasma Concentration-Time Curve From Time Zero to Infinite Time (AUC [0-infinity])

The AUC (0-infinity) is the area under the plasma concentration-time curve from time zero to infinite time, calculated as the sum of AUC(0-last) and C(last)/lambda(z), wherein AUC(0-last) is area under the plasma concentration-time curve from time zero to last quantifiable time; and C(last) is the last observed quantifiable concentration; and lambda(z) is elimination rate constant.

Change in Prostate-specific Antigen (PSA)

Change in prostate specific antigen will be assessed using the Prostate Cancer Working Group 2 (PCWG2) criteria and Response Criteria in Solid Tumors (RECIST). PSA progression will delayed if decline from baseline: greater than or equal to (>=) 25 percent (%) and >= 2 nanogram per milliliter (ng/mL) above the PSA nadir, which is confirmed by a second value 3 or more weeks later; and no decline from baseline: PSA progression >= 25% and >= 2 ng/mL after 12 weeks.

Trough Plasma Concentration (C[trough])

Trough plasma concentration (C[trough]) just before dosing will be assessed.

Observed Accumulation Index (A[cc] Index)

Observed Accumulation Index (A[cc] Index) will be calculated as AUC[0-24] at steady state divided by AUC[0-24].

Effective Half-life (EHL)

Effective Half-life (EHL) will be calculated as dosing interval minus log 2 divided by log {1-[1/A[cc]Index}.

Percent Peak to Trough Fluctuation (PTF)

Percent Peak to Trough Fluctuation (PTF) will be calculated as 100 multiplied by {C[max]/C[min]}.

Full Information

NCT ID

NCT02162836

First Posted

June 11, 2014

Last Updated

April 24, 2020

Sponsor

Janssen Pharmaceutical K.K.

1. Study Identification

Unique Protocol Identification Number

NCT02162836

Brief Title

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

2. Study Status

Record Verification Date

April 2020

Overall Recruitment Status

Completed

Study Start Date

June 27, 2014 (Actual)

Primary Completion Date

May 27, 2019 (Actual)

Study Completion Date

May 27, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Janssen Pharmaceutical K.K.

4. Oversight

Studies a U.S. FDA-regulated Device Product

No

Data Monitoring Committee

No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Prostatic Neoplasms, Castration-Resistant

Keywords

Prostatic Neoplasms, Castration-Resistant, Metastatic Castration-Resistant Prostate Cancer, Prostate Cancer, Androgen Receptor, JNJ-56021927

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

6 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Cohort 1

Arm Type

Experimental

Arm Description

Participants will receive 8 capsules of JNJ-56021927, 240 milligram (mg) as single oral dose on Day 1. After participants will receive daily JNJ-56021927, 240 mg on Day 1 of Cycle 1 until disease progression, unacceptable toxicity, withdrawal of consent or death, whichever comes first.

Intervention Type

Drug

Intervention Name(s)

JNJ-56021927

Intervention Description

Participants will receive 8 capsules of JNJ-56021927, 240 milligram (mg) as single oral dose on Day 1. After participants will receive daily JNJ-56021927, 240 mg on Day 1 of Cycle 1 until disease progression, unacceptable toxicity, withdrawal of consent or death, whichever comes first.

Primary Outcome Measure Information:

Title

Number of Participants With Dose Limiting Toxicity

Description

The dose will be considered intolerable if a participants developed either any Grade 3 or 4 non-hematologic toxicity; GI toxicities such as abdominal pain, nausea, vomiting, constipation, and diarrhea, must persist at Grade 3-4 despite maximal medical therapy, Grade 4 neutropenia (that is, ANC less than [<] 500 per microliter [mcL] for five or more consecutive days, Grade 4 thrombocytopenia (<25,000 per mcL) or Grade 3 thrombocytopenia (greater than or equal to [>=] 25,000 - <50,000 per mcL) with a bleeding episode requiring platelet transfusion, any other Grade 4 hematologic toxicity of more than 5 days duration, any grade treatment-related seizure, the other toxicities which do not meet any of the above criteria but which, in the opinion of the Investigator, are equivalent to DLTs.

Time Frame

Week 1 up to Day 28 of Cycle 1

Secondary Outcome Measure Information:

Title

Maximum Observed Plasma Concentration (C[max])

Description

The C(max) is the maximum plasma concentration which will be observed at the defined time points.

Time Frame