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

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional

Official Title: A Phase 1 Study of Androgen Receptor (AR) Antagonist JNJ-56021927 in Subjects With Metastatic Castration-Resistant Prostate Cancer

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 Summary: 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.
Sponsor: Janssen Pharmaceutical K.K.

Current Primary Outcome: Number of Participants With Dose Limiting Toxicity [ Time Frame: Week 1 up to Day 28 of Cycle 1 ]

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.


Original Primary Outcome: Number of Participants With Dose Limiting Toxicity [ Time Frame: up to Day 28 of Cycle 1 ]

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.


Current Secondary Outcome:

  • Maximum Observed Plasma Concentration (C[max]) [ Time Frame: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24, 48, 72 and 96 hours post administration of study drug ]
    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]) [ Time Frame: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24, 48, 72 and 96 hours post administration of study drug ]
    The T[max] is time to reach the observed maximum plasma concentration.
  • Elimination Half-life (t1/2[lambda]) [ Time Frame: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24, 48, 72 and 96 hours post administration of study drug ]
    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 [ Time Frame: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24, 48, 72 and 96 hours post administration of study drug ]
    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]) [ Time Frame: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24, 48, 72 and 96 hours post administration of study drug ]
    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]) [ Time Frame: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24, 48, 72 and 96 hours post administration of study drug ]
    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) [ Time Frame: Baseline, Day 1 of each cycle (28 days) until disease progression and up to 28 days after the last dose study drug ]
    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]) [ Time Frame: Pre- dose on Day 1 of Cycle 2 up to Cycle 13 ]
    Trough plasma concentration (C[trough]) just before dosing will be assessed.
  • Observed Accumulation Index (A[cc] Index) [ Time Frame: 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 ]
    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) [ Time Frame: 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 ]
    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) [ Time Frame: 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 ]
    Percent Peak to Trough Fluctuation (PTF) will be calculated as 100 multiplied by {C[max]/C[min]}.


Original Secondary Outcome:

  • Maximum Observed Plasma Concentration (C[max]) [ Time Frame: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24, 48, 72 and 96 hours post administration of study drug ]
    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]) [ Time Frame: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24, 48, 72 and 96 hours post administration of study drug ]
    The T[max] is time to reach the observed maximum plasma concentration.
  • Elimination Half-life (t1/2[lambda]) [ Time Frame: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24, 48, 72 and 96 hours post administration of study drug ]
    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 [ Time Frame: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24, 48, 72 and 96 hours post administration of study drug ]
    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]) [ Time Frame: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24, 48, 72 and 96 hours post administration of study drug ]
    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]) [ Time Frame: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24, 48, 72 and 96 hours post administration of study drug ]
    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) [ Time Frame: Baseline, Day 1 of each cycle (28 days) until disease progression and up to 28 days after the last dose study drug ]
    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 dealyed 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]) [ Time Frame: Pre- dose on Day 1 of Cycle 2 up to Cycle 13 ]
    Trough plasma concentration (C[trough]) just before dosing will be assessed.
  • Observed Accumulation Index (A[cc] Index) [ Time Frame: 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 ]
    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) [ Time Frame: 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 ]
    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) [ Time Frame: 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 ]
    Percent Peak to Trough Fluctuation (PTF) will be calculated as 100 multiplied by {C[max]/C[min]}.


Information By: Janssen Pharmaceutical K.K.

Dates:
Date Received: June 11, 2014
Date Started: June 27, 2014
Date Completion: September 17, 2018
Last Updated: April 13, 2017
Last Verified: April 2017