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

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ClinicalTrials.gov Identifier: NCT02162836
Recruitment Status : Active, not recruiting
First Posted : June 13, 2014
Last Update Posted : June 25, 2018
Sponsor:
Information provided by (Responsible Party):
Janssen Pharmaceutical K.K.

June 11, 2014
June 13, 2014
June 25, 2018
June 27, 2014
May 15, 2020   (Final data collection date for primary outcome measure)
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.
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.
Complete list of historical versions of study NCT02162836 on ClinicalTrials.gov Archive Site
  • 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]}.
  • 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]}.
Not Provided
Not Provided
 
A Safety Study of JNJ-56021927 in Participants With Metastatic Castration-Resistant Prostate Cancer
A Phase 1 Study of Androgen Receptor (AR) Antagonist JNJ-56021927 in Subjects With Metastatic Castration-Resistant Prostate Cancer
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).
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.
Interventional
Phase 1
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Prostatic Neoplasms, Castration-Resistant
Drug: JNJ-56021927
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.
Experimental: Cohort 1
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: Drug: JNJ-56021927
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
6
12
May 15, 2020
May 15, 2020   (Final data collection date for primary outcome measure)

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
Sexes Eligible for Study: Male
20 Years and older   (Adult, Older Adult)
No
Contact information is only displayed when the study is recruiting subjects
Japan
 
 
NCT02162836
CR103653
56021927PCR1008 ( Other Identifier: Janssen Pharmaceutical K.K )
No
Studies a U.S. FDA-regulated Device Product: No
Not Provided
Janssen Pharmaceutical K.K.
Janssen Pharmaceutical K.K.
Not Provided
Study Director: Janssen Pharmaceutical K.K., Japan Clinical Trials Janssen Pharmaceutical K.K.
Janssen Pharmaceutical K.K.
June 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP