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A Study of Erdafitinib in Participants With Metastatic or Locally Advanced Urothelial Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03473743
Recruitment Status : Recruiting
First Posted : March 22, 2018
Last Update Posted : January 3, 2022
Sponsor:
Information provided by (Responsible Party):
Janssen Research & Development, LLC

Tracking Information
First Submitted Date  ICMJE March 14, 2018
First Posted Date  ICMJE March 22, 2018
Last Update Posted Date January 3, 2022
Actual Study Start Date  ICMJE April 5, 2018
Estimated Primary Completion Date March 17, 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 24, 2020)
  • Phase 1b: Percentage of Participants with Dose-Limiting Toxicity (DLT) [ Time Frame: Up to 8 weeks ]
    The Dose Limiting Toxicities (DLTs) are based on drug related adverse events and defined as any of the following events: hematological / non hematological toxicity of Grade 3 or higher.
  • Phase 2: Overall Response Rate (ORR) (Partial Response [PR] or Better) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 by Investigator Assessment [ Time Frame: Up to 2 years ]
    ORR is defined as the percentage of participants with PR or complete response (CR) as defined by RECIST 1.1, as assessed by the investigator.
  • Phase 2: Number of Participants with Adverse Event (AEs) [ Time Frame: Up to 2 years ]
    An AE is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.
Original Primary Outcome Measures  ICMJE
 (submitted: March 21, 2018)
  • Phase 1b: Percentage of Participants with Dose-Limiting Toxicity (DLT) [ Time Frame: Approximately up to 8 weeks ]
    The Dose Limiting Toxicities (DLTs) are based on drug related adverse events and defined as any of the following events: hematological / non hematological toxicity of Grade 3 or higher.
  • Phase 1b: Number of Participants with Adverse Events (AEs) [ Time Frame: Approximately up to 2 years ]
    An AE is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.
  • Phase 2: Overall Response Rate (ORR) (Partial Response [PR] or Better) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 [ Time Frame: Approximately up to 2 years ]
    ORR is defined as the percentage of participants with PR or complete response (CR) as defined by RECIST 1.1, as assessed by the investigator.
  • Phase 2: Number of Participants with AEs [ Time Frame: Approximately up to 2 years ]
    An AE is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 27, 2021)
  • Phase 1b and Phase 2: Plasma Concentration of Erdafitinib [ Time Frame: Cycle(C)1 Day(D)1 up to C3D1 (each cycle of 28 days) ]
    Plasma concentrations will be reported for erdafitinib.
  • Phase 1b and Phase 2: Serum Concentration of Cetrelimab [ Time Frame: Up to Follow-up (approximately up to 2 years) ]
    Serum concentrations will be reported for cetrelimab.
  • Phase 1b: Plasma Concentration of Platinum (Cisplatin and Carboplatin) Chemotherapy [ Time Frame: C1D1 up to C4D1 (each cycle of 21 days) ]
    Plasma concentrations will be reported for platinum (cisplatin and carboplatin) chemotherapy.
  • Phase 1b and Phase 2: Number of Participants with Anti-Cetrelimab Antibodies [ Time Frame: Up to Follow-up (approximately up to 2 years) ]
    Number of participants with anti-cetrelimab antibodies will be reported.
  • Phase 2: Number of Participants with Serious Adverse Events (SAEs) [ Time Frame: Up to 2 years ]
    An SAE is any AE that results in: death, persistent or significant disability/incapacity, requires inpatient hospitalization or prolongation of existing hospitalization, is life-threatening experience, is a congenital anomaly/birth defect and may jeopardize participant and/or may require medical or surgical intervention to prevent one of the outcomes listed above.
  • Phase 2: Number of Participants with Abnormal Laboratory Values [ Time Frame: Up to 2 years ]
    Number of participants with abnormal laboratory values will be reported.
  • Phase 2: Duration of Response (DoR) [ Time Frame: Up to 2 years ]
    DoR is defined as the time from the date of initial documentation of a response (CR or PR) to the date of first documented evidence of progressive disease (or relapse for participants who experience CR during the study) or death.
  • Phase 2: Time to Response (TTR) [ Time Frame: Up to 2 years ]
    TTR is defined as the time from the date of randomization to the date of initial documentation of a response (CR or PR).
  • Phase 2: Progression-Free Survival (PFS) [ Time Frame: Up to 2 years ]
    PFS is defined as the duration from the date of randomization until the date of first documented evidence of progressive disease (or relapse for participants who experience CR during the study) or death, whichever comes first.
  • Phase 2: Overall Survival (OS) [ Time Frame: Up to 2 years ]
    OS is defined as the time from the date of randomization to the date of the participant's death.
Original Secondary Outcome Measures  ICMJE
 (submitted: March 21, 2018)
  • Phase 1b and Phase 2: Plasma Concentration of Erdafitinib [ Time Frame: Cycle(C)1 Day(D)1 up to C3D1 (each cycle of 28 days) ]
    Plasma concentrations will be reported for erdafitinib.
  • Phase 1b and Phase 2: Serum Concentration of JNJ-63723283 [ Time Frame: Up to Follow-up (approximately up to 2 years) ]
    Serum concentrations will be reported for JNJ-63723283.
  • Phase 1b and Phase 2: Number of Participants with Anti-JNJ-63723283 Antibodies [ Time Frame: Up to Follow-up (approximately up to 2 years) ]
    Number of participants with anti-JNJ-63723283 antibodies will be reported.
  • Phase 2: Number of Participants with Serious Adverse Events (SAEs) [ Time Frame: Approximately up to 2 years ]
    An SAE is any AE that results in: death, persistent or significant disability/incapacity, requires inpatient hospitalization or prolongation of existing hospitalization, is life-threatening experience, is a congenital anomaly/birth defect and may jeopardize participant and/or may require medical or surgical intervention to prevent one of the outcomes listed above.
  • Phase 2: Number of Participants with Abnormal Laboratory Values [ Time Frame: Approximately up to 2 years ]
    Number of participants with abnormal laboratory values will be reported.
  • Phase 2: Duration of Response (DoR) [ Time Frame: Approximately up to 2 years ]
    DoR is defined as the time from the date of initial documentation of a response (CR or PR) to the date of first documented evidence of progressive disease (or relapse for participants who experience CR during the study) or death.
  • Phase 2: Time to Response (TTR) [ Time Frame: Approximately up to 2 years ]
    TTR is defined as the time from the date of randomization to the date of initial documentation of a response (CR or PR).
  • Phase 2: Progression-Free Survival (PFS) [ Time Frame: Approximately up to 2 years ]
    PFS is defined as the duration from the date of randomization until the date of first documented evidence of progressive disease (or relapse for participants who experience CR during the study) or death, whichever comes first.
  • Phase 2: Overall Survival (OS) [ Time Frame: Approximately up to 2 years ]
    OS is defined as the time from the date of randomization to the date of the participant's death.
  • Phase 2: Overall Response Rate (ORR) per Immune-Related RECIST (iRECIST) Criteria [ Time Frame: Approximately up to 2 years ]
    ORR is defined as the percentage of participants who achieve CR or PR, as defined by iRECIST, as assessed by the investigator.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of Erdafitinib in Participants With Metastatic or Locally Advanced Urothelial Cancer
Official Title  ICMJE A Phase 1b-2 Study to Evaluate Safety, Efficacy, Pharmacokinetics, and Pharmacodynamics of Various Regimens of Erdafitinib in Subjects With Metastatic or Locally Advanced Urothelial Cancer
Brief Summary The purpose of this study is to: (a) characterize the safety and tolerability of and to identify the recommended Phase 2 dose (RP2D) and schedule for erdafitinib in combination with cetrelimab, and for erdafitinib in combination with cetrelimab and platinum (cisplatin and carboplatin) chemotherapy and; (b) to evaluate the safety and clinical activity of erdafitinib alone and in combination with cetrelimab in cisplatin-ineligible participants with metastatic or locally advanced urothelial cancer (UC) with select fibroblast growth factor receptor (FGFR) gene alterations and no prior systemic therapy for metastatic disease.
Detailed Description This open-label (all people know identity of intervention) and multicenter (when more than one hospital or medical school team work on a medical research study) study to establish the recommended phase 2 dose (RP2D) for erdafitinib and cetrelimab and/or platinum (cisplatin or carboplatin) chemotherapy, and to evaluate the safety of erdafitinib in combination with cetrelimab and platinum chemotherapy in Phase 1b and to evaluate the safety and efficacy of the RP2D of erdafitinib plus cetrelimab versus erdafitinib in Phase 2 in participants with advanced urothelial cancer with select fibroblast growth factor receptor (FGFR) gene alterations. Participants enrolled in Phase 1b erdafitinib + cetrelimab cohort may have received any number of lines of prior therapy, and participants enrolled in Phase 1b erdafitinib + cetrelimab + platinum chemotherapy cohort will have had no prior systemic therapy for metastatic disease and participants enrolled in Phase 2 will have had no prior systemic therapy for metastatic disease and will be cis-ineligible. Part 1 (Phase 1b: Dose Escalation) will identify safety and RP2Ds of erdafitinib + cetrelimab and erdafitinib + cetrelimab + platinum (cisplatin or carboplatin) chemotherapy, and Part 2 (Phase 2: Dose Expansion) will evaluate erdafitinib monotherapy and the RP2D regimen of the erdafitinib + cetrelimab combination to further characterize safety and clinical activity. The study will be conducted in 3 phases: screening phase, treatment phase, and follow-up phase. Study evaluations include efficacy, pharmacokinetics, pharmacodynamics, immunogenicity, biomarkers, and safety.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Urothelial Carcinoma
Intervention  ICMJE
  • Drug: Erdafitinib
    Participants will receive erdafitinib orally.
    Other Name: JNJ-42756493
  • Drug: Cetrelimab
    Participants will receive cetrelimab by intravenous infusion.
    Other Name: JNJ-63723283
  • Drug: Cisplatin
    Participants will receive cisplatin by intravenous infusion as a part of platinum chemotherapy.
  • Drug: Carboplatin
    Participants will receive carboplatin by intravenous infusion as a part of platinum chemotherapy.
Study Arms  ICMJE
  • Experimental: Phase 1b: Dose Escalation
    Two dosing cohorts (erdafitinib and cetrelimab; and erdafitinib, cetrelimab and cisplatin/carboplatin) are explored in Phase 1b of the study. Participants will receive erdafitinib orally followed by cetrelimab intravenously (IV) and carboplatin/cisplatin IV as a part of platinum chemotherapy. The dose levels will be escalated sequentially based on the decisions of the Study Evaluation Team (SET) until the recommended Phase 2 Dose (RP2D) has been identified.
    Interventions:
    • Drug: Erdafitinib
    • Drug: Cetrelimab
    • Drug: Cisplatin
    • Drug: Carboplatin
  • Experimental: Phase 2: Dose Expansion
    The participants will be randomized in a 1:1 manner to receive either erdafitinib alone (orally) or the identified RP2D of Phase 1b for erdafitinib (orally) in combination with cetrelimab (IV).
    Interventions:
    • Drug: Erdafitinib
    • Drug: Cetrelimab
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: October 7, 2021)
126
Original Estimated Enrollment  ICMJE
 (submitted: March 21, 2018)
102
Estimated Study Completion Date  ICMJE September 30, 2023
Estimated Primary Completion Date March 17, 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Histologic demonstration of transitional cell carcinoma of the urothelium. Variant urothelial carcinoma histologies such as glandular or squamous differentiation, or evolution to more aggressive phenotypes such as sarcomatoid or micropapillary change are acceptable
  • Metastatic or locally advanced urothelial cancer
  • Must have measurable disease by radiological imaging according to the Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1) at baseline
  • Prior systemic therapy for metastatic urothelial cancer: (a) For Phase 1b erdafitinib + cetrelimab cohort: Any number of lines of prior therapy; (b) For Phase 1b erdafitinib + cetrelimab + platinum chemotherapy cohort: No prior systemic therapy for metastatic disease; and renal function for participants must have a creatinine clearance (CrCl) greater than (>) 30 milliliter per minute (mL/min) to receive carboplatin and >60 mL/min to receive cisplatin as calculated by Cockcroft Gault and (c) Phase 2: No prior systemic therapy for metastatic disease and cisplatin-ineligible based on: ECOG PS 0-1 and at least one of the following criteria: Renal function defined as creatinine clearance (CrCl) less than (˂) 60 mL/min as calculated by Cockcroft-Gault; Grade 2 or higher peripheral neuropathy per NCI-CTCAE version 5.0; Grade 2 or higher hearing loss per NCI-CTCAE version 5.0 OR ECOG PS 2
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) grade of: (a) Phase 1b erdafitinib + cetrelimab cohort: ECOG 0-2; (b) Phase 1b erdafitinib + cetrelimab + platinum chemotherapy cohort: ECOG 0-1 for cisplatin and 0-2 for carboplatin (c) Phase 2: ECOG 0-2

Exclusion Criteria:

  • Treatment with any other investigational agent or participation in another clinical study with therapeutic intent within 30 days prior to Cycle 1 Day 1. For Phase 1b, participants who have received the following prior antitumor therapy: received nitrosoureas and mitomycin C within 6 weeks
  • Phase 1b erdafitinib + cetrelimab cohort: Chemotherapy within 3 weeks of Cycle 1 Day 1; Phase 1b erdafitinib + cetrelimab + platinum chemotherapy cohort and Phase 2: Prior neoadjuvant/adjuvant chemotherapy is allowed if the last dose was given >12 months prior to recurrent disease progression and did not result in drug-related toxicity leading to treatment discontinuation
  • Prior anti-programmed death receptor-1 (PD-1), anti-programmed death ligand-1 (PD-L1), or anti-programmed death ligand-2 (PD-L2) therapy. Prior neoadjuvant/adjuvant checkpoint inhibitor therapy is allowed if the last dose was given more than (>)12 months prior to recurrent disease progression and did not result in drug-related toxicity leading to treatment discontinuation. PD-1 for non-muscle invasive bladder cancer is also allowed
  • Active malignancies requiring concurrent therapy other than urothelial cancer
  • Symptomatic central nervous system metastases
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Study Contact 844-434-4210 JNJ.CT@sylogent.com
Listed Location Countries  ICMJE Belarus,   Belgium,   Brazil,   France,   Georgia,   Italy,   Korea, Republic of,   Poland,   Russian Federation,   Spain,   Taiwan,   Turkey,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03473743
Other Study ID Numbers  ICMJE CR108445
2017-001980-19 ( EudraCT Number )
42756493BLC2002 ( Other Identifier: Janssen Research & Development, LLC )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Janssen Research & Development, LLC
Study Sponsor  ICMJE Janssen Research & Development, LLC
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Janssen Research & Development, LLC Clinical Trial Janssen Research & Development, LLC
PRS Account Janssen Research & Development, LLC
Verification Date December 2021

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