A Study of Erdafitinib in Participants With Metastatic or Locally Advanced Urothelial Cancer
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| ClinicalTrials.gov Identifier: NCT03473743 |
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Recruitment Status :
Active, not recruiting
First Posted : March 22, 2018
Last Update Posted : December 29, 2022
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Sponsor:
Janssen Research & Development, LLC
Information provided by (Responsible Party):
Janssen Research & Development, LLC
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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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Urothelial Carcinoma | Drug: Erdafitinib Drug: Cetrelimab Drug: Cisplatin Drug: Carboplatin | Phase 1 Phase 2 |
Expanded Access : An investigational treatment associated with this study has been approved for sale to the public. More info ...
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 : | Interventional (Clinical Trial) |
| Actual Enrollment : | 125 participants |
| Allocation: | Randomized |
| Intervention Model: | Sequential Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | 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 |
| Actual Study Start Date : | April 5, 2018 |
| Estimated Primary Completion Date : | June 16, 2023 |
| Estimated Study Completion Date : | June 16, 2023 |
Resource links provided by the National Library of Medicine
Drug Information available for:
Erdafitinib
| Arm | Intervention/treatment |
|---|---|
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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.
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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. |
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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).
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Drug: Erdafitinib
Participants will receive erdafitinib orally.
Other Name: JNJ-42756493 Drug: Cetrelimab Participants will receive cetrelimab by intravenous infusion.
Other Name: JNJ-63723283 |
Primary Outcome Measures :
- 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.
Secondary Outcome Measures :
- 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.
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
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
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03473743
Locations
Show 127 study locations
Sponsors and Collaborators
Janssen Research & Development, LLC
Investigators
| Study Director: | Janssen Research & Development, LLC Clinical Trial | Janssen Research & Development, LLC |
| Responsible Party: | Janssen Research & Development, LLC |
| ClinicalTrials.gov Identifier: | NCT03473743 |
| Other Study ID Numbers: |
CR108445 2017-001980-19 ( EudraCT Number ) 42756493BLC2002 ( Other Identifier: Janssen Research & Development, LLC ) |
| First Posted: | March 22, 2018 Key Record Dates |
| Last Update Posted: | December 29, 2022 |
| Last Verified: | December 2022 |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Additional relevant MeSH terms:
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Carcinoma, Transitional Cell Carcinoma Neoplasms, Glandular and Epithelial Neoplasms by Histologic Type |
Neoplasms Cisplatin Carboplatin Antineoplastic Agents |