An Efficacy and Safety Study of Erdafitinib (JNJ-42756493) in Participants With Urothelial Cancer (NCT02365597) — USA Trial Details

Condition(s) studied

Urothelial Cancer

Investigational drug(s) / intervention(s)

ErdafitinibMidazolamMetformin

Erdafitinib: 8 mg orally once daily for 28 days on a 28 day cycle.

Midazolam: Participants who enrolled in DDI substudy will receive pretreatment with single dose of midazolam on Day -2 and single dose of midazolam on Day 13.

Metformin: Participants who enrolled in DDI substudy will receive pretreatment with single dose of metformin on Day -1 and single dose of metformin on Day 14.

Study summary

The purpose of this study is to evaluate the objective response rate (complete response \[CR\]+ partial response \[PR\]) of the selected dose regimen in participants with metastatic or surgically unresectable urothelial cancers that harbor specific FGFR genomic alterations.

Eligibility

Sex

ALL

Min age

18 Years

Max age

—

Healthy volunteers

No

Inclusion Criteria: * Must have histologic demonstration of metastatic or surgically unresectable urothelial cancer. Minor components of variant histology such as glandular or squamous differentiation, or evolution to more aggressive phenotypes such as sarcomatoid or micropapillary change are acceptable * Must have measurable disease according to the Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1) at baseline * Must have an Eastern Cooperative Oncology Group (ECOG) performance status score 0, 1, or 2 * Must have adequate bone marrow, liver, and renal function as described in protocol * Negative pregnancy test (urine or serum beta human chorionic gonadotropin \[b-hCG\]) at Screening for women of child bearing potential who are sexually active * Must have shown disease progression according to RECIST, version 1.1, following prior chemotherapy for metastatic or surgically unresectable urothelial cancer. Participants who received neoadjuvant or adjuvant chemotherapy and showed disease recurrence or progression according to RECIST, version 1.1, within 12 months of the last dose are considered to have received chemotherapy in the metastatic setting. These participants will be referred to as chemo-refractory participants. (Participants who have shown disease progression according to RECIST, version 1.1 following prior treatment with anti-Programmed death-ligand 1 (anti PDL1/PD1) antibodies are also eligible) For DDI substudy * Disease progression following prior chemotherapy for metastatic or surgically unresectable urothelial cancer. Participants who received neoadjuvant or adjuvant chemotherapy and showed disease recurrence or progression within 12 months of the last dose are considered to have received chemotherapy in the metastatic setting Exclusion Criteria: * Received chemotherapy, targeted therapies, definitive radiotherapy, or treatment with an investigational anticancer agent within 2 weeks (in the case of nitrosoureas and mitomycin C, within 6 weeks; in the case of immunotherapy, within 4 weeks) before the first administration of study drug. Localized palliative radiation therapy (but should not include radiation to target lesions) and ongoing bisphosphonates and denosumab, are permitted * Has persistent phosphate level greater than upper limit of normal (ULN) during screening (within 14 days of treatment and prior to Cycle 1 Day 1) and despite medical management * Has a history of or current uncontrolled cardiovascular disease * Females who are pregnant, breast-feeding, or planning to become pregnant within 3 months after the last dose of study drug and males ho plan to father a child while enrolled in this study or within 5 months after the last dose of study drug * Has not recovered from reversible toxicity of prior anticancer therapy (except toxicities which are not clinically significant such as alopecia, skin discoloration, or Grade 1 neuropathy)

Primary outcome measure(s)

Main Study: Percentage of Participants With Best (Overall) Objective Response — From Cycle 1 Day 1 up to 6 years 2 months
Percentage of participants with best (overall) objective response were reported. Best objective response is defined as the best (overall) objective response a participants achieved during the study in the order of complete response (CR), partial response (PR), stable disease (SD), progressive disease (PD), where CR and PR were confirmed as per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. As per RECIST version 1.1, CR was defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must had reduction in the short axis to less than (\<) 10 millimeters (mm). PR was defined as at least a 30 percent (%) decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Responders are participants with BOR of CR or PR.
Drug-Drug Interaction (DDI) Substudy: Maximum Observed Plasma Concentration (Cmax) of Midazolam Alone or in Combination With Erdafitinib — Cycle 1 Day -2 (predose) up to Day 13 post dose
Cmax is the maximum observed plasma concentration of midazolam alone or in combination with erdafitinib.
Drug-Drug Interaction (DDI) Substudy: Maximum Observed Plasma Concentration (Cmax) of 1-OH-Midazolam (Midazolam Metabolite) Alone or in Combination With Erdafitinib — Cycle 1 Day -2 (predose) up to Day 13 post dose (each cycle length=28 days)
Cmax is the maximum observed plasma concentration of 1-OH-Midazolam (midazolam metabolite) alone or in combination with erdafitinib.
Drug-Drug Interaction (DDI) Substudy: Maximum Observed Plasma Concentration (Cmax) of Metformin Alone or in Combination With Erdafitinib — Cycle 1 Day -1 (predose) up to Day 14 post dose (each cycle length=28 days)
Cmax is the maximum observed plasma concentration of metformin alone or in combination with erdafitinib
Drug-Drug Interaction (DDI) Substudy: Time to Reach the Maximum Observed Plasma Concentration (Tmax) of Midazolam Alone or in Combination With Erdafitinib — Cycle 1 Day -2 (predose) up to Day 13 post dose (each cycle length=28 days)
Tmax is the time to reach the maximum observed plasma concentration of midazolam alone or in combination with erdafitinib.
Drug-Drug Interaction (DDI) Substudy: Time to Reach the Maximum Observed Plasma Concentration (Tmax) of 1-OH-Midazolam (Midazolam Metabolite) Alone or in Combination With Erdafitinib — Cycle 1 Day -2 (predose) up to Day 13 post dose (each cycle length=28 days)
Tmax is the time to reach the maximum observed plasma concentration of 1-OH-Midazolam alone or in combination with erdafitinib.
Drug-Drug Interaction (DDI) Substudy: Time to Reach the Maximum Observed Plasma Concentration (Tmax) of Metformin Alone or in Combination With Erdafitinib — Cycle 1 Day -1 (predose) up to Day 14 post dose (each cycle length=28 days)
Tmax is the time to reach maximum observed plasma concentration of metformin alone or in combination with erdafitinib
Drug-Drug Interaction (DDI) Substudy: Area Under the Plasma Concentration Versus Time Curve From Time 0 to the Time of the Last Measurable Concentration (AUC[0-last]) of Midazolam Alone or in Combination With Erdafitinib — Cycle 1 Day -2 (predose) up to Day 13 post dose (each cycle length=28 days)
AUC(0-last) is the area under the plasma concentration versus time curve from time 0 to the time of the last measurable concentration of midazolam alone or in combination with erdafitinib.
Drug-Drug Interaction (DDI) Substudy: Area Under the Plasma Concentration Versus Time Curve From Time 0 to the Time of the Last Measurable Concentration (AUC[0-last]) of 1-OH-Midazolam (Midazolam Metabolite) Alone or in Combination With Erdafitinib — Cycle 1 Day -2 (predose) up to Day 13 post dose (each cycle length=28 days)
AUC(0-last) is the area under the plasma concentration versus time curve from time 0 to the time of the last measurable concentration of 1-OH-Midazolam alone or in combination with erdafitinib.
Drug-Drug Interaction (DDI) Substudy: Area Under the Plasma Concentration Versus Time Curve From Time 0 to the Time of the Last Measurable Concentration (AUC[0-last]) of Metformin Alone or in Combination With Erdafitinib — Cycle 1 Day -1 (predose) up to Day 14 post dose (each cycle length=28 days)
AUC(0-last) is the area under the plasma concentration versus time curve from time 0 to the time of the last measurable concentration of metformin alone or in combination with erdafitinib.
Drug-Drug Interaction (DDI) Substudy: Area Under the Plasma Concentration Versus Time Curve From Time 0 to the Infinite Time (AUC[0-Infinity]) of Midazolam Alone or in Combination With Erdafitinib — Cycle 1 Day -2 (predose) up to Day 13 post dose (each cycle length=28 days)
AUC(0-Infinity) is the area under the plasma concentration versus time curve from time 0 to the infinite time of midazolam alone or in combination with erdafitinib.
Drug-Drug Interaction (DDI) Substudy: Area Under the Plasma Concentration Versus Time Curve From Time 0 to the Infinite Time (AUC[0-Infinity]) of 1-OH-Midazolam (Midazolam Metabolite) Alone or in Combination With Erdafitinib — Cycle 1 Day -2 (predose) up to Day 13 post dose (each cycle length=28 days)
AUC(0-Infinity) is the area under the plasma concentration versus time curve from time 0 to the infinite time of 1-OH-Midazolam alone or in combination with erdafitinib.
Drug-Drug Interaction (DDI) Substudy: Area Under the Plasma Concentration Versus Time Curve From Time 0 to the Infinite Time (AUC[0-Infinity]) of Metformin Alone or in Combination With Erdafitinib — Cycle 1 Day -1 (predose) up to Day 14 post dose (each cycle length=28 days)
AUC(0-Infinity) is the area under the plasma concentration versus time curve from time 0 to the infinite time of metformin alone or in combination with erdafitinib

Trial sites (105)

Facility	City	Region
—	Sedona	Arizona
—	Los Angeles	California
—	Orange	California
—	Sacramento	California
—	Stanford	California
—	Aurora	Colorado
—	Washington D.C.	District of Columbia
—	Chicago	Illinois
—	Iowa City	Iowa
—	Louisville	Kentucky
—	Minneapolis	Minnesota
—	Omaha	Nebraska
—	Las Vegas	Nevada
—	New York	New York
—	Charlotte	North Carolina
—	Medford	Oregon
—	Tualatin	Oregon
—	Hershey	Pennsylvania
—	Pittsburgh	Pennsylvania
—	Myrtle Beach	South Carolina
—	Nashville	Tennessee
—	Dallas	Texas
—	Denton	Texas
—	Houston	Texas
—	Hampton	Virginia
—	Graz	Austria
—	Linz	Austria
—	Vienna	Austria
—	Aalst	Belgium
—	Brussels	Belgium
—	Charleroi	Belgium
—	Ghent	Belgium
—	Wilrijk	Belgium
—	Angers	France
—	Bordeaux	France
—	Caen Cédex 05	France
—	Dijon	France
—	Lyon	France
—	Nice	France
—	Nîmes	France

+ 65 more sites — see the full list on the official registry below.

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