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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03390504




Registration number
NCT03390504
Ethics application status
Date submitted
20/12/2017
Date registered
4/01/2018
Date last updated
14/08/2024

Titles & IDs
Public title
A Study of Erdafitinib Compared With Vinflunine or Docetaxel or Pembrolizumab in Participants With Advanced Urothelial Cancer and Selected Fibroblast Growth Factor Receptor (FGFR) Gene Aberrations
Scientific title
A Phase 3 Study of Erdafitinib Compared With Vinflunine or Docetaxel or Pembrolizumab in Subjects With Advanced Urothelial Cancer and Selected FGFR Gene Aberrations
Secondary ID [1] 0 0
2017-002932-18
Secondary ID [2] 0 0
CR108401
Universal Trial Number (UTN)
Trial acronym
THOR
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Urothelial Cancer 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional(has expanded access)
Description of intervention(s) / exposure
Treatment: Drugs - Erdafitinib
Treatment: Drugs - Vinflunine
Treatment: Drugs - Docetaxel
Treatment: Drugs - Pembrolizumab
Treatment: Devices - Fibroblast Growth Factor Receptor inhibitor Clinical Trial Assay (FGFRi CTA)

Experimental: Cohort 1 (Arm 1A): Erdafitinib - Participants will be screened based on Fibroblast Growth Factor Receptor Inhibitor Clinical Trial Assay (FGFRi CTA) to determine molecular eligibility and participants who meet molecular eligibility criteria will be eligible for full study screening. Participants enrolled in the study (treated with prior anti-programmed cell death protein PD-\[L\] 1 agent) will swallow erdafitinib tablets orally at a starting dose of 8 milligram (mg), once daily for 21 days in a 21-day cycle until disease progression, intolerable toxicity, withdrawal of consent or decision by the investigator to discontinue treatment. Dose adjustment are based on phosphate level and observed toxicity (adverse events \[AEs\]). Participants who enter in Long-term extension (LTE) phase will continue to receive the erdafitinib tablet as per investigator's decision.

Experimental: Cohort 1 (Arm 1B): Vinflunine or Docetaxel - Participants will be screened based on FGFRi CTA to determine molecular eligibility and participants who meet molecular eligibility criteria will be eligible for full study screening. Participants enrolled in the study (treated with prior anti-PD-\[L\] 1 agent) will receive vinflunine 320 milligram per meter square (mg/m\^2) as a 20-minute intravenous infusion once every 3 weeks or docetaxel 75 mg/m\^2 as a 1 hour intravenous infusion every 3 weeks. Treatment with either agent (choice of investigator) will be administered until disease progression, intolerable toxicity, withdrawal of consent or decision by the investigator to discontinue treatment. Dose adjustments are based on observed toxicities. Participants who enter in LTE phase will continue to receive Vinflunine or Docetaxel until the participant can commercially receive chemotherapy within the local healthcare system.

Experimental: Cohort 2 (Arm 2A): Erdafitinib - Participants will be screened based on FGFRi CTA to determine molecular eligibility and participants who meet molecular eligibility criteria will be eligible for full study screening. Participants enrolled in the study (no prior treatment with anti-PD-\[L\] 1 agent) will swallow erdafitinib tablets orally at a starting dose of 8 mg, once daily for 21 days in a 21-day cycle until disease progression, intolerable toxicity, withdrawal of consent or decision by the investigator to discontinue treatment. Dose adjustments are based on phosphate level and observed toxicity (AEs). Participants who enter in LTE phase will continue to receive the erdafitinib tablet as per investigator's decision.

Experimental: Cohort 2 (Arm 2B): Pembrolizumab - Participants will be screened based on FGFRi CTA to determine molecular eligibility and participants who meet molecular eligibility criteria will be eligible for full study screening. Participants enrolled in the study (no prior treatment with anti-PD-\[L\] 1 agent) will receive pembrolizumab 200 mg as a 30-minute intravenous infusion once every 3 weeks, until disease progression, intolerable toxicity, withdrawal of consent or decision by the investigator to discontinue treatment. Dose adjustments are based on observed toxicities. Participants who enter in LTE phase will continue to receive the pembrolizumab until 2 years after the first dose of pembrolizumab (at start of study) or until the participant can commercially receive pembrolizumab within the local healthcare system, whichever comes first.


Treatment: Drugs: Erdafitinib
Participants will swallow erdafitinib tablets orally at a starting dose of 8 mg.

Treatment: Drugs: Vinflunine
Participants will receive vinflunine 320 mg/m\^2 as a 20-minute intravenous infusion.

Treatment: Drugs: Docetaxel
Participants will receive docetaxel 75 mg/m\^2 as a 1 hour intravenous infusion.

Treatment: Drugs: Pembrolizumab
Participants will receive pembrolizumab 200 mg as a 30-minute intravenous infusion.

Treatment: Devices: Fibroblast Growth Factor Receptor inhibitor Clinical Trial Assay (FGFRi CTA)
FGFRi CTA will be used to determine molecular eligibility.

Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Treatment: Devices
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Overall Survival (OS)
Timepoint [1] 0 0
Date of first randomization to the date of participant's death (approximately up to 3 years)
Secondary outcome [1] 0 0
Progression-free Survival (PFS)
Timepoint [1] 0 0
Date of randomization to the date of disease progression or relapse from complete response (CR) or death, whichever is reported first (approximately up to 3 years)
Secondary outcome [2] 0 0
Overall Response Rate (ORR)
Timepoint [2] 0 0
Approximately up to 3 years
Secondary outcome [3] 0 0
Change from Baseline in Participant-Reported Health Status and Physical Functioning Scales of the Functional Assessment of Cancer Therapy (FACT-Bl)
Timepoint [3] 0 0
Baseline up to end of treatment (approximately 3 years)
Secondary outcome [4] 0 0
Time Until Symptom Deterioration (Subset of FACT-BI Items)
Timepoint [4] 0 0
Baseline up to end of treatment (approximately 3 years)
Secondary outcome [5] 0 0
Change from Baseline in Patient-Global Impression of Severity (PGIS) Score
Timepoint [5] 0 0
Baseline up to end of treatment (approximately 3 years)
Secondary outcome [6] 0 0
Change from Baseline in the Visual Analog Scale (VAS) of the EQ-5D-5L
Timepoint [6] 0 0
Baseline up to follow up phase (approximately 3 years)
Secondary outcome [7] 0 0
Change from Baseline in the Utility Scale of the EQ-5D-5L
Timepoint [7] 0 0
Baseline up to follow up phase (approximately 3 years)
Secondary outcome [8] 0 0
Duration of Response (DOR)
Timepoint [8] 0 0
From the date of initial documentation of a response to date of first documented evidence of progressive disease (or participants relapse who experience CR during the study) or death (approximately up to 3 years)
Secondary outcome [9] 0 0
Number of Participants with Adverse Events (AEs) as a Measure of Safety
Timepoint [9] 0 0
Approximately up to 3 years
Secondary outcome [10] 0 0
Oral Clearance (CL/F) of Erdafitinib
Timepoint [10] 0 0
Day 14 (Cycle 1), Day 1 (Cycle 2) (each cycle is of 21 days)
Secondary outcome [11] 0 0
Area Under the Plasma Concentration-Time Curve from Time Zero to Time 't' (AUC[0-t]) of Erdafitinib
Timepoint [11] 0 0
Day 14 (Cycle 1), Day 1 (Cycle 2) (each cycle is of 21 days)

Eligibility
Key inclusion criteria
* Histologic demonstration of transitional cell carcinoma of the urothelium. Minor components ( less than [<] 50 percent [%] overall) of variant histology such as glandular or squamous differentiation, or evolution to more aggressive phenotypes such as sarcomatoid or micropapillary change are acceptable
* Metastatic or surgically unresectable urothelial cancer
* Documented progression of disease, defined as any progression that requires a change in treatment, prior to randomization
* Cohort 1: Prior treatment with an anti-PD-(L) 1 agent as monotherapy or as combination therapy; no more than 2 prior lines of systemic treatment. Cohort 2: No prior treatment with an anti-PD-(L) 1 agent; only 1 line of prior systemic treatment. Subjects who received neoadjuvant or adjuvant chemotherapy and showed disease progression within 12 months of the last dose are considered to have received systemic therapy in the metastatic setting.
* A woman of childbearing potential who is sexually active must have a negative pregnancy test (beta human chorionic gonadotropin [beta hCG]) at Screening (urine or serum)
* Participants must meet appropriate molecular eligibility criteria
* Eastern Cooperative Oncology Group (ECOG) performance status Grade 0, 1, or 2
* Adequate bone marrow, liver, and renal function
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Treatment with any other investigational agent or participation in another clinical study with therapeutic intent within 30 days prior to randomization
* Active malignancies (that is, requiring treatment change in the last 24 months). The only allowed exceptions are: urothelial cancer, skin cancer treated within the last 24 months that is considered completely cured, localized prostate cancer with a gleason score of 6 (treated within the last 24 months or untreated and under surveillance) and localized prostate cancer with a gleason score of 3+4 that has been treated more than 6 months prior to full study screening and considered to have a very low risk of recurrence.
* Symptomatic central nervous system metastases
* Received prior fibroblast growth factor receptor (FGFR) inhibitor treatment
* Known allergies, hypersensitivity, or intolerance to erdafitinib or its excipients
* Current central serous retinopathy (CSR) or retinal pigment epithelial detachment of any grade.
* History of uncontrolled cardiovascular disease
* Impaired wound healing capacity defined as skin/decubitus ulcers, chronic leg ulcers, known gastric ulcers, or unhealed incisions

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Chris O'Brien Lifehouse - Camperdown
Recruitment hospital [2] 0 0
Peninsula & South Eastern Haematology and Oncology Group - Frankston
Recruitment hospital [3] 0 0
St George Hospital - Kogarah
Recruitment hospital [4] 0 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment hospital [5] 0 0
Frankston Hospital - Melbourne
Recruitment hospital [6] 0 0
Fiona Stanley Hospital - Murdoch
Recruitment postcode(s) [1] 0 0
2050 - Camperdown
Recruitment postcode(s) [2] 0 0
3199 - Frankston
Recruitment postcode(s) [3] 0 0
2217 - Kogarah
Recruitment postcode(s) [4] 0 0
3000 - Melbourne
Recruitment postcode(s) [5] 0 0
3199 - Melbourne
Recruitment postcode(s) [6] 0 0
6150 - Murdoch
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alaska
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California
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District of Columbia
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Florida
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Georgia
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Illinois
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Kentucky
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Maryland
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Michigan
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Cordoba
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Viedma
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Paris
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Israel
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Israel
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Miyazaki
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Nagoya Shi
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Osaka City
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Osaka
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Sapporo
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Tokyo
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Sutton

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Janssen Research & Development, LLC
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Janssen Research & Development, LLC Clinical Trial
Address 0 0
Janssen Research & Development, LLC
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.