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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03410693




Registration number
NCT03410693
Ethics application status
Date submitted
19/01/2018
Date registered
19/01/2018
Date last updated
22/01/2019

Titles & IDs
Public title
Study of Rogaratinib (BAY1163877) vs Chemotherapy in Patients With FGFR (Fibroblast Growth Factor Receptor)-Positive Locally Advanced or Metastatic Urothelial Carcinoma
Scientific title
A Randomized, Open Label, Multicenter Phase 2/3 Study to Evaluate the Efficacy and Safety of Rogaratinib (BAY1163877) Compared to Chemotherapy in Patients With FGFR-positive Locally Advanced or Metastatic Urothelial Carcinoma Who Have Received Prior Platinum-containing Chemotherapy
Secondary ID [1] 0 0
2016-004340-11
Secondary ID [2] 0 0
17403
Universal Trial Number (UTN)
Trial acronym
FORT-1
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Carcinoma, Transitional Cell 0 0
Condition category
Condition code
Cancer 0 0 0 0
Non melanoma skin cancer
Cancer 0 0 0 0
Kidney
Cancer 0 0 0 0
Bladder - transitional cell cancer

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Rogaratinib (BAY1163877)
Treatment: Drugs - Chemotherapy

Experimental: Rogaratinib - Rogaratinib treatment study arm, comprising
Pre-treatment period, including FGFR testing and screening,
Treatment period, and
Follow-up period, including active follow-up and long-term follow-up. Patients will be considered "on study" during the pre-treatment, treatment and active followup periods. During the long-term follow-up period the patients will be considered "off study".

Active Comparator: Chemotherapy - Chemotherapy treatment study arm, comprising
Pre-treatment period, including FGFR testing and screening,
Treatment period, and
Follow-up period, including active follow-up and long-term follow-up. Patients will be considered "on study" during the pre-treatment, treatment and active followup periods. During the long-term follow-up period the patients will be considered "off study".


Treatment: Drugs: Rogaratinib (BAY1163877)
Rogaratinib administered as oral (p.o.) tablets twice daily (b.i.d.) continuously

Treatment: Drugs: Chemotherapy
Chemotherapy as taxane (docetaxel or paclitaxel) or vinflunine administered through intravenous (i.v.) infusion every 3 weeks (on day 1 of a 21-day cycle) The choice of the chemotherapy is at the discretion of the investigator, taking into consideration the status of the authorization in the given Country (i.e. the drug has to be approved at least for one indication in the given country).

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

Outcomes
Primary outcome [1] 0 0
Overall Survival - Defined as the time (days) from randomization to death due to any cause. Patients alive at the date of data cut-off for analysis will be censored at the last date known to be alive.
Timepoint [1] 0 0
Up to 45 months
Secondary outcome [1] 0 0
Progression-free survival (PFS) - Defined as the time (days) from randomization to date of first observed disease progression (radiological or clinical assessment) or death due to any cause, if death occurs before progression is documented. For patients without documented radiological or clinical progression or death at the time of analysis, PFS will be censored at the last actual visit date of tumor evaluation.
Timepoint [1] 0 0
Up to 45 months
Secondary outcome [2] 0 0
Objective response rate (ORR) - Defined as the percentage of patients with complete response (CR) or partial Response (PR). Patients for whom overall best response is not CR or PR, as well as patients without any post-baseline tumor assessment will be considered non-responders.
Timepoint [2] 0 0
Up to 45 months
Secondary outcome [3] 0 0
Disease-control rate (DCR) - Defined as the percentage of patients, whose overall best response was not progressive disease [PD] (i.e. CR, PR, Stable Disease [SD] or Non CR/Non PD). Tumor assessments with SD as response, that is performed prematurely after randomization of the patient (i.e. substantially earlier than the first planned radiological tumor assessment at 6 weeks), will not be taken into account.
Timepoint [3] 0 0
Up to 45 months
Secondary outcome [4] 0 0
Duration of response (DOR) - Defined as the time from the first documented objective response of PR or CR, whichever is noted earlier, to disease progression or death (if death occurs before progression is documented). DOR will be defined for responders only, i.e. patients with a CR or PR.
Timepoint [4] 0 0
Up to 45 months
Secondary outcome [5] 0 0
Incidence of Adverse Events as a measure of safety and tolerability
Timepoint [5] 0 0
Up to 45 months

Eligibility
Key inclusion criteria
- Existence of archival or fresh biopsy for FGFR testing

- FGFR testing of patients will be performed at the investigators' discretion up to a
max. of 90 days prior to start of screening.

Investigators should ensure all patients will be eligible in terms of disease status and
lines of treatment within this timeframe.

- Documented urothelial carcinoma (transitional cell carcinoma) including urinary
bladder, renal pelvis, ureters, urethra meeting all of the following criteria

- Histologically or cytologically confirmed (patients with mixed histologies are
required to have a dominant transitional cell pattern.)

- Locally advanced (T4b, any N; or any T, N 2-3) or metastatic disease (any T, any
N and M1). Locally advanced bladder cancer must be unresectable i.e. invading the
pelvic or abdominal wall (stage T4b) or presenting with bulky nodal disease
(N2-3).

- ECOG (Eastern Cooperative Oncology Group) Performance Status of 0 or 1

- Disease progression during or following treatment with at least one
platinum-containing regimen (patients should have been treated for at least 2 cycles).
In patients who received prior adjuvant/neoadjuvant platinum-containing chemotherapy,
progression had to occur within 12 months of treatment.

- High FGFR1 or 3 mRNA (Messenger ribonucleic acid) expression levels (RNAscope score of
3+ or 4+; measurement is part of this protocol) in archival or fresh Tumor biopsy
specimen

- At least 1 measurable lesion according to Response Evaluation Criteria in Solid Tumors
(RECIST v.1.1) in contrast enhanced (unless contraindicated) CT or MRI
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Previous or concurrent cancer except

- cervical carcinoma in situ

- treated basal-cell or squamous cell skin carcinoma

- any cancer curatively treated > 3 years before randomization

- Curatively treated incidental prostate cancer (T1/T2a)

- Ongoing or previous anti-cancer treatment within 4 weeks before randomization.

- More than two prior lines of systemic anti-cancer therapy for urothelial carcinoma

- Ongoing or previous treatment with anti-FGFR directed therapies (e.g. receptor
tyrosine kinase inhibitors including rogaratinib or FGFRspecific antibodies) or with
taxanes or vinflunine

- Unresolved toxicity higher than National Cancer Institute's Common Terminology
Criteria for Adverse Events, version 4.03 (CTCAE v.4.03) Grade 1 attributed to any
prior therapy/procedure excluding alopecia, anemia and/or hypothyroidism

- History or current condition of an uncontrolled cardiovascular disease including any
of the following conditions:

- Congestive heart failure (CHF) NYHA (New York Heart Association) > Class 2

- Unstable angina (symptoms of angina at rest) or new-onset angina (within last 3
months before randomization)

- Myocardial infarction (MI) within past 6 months before randomization

- Unstable cardiac arrhythmias requiring anti-arrhythmic therapy. Patients with
arrhythmia under control with anti-arrhythmic therapy such as beta-blockers or
digoxin are eligible.

- Arterial or venous thrombotic events or embolic events such as cerebrovascular
accident (including transient ischemic attacks), deep vein thrombosis or pulmonary
embolism within 3 months before randomization

- Current evidence of endocrine alteration of calcium Phosphate homeostasis (e.g.
parathyroid disorder, history of parathyroidectomy, tumor lysis, tumoral calcinosis,
paraneoplastic hypercalcemia)

- Any hemorrhage / bleeding event = CTCAE v.4.03 Grade 3 within 4 weeks before
randomization

- Current diagnosis of any retinal detachment, retinal pigment epithelial detachment
(RPED), serous retinopathy or retinal vein occlusion

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 2/Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
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)
NSW,QLD,VIC
Recruitment hospital [1] 0 0
Mid North Coast Cancer Institute - Coffs Harbour
Recruitment hospital [2] 0 0
Northern Cancer Institute - St Leonards
Recruitment hospital [3] 0 0
Macquarie University Hospital - Sydney
Recruitment hospital [4] 0 0
Riverina Cancer Care Centre - Wagga Wagga
Recruitment hospital [5] 0 0
Sydney Adventist Hospital - Wahroonga
Recruitment hospital [6] 0 0
Pindara Private Hospital - Benowa
Recruitment hospital [7] 0 0
Monash Medical Centre - Clayton
Recruitment postcode(s) [1] 0 0
2450 - Coffs Harbour
Recruitment postcode(s) [2] 0 0
2065 - St Leonards
Recruitment postcode(s) [3] 0 0
2109 - Sydney
Recruitment postcode(s) [4] 0 0
2650 - Wagga Wagga
Recruitment postcode(s) [5] 0 0
2076 - Wahroonga
Recruitment postcode(s) [6] 0 0
4217 - Benowa
Recruitment postcode(s) [7] 0 0
3168 - Clayton
Recruitment outside Australia
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United States of America
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Alaska
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Arizona
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Valencia
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Somerset
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London

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Bayer
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This is a randomized, open-label, multicenter Phase 2/3 study to evaluate the efficacy and
safety of rogaratinib (BAY 1163877) compared to chemotherapy in patients with FGFRpositive
locally advanced or metastatic urothelial carcinoma who have received Prior
platinum-containing chemotherapy.

The primary objective of the entire study is to compare rogaratinib (BAY1163877) with
chemotherapy (docetaxel, paclitaxel or vinflunine) in terms of prolonging the Overall
survival (OS) of patients with FGFR positive urothelial carcinoma.

At randomization, patients will have locally advanced or metastatic urothelial carcinoma and
have received at least one prior platinum-containing chemotherapy regimen. Only patients with
FGFR1 or 3 positive tumors can be randomized into the study. Archival tumor tissue is
adequate for testing of FGFR1 and 3 mRNA expressions, which will be determined centrally
using an RNA in situ hybridization (RNA-ISH) test. Approximately 42 % of UC patients with
locally advanced or metastatic UC are identified as FGFR-positive by the RNA-ISH cut-off
applied.
Trial website
https://clinicaltrials.gov/show/NCT03410693
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Bayer Study Director
Address 0 0
Bayer
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Bayer Clinical Trials Contact
Address 0 0
Country 0 0
Phone 0 0
(+) 1-888-8422937
Fax 0 0
Email 0 0
clinical-trials-contact@bayer.com
Contact person for scientific queries

No data has been provided for results reporting
Summary results
Not applicable