Trial Review

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 endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT03410693




Registration number
NCT03410693
Ethics application status
Date submitted
19/01/2018
Date registered
25/01/2018
Date last updated
28/09/2022

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 or treatment guidelines in the given country.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Objective Response Rate (ORR) - Central Assessment
Timepoint [1] 0 0
From start of treatment up to end of active follow-up, approximately 29 months
Secondary outcome [1] 0 0
Disease-control Rate (DCR) - Central Assessment
Timepoint [1] 0 0
From start of treatment till end of active follow-up, approximately 29 months
Secondary outcome [2] 0 0
Progression-free Survival (PFS) - Central Assessment
Timepoint [2] 0 0
From start of treatment till end of active follow-up, approximately 29 months
Secondary outcome [3] 0 0
Duration of Response (DOR) - Central Assessment
Timepoint [3] 0 0
From start of treatment till end of active follow-up, approximately 29 months
Secondary outcome [4] 0 0
Number of Participants With Treatment Emergent Adverse Events
Timepoint [4] 0 0
From start of treatment up to 30 days after the last administration of study treatment, approximately 29 months

Eligibility
Key inclusion criteria
- Existence of archival or fresh biopsy for FGFR testing. Mandatory FGFR testing of
patients will be performed prior to start of screening. The timing of the FGFR test is
at the discretion of the investigator. Investigators should ensure all patients will
be eligible in terms of disease status and lines of treatment.

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

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

- Locally advanced (T4, 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 expression levels in archival or fresh tumor biopsy specimen
quantified as outlined in the lab manual

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

- More than two prior lines of systemic anti-cancer therapy for urothelial carcinoma
given for advanced unresectable/ metastatic disease

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

- 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)

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

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

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
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
31/05/2018
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
27/10/2020
Sample size
Target
Accrual to date
Final
175
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
Country [1] 0 0
United States of America
State/province [1] 0 0
Alaska
Country [2] 0 0
United States of America
State/province [2] 0 0
Arizona
Country [3] 0 0
United States of America
State/province [3] 0 0
California
Country [4] 0 0
United States of America
State/province [4] 0 0
Colorado
Country [5] 0 0
United States of America
State/province [5] 0 0
Florida
Country [6] 0 0
United States of America
State/province [6] 0 0
Kansas
Country [7] 0 0
United States of America
State/province [7] 0 0
Nevada
Country [8] 0 0
United States of America
State/province [8] 0 0
Oregon
Country [9] 0 0
United States of America
State/province [9] 0 0
Pennsylvania
Country [10] 0 0
United States of America
State/province [10] 0 0
South Carolina
Country [11] 0 0
United States of America
State/province [11] 0 0
Texas
Country [12] 0 0
United States of America
State/province [12] 0 0
Washington
Country [13] 0 0
Austria
State/province [13] 0 0
Krems
Country [14] 0 0
Austria
State/province [14] 0 0
Wien
Country [15] 0 0
Belgium
State/province [15] 0 0
Gent
Country [16] 0 0
Belgium
State/province [16] 0 0
Leuven
Country [17] 0 0
Belgium
State/province [17] 0 0
Ottignies
Country [18] 0 0
Canada
State/province [18] 0 0
Ontario
Country [19] 0 0
Canada
State/province [19] 0 0
Quebec
Country [20] 0 0
Canada
State/province [20] 0 0
Ottawa
Country [21] 0 0
China
State/province [21] 0 0
Fujian
Country [22] 0 0
China
State/province [22] 0 0
Guangdong
Country [23] 0 0
China
State/province [23] 0 0
Hubei
Country [24] 0 0
China
State/province [24] 0 0
Jiangsu
Country [25] 0 0
China
State/province [25] 0 0
Liaoning
Country [26] 0 0
China
State/province [26] 0 0
Beijing
Country [27] 0 0
China
State/province [27] 0 0
Guangzhou
Country [28] 0 0
China
State/province [28] 0 0
Shanghai
Country [29] 0 0
Czechia
State/province [29] 0 0
Ostrava
Country [30] 0 0
Czechia
State/province [30] 0 0
Praha 10
Country [31] 0 0
Czechia
State/province [31] 0 0
Praha 4 - Krc
Country [32] 0 0
Czechia
State/province [32] 0 0
Zlin
Country [33] 0 0
Denmark
State/province [33] 0 0
Aarhus N
Country [34] 0 0
Denmark
State/province [34] 0 0
Herlev
Country [35] 0 0
Denmark
State/province [35] 0 0
København
Country [36] 0 0
Finland
State/province [36] 0 0
Helsinki
Country [37] 0 0
France
State/province [37] 0 0
Besancon
Country [38] 0 0
France
State/province [38] 0 0
Bordeaux
Country [39] 0 0
France
State/province [39] 0 0
Caen Cedex 5
Country [40] 0 0
France
State/province [40] 0 0
Clermont Ferrand Cedex 1
Country [41] 0 0
France
State/province [41] 0 0
Lille Cedex
Country [42] 0 0
France
State/province [42] 0 0
Lyon Cedex
Country [43] 0 0
France
State/province [43] 0 0
Marseille
Country [44] 0 0
France
State/province [44] 0 0
Paris
Country [45] 0 0
France
State/province [45] 0 0
Saint Mande
Country [46] 0 0
France
State/province [46] 0 0
Strasbourg
Country [47] 0 0
France
State/province [47] 0 0
Suresnes
Country [48] 0 0
Germany
State/province [48] 0 0
Baden-Württemberg
Country [49] 0 0
Germany
State/province [49] 0 0
Nordrhein-Westfalen
Country [50] 0 0
Germany
State/province [50] 0 0
Rheinland-Pfalz
Country [51] 0 0
Hong Kong
State/province [51] 0 0
Shatin
Country [52] 0 0
Hungary
State/province [52] 0 0
Budapest
Country [53] 0 0
Hungary
State/province [53] 0 0
Pecs
Country [54] 0 0
Ireland
State/province [54] 0 0
Cork
Country [55] 0 0
Ireland
State/province [55] 0 0
Dublin
Country [56] 0 0
Israel
State/province [56] 0 0
Haifa
Country [57] 0 0
Israel
State/province [57] 0 0
Jerusalem
Country [58] 0 0
Israel
State/province [58] 0 0
Kfar Saba
Country [59] 0 0
Israel
State/province [59] 0 0
Petah Tikva
Country [60] 0 0
Israel
State/province [60] 0 0
Ramat Gan
Country [61] 0 0
Italy
State/province [61] 0 0
Emilia-Romagna
Country [62] 0 0
Italy
State/province [62] 0 0
Lazio
Country [63] 0 0
Italy
State/province [63] 0 0
Lombardia
Country [64] 0 0
Italy
State/province [64] 0 0
Piemonte
Country [65] 0 0
Italy
State/province [65] 0 0
Toscana
Country [66] 0 0
Italy
State/province [66] 0 0
Veneto
Country [67] 0 0
Japan
State/province [67] 0 0
Aichi
Country [68] 0 0
Japan
State/province [68] 0 0
Aomori
Country [69] 0 0
Japan
State/province [69] 0 0
Gunma
Country [70] 0 0
Japan
State/province [70] 0 0
Hokkaido
Country [71] 0 0
Japan
State/province [71] 0 0
Hyogo
Country [72] 0 0
Japan
State/province [72] 0 0
Ibaraki
Country [73] 0 0
Japan
State/province [73] 0 0
Iwate
Country [74] 0 0
Japan
State/province [74] 0 0
Kanagawa
Country [75] 0 0
Japan
State/province [75] 0 0
Osaka
Country [76] 0 0
Japan
State/province [76] 0 0
Saitama
Country [77] 0 0
Japan
State/province [77] 0 0
Tokyo
Country [78] 0 0
Japan
State/province [78] 0 0
Akita
Country [79] 0 0
Japan
State/province [79] 0 0
Fukuoka
Country [80] 0 0
Japan
State/province [80] 0 0
Hiroshima
Country [81] 0 0
Japan
State/province [81] 0 0
Kumamoto
Country [82] 0 0
Japan
State/province [82] 0 0
Niigata
Country [83] 0 0
Japan
State/province [83] 0 0
Toyama
Country [84] 0 0
Korea, Republic of
State/province [84] 0 0
Gyeonggido
Country [85] 0 0
Korea, Republic of
State/province [85] 0 0
Seoul
Country [86] 0 0
Netherlands
State/province [86] 0 0
Amsterdam
Country [87] 0 0
Netherlands
State/province [87] 0 0
Rotterdam
Country [88] 0 0
Poland
State/province [88] 0 0
Bydgoszcz
Country [89] 0 0
Poland
State/province [89] 0 0
Kielce
Country [90] 0 0
Poland
State/province [90] 0 0
Konin
Country [91] 0 0
Poland
State/province [91] 0 0
Olsztyn
Country [92] 0 0
Poland
State/province [92] 0 0
Poznan
Country [93] 0 0
Poland
State/province [93] 0 0
Wroclaw
Country [94] 0 0
Portugal
State/province [94] 0 0
Lisboa
Country [95] 0 0
Portugal
State/province [95] 0 0
Coimbra
Country [96] 0 0
Portugal
State/province [96] 0 0
Porto
Country [97] 0 0
Russian Federation
State/province [97] 0 0
Krasnoyarsk
Country [98] 0 0
Russian Federation
State/province [98] 0 0
Moscow
Country [99] 0 0
Russian Federation
State/province [99] 0 0
Nizhny Novgorod
Country [100] 0 0
Russian Federation
State/province [100] 0 0
Omsk
Country [101] 0 0
Russian Federation
State/province [101] 0 0
Ufa
Country [102] 0 0
Singapore
State/province [102] 0 0
Singapore
Country [103] 0 0
Slovakia
State/province [103] 0 0
Bratislava
Country [104] 0 0
Slovakia
State/province [104] 0 0
Nitra
Country [105] 0 0
Slovakia
State/province [105] 0 0
Poprad
Country [106] 0 0
Spain
State/province [106] 0 0
Barcelona
Country [107] 0 0
Spain
State/province [107] 0 0
Illes Baleares
Country [108] 0 0
Spain
State/province [108] 0 0
Cáceres
Country [109] 0 0
Spain
State/province [109] 0 0
Córdoba
Country [110] 0 0
Spain
State/province [110] 0 0
Madrid
Country [111] 0 0
Spain
State/province [111] 0 0
Málaga
Country [112] 0 0
Spain
State/province [112] 0 0
Valencia
Country [113] 0 0
Sweden
State/province [113] 0 0
Stockholm
Country [114] 0 0
Switzerland
State/province [114] 0 0
Basel-Stadt
Country [115] 0 0
Switzerland
State/province [115] 0 0
Graubünden
Country [116] 0 0
Switzerland
State/province [116] 0 0
Sankt Gallen
Country [117] 0 0
Taiwan
State/province [117] 0 0
Taichung
Country [118] 0 0
Taiwan
State/province [118] 0 0
Tainan
Country [119] 0 0
Taiwan
State/province [119] 0 0
Taipei
Country [120] 0 0
Taiwan
State/province [120] 0 0
Taoyuan
Country [121] 0 0
United Kingdom
State/province [121] 0 0
Merseyside
Country [122] 0 0
United Kingdom
State/province [122] 0 0
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 FGFR-positive
locally advanced or metastatic urothelial carcinoma who have received prior
platinum-containing chemotherapy.

The primary objective is to demonstrate the superiority of rogaratinib over chemotherapy in
terms of objective response rate (before: overall survivial) of urothelial carcinoma patients
with FGFR positive tumors.

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/ct2/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
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT03410693