check_circleStudy Completed

Urothelial Carcinoma

Phase 1b/2 study of rogaratinib (BAY1163877) in combination with atezolizumab in urothelial carcinoma

Trial purpose

FORT-2 is designed to evaluate safety, efficacy, RP2D and PK of rogaratinib in combination with atezolizumab in patients with untreated FGFR-positive urothelial carcinoma. The study originally comprised two separate parts: Phase 1b (Part A) and Phase 2 (Part B). The study parts differ in design, objectives, and treatment.
The primary objectives of this Phase 1b study (Part A) are to determine the safety, tolerability, RP2D and pharmacokinetics of rogaratinib in combination with atezolizumab in these patients.
The primary objective of the Part B is to compare progression-free survival (PFS) according to RECIST v1.1 of rogaratinib in combination with atezolizumab over placebo in combination with atezolizumab in untreated patients with FGFR-positive locally advanced or metastatic urothelial carcinoma.
Of note, patients who participate in Part A are not allowed to participate in Part B.
Part B will be initiated once the data from Part A supports continuation of the study, even if this occurs prior to primary completion of Part A. The sponsor may decide not to continue the study as a whole after completion of Part A if the data do not support further development.
Part B of the study will no longer be conducted.

Key Participants Requirements

Sex

All

Age

18 - N/A
  • Inclusion criteria:
    - Existence of archival or fresh tumor biopsy specimen for FGFR1/3 mRNA expression testing
    - High FGFR1 or 3 mRNA expression levels (RNAscope score of 3+ or 4+) in archival or fresh tumor biopsy specimen
    - Documented locally advanced (T4, any N; or any T, N2-3) or metastatic urothelial carcinoma (transitional cell carcinoma) including urinary bladder, renal pelvis, ureters, urethra, meeting all of the following criteria:
    - No prior systemic treatment for locally advanced or metastatic urothelial carcinoma. For patients who received prior adjuvant/neoadjuvant chemotherapy or chemo-radiation for urothelial carcinoma, a treatment-free interval > 12 months between the last treatment administration and the date of recurrence is required in order to be considered treatment-naïve in the metastatic setting. Prior local intra-vesical chemotherapy or prior local immunotherapy is allowed if completed at least 4 weeks before the first study drug administration. Regionally available standard of care options must
    be considered for all patients.
    - Ineligibility for cisplatin-based chemotherapy as defined by any one of the following criteria:
     -- Impaired renal function (GFR > 30 but < 60 mL/min/1.73 m2) according to the modification of diet in renal disease (MDRD) abbreviated formula
     -- A Hearing loss (measured by audiometry) of > 25 dB at two contiguous test frequencies in at least one ear.
     -- Grade ≥ 2 peripheral neuropathy (i.e. sensory alteration or paresthesia including tingling)
    - Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0 or 1.
    Exclusion criteria:
    - Active symptomatic or untreated brain metastases as determined by CT or MRI evaluation during screening and prior radiographic assessment.
    - History of autoimmune disease, including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with anti-phospholipid syndrome, granulomatosis with polyangiitis, Sjögren’s syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis.
    - History or current condition of an uncontrolled cardiovascular disease including any of the following conditions:
     -- Congestive heart failure (CHF) NYHA Class 2 or greater, unstable angina (symptoms of angina at rest) or
     -- New-onset angina (within last 3 months before the first study drug administration)
     -- Myocardial infarction (MI) within past 6 months before the first study drug administration
     -- Unstable cardiac arrhythmias requiring anti-arrhythmic therapy.
    - Patients with known coronary artery disease, congestive heart failure not meeting the above criteria, or known left ventricular ejection fraction < 50% must be on a stable medical regimen that is optimized in the opinion of the treating physician, in consultation with a cardiologist if appropriate.
    - Current diagnosis of any retinal disorders including retinal detachment, retinal pigment epithelial detachment (RPED), serous retinopathy or retinal vein occlusion.
    - Current evidence of endocrine alteration of calcium phosphate homeostasis (e.g. parathyroid disorder, history of parathyroidectomy, tumor lysis, tumoral calcinosis, paraneoplastic hypercalcemia).
    - Concomitant therapies that are known to increase serum calcium or phosphate levels (i.e. antacids, phosphate-containing laxatives oral/rectal, potassium phosphate) and that cannot be discontinued or switched to a different medication before the first study drug administration
    - Treatment with systemic corticosteroids or other systemic immunosuppressant medications within 2 weeks before the first study drug administration, or anticipated requirement for systemic immunosuppressive medications during the trial.

Trial summary

Enrollment Goal
37
Trial Dates
May 2018 - July 2024
Phase
Phase 1
Could I Receive a placebo
No
Products
Rogaratinib (BAY1163877)
Accepts Healthy Volunteer
No

Where to participate

StatusInstitutionLocation
Completed
Centre Oscar Lambret - LilleLILLE CEDEX, 59020, France
Completed
Institut Bergonie - Unicancer Nouvelle AquitaineBORDEAUX CEDEX, 33076, France
Completed
Institut de Cancérologie de l'Ouest - Saint HerblainSaint-Herblain, 44800, France
Completed
Ciutat Sanitaria i Universitaria de la Vall d'HebronBarcelona, 08035, Spain
Withdrawn
Hospital de la Santa Creu i de Sant Pau | OncologíaBarcelona, 8041, Spain
Completed
Hospital General Universitario de ValenciaValencia, 46014, Spain
Completed
Hospital Ramón y Cajal | OncologíaMadrid, 28034, Spain
Completed
Severance Hospital, Yonsei University Health SystemSeoul, 03722, Korea,_republic_of
Completed
Asan Medical CenterSeoul, 05505, Korea,_republic_of
Completed
Universitätsklinikum AKH WienWien, 1090, Austria
Completed
Krankenhaus der Barmherzigen BrüderVienna, 1020, Austria
Completed
Ordensklinikum Linz GmbH ElisabethinenLinz, 4020, Austria
Completed
Uniklinikum Salzburg - LandeskrankenhausSalzburg, 5020, Austria
Completed
Fondazione IRCCS Istituto Nazionale dei TumoriMilano, 20133, Italy
Completed
Azienda Ospedaliero Universitaria di ModenaModena, 41100, Italy
Completed
Istituto Europeo di Oncologia s.r.l - Sviluppo di nuovi farmaci per Terapie InnovativeMilano, 20141, Italy
Completed
A.O.U.I. VeronaVerona, 37134, Italy
Completed
Istituto Oncologico VenetoPadova, 35128, Italy
Completed
Universitätsklinikum EssenEssen, 45147, Germany
Completed
Universitätsklinikum KölnKöln, 50937, Germany
Withdrawn
Eberhard-Karls-Universität TübingenTübingen, 72076, Germany
Completed
Universitätsmedizin der Johannes Gutenberg Universität MainzMainz, 55101, Germany
Completed
University of Arizona Cancer CenterTucson, 85724, United States
Withdrawn
University of California - DavisSacramento, 95817, United States
Completed
Barbara Ann Karmanos Cancer Institute - Detroit HeadquartersDetroit, 48201, United States
Completed
Memorial Sloan-Kettering Cancer CenterNew York, 10065, United States
Completed
UChicago Medicine Comprehensive Cancer Center - Hyde ParkChicago, 60637, United States
Completed
Samsung Medical CenterSeoul, 06351, Korea,_republic_of
Completed
University of Tsukuba HospitalTsukuba, 305-8576, Japan
Completed
The Cancer Institute Hospital of JFCRKoto-ku, 135-8550, Japan
Completed
National Cancer Center Hospital EastKashiwa, 277-8577, Japan
Completed
National Hospital Organization Shikoku Cancer CenterMatsuyama, 791-0280, Japan
Completed
Hospital Clínic i Provincial de BarcelonaBarcelona, 8036, Spain

Primary Outcome

  • Number of participants with Dose-limiting toxicities(DLTs)
    date_rangeTime Frame:
    Up to 21 days
  • Number of participants with treatment-emergent adverse events (TEAEs)
    date_rangeTime Frame:
    Up to 30 days after the last dose of rogaratinib or 90 days after the last atezolizumab administration, whichever comes later
  • Number of participants with drug-related TEAEs
    date_rangeTime Frame:
    Up to 30 days after the last dose of rogaratinib or 90 days after the last atezolizumab administration, whichever comes later
  • Number of participants with treatment-emergent serious adverse events(TESAEs)
    date_rangeTime Frame:
    Up to 30 days after the last dose of rogaratinib or 90 days after the last atezolizumab administration, whichever comes later

Secondary Outcome

  • Objective Response Rate(ORR)
    Objective response rate (ORR) was defined as the percentage of patients with complete response (CR) or partial response (PR). Patients for whom best overall tumor response was not CR or PR, as well as patients without any post-baseline tumor assessment were considered non-responders. For all patients, the best overall tumor response was determined locally by investigators using the RECIST (Response Evaluation Criteria In Solid Tumors) criteria.
    date_rangeTime Frame:
    Up to 5 months
  • Maximal plasma concentration (Cmax) of rogaratinib
    date_rangeTime Frame:
    At cycle 1 Day 1
  • Area under the rogaratinib concentration versus time curve (AUC)
    date_rangeTime Frame:
    At cycle 1 Day 1, 0-t(last)

Trial design

An international, multicenter, Phase 1b/2 study of rogaratinib (BAY1163877) in combination with atezolizumab as first-line treatment in cisplatin-ineligible patients with FGFR-positive locally advanced or metastatic urothelial carcinoma
Trial Type
Interventional
Intervention Type
Drug
Trial Purpose
Treatment
Allocation
N/A
Blinding
N/A
Assignment
Single Group Assignment
Trial Arms
1