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

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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

Condition: Urothelial Carcinoma

Intervention:

  • Drug: Rogaratinib (BAY1163877)
  • Drug: Atezolizumab
  • Drug: Placebo

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 comprises 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.

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03473756

Sponsor: Bayer

Primary Outcome Measures:

  • Measure: Number of subjects with Dose-limiting toxicities(DLTs) in Part A
  • Time Frame: Up to 21 days
  • Safety Issue:
  • Measure: Number of subjects with treatment-emergent adverse events (TEAEs) in Part A
  • Time Frame: Up to 5 months
  • Safety Issue:
  • Measure: Number of subjects with drug-related TEAEs in Part A
  • Time Frame: Up to 5 months
  • Safety Issue:
  • Measure: Number of subjects with treatment-emergent serious adverse events(TESAEs) in Part A
  • Time Frame: Up to 5 months
  • Safety Issue:
  • Measure: Progression Free Survival(PFS)
  • Time Frame: Up to 25 months
  • Safety Issue:

Secondary Outcome Measures:

  • Measure: Objective Response Rate(ORR) in Part A
  • Time Frame: Up to 5 months
  • Safety Issue:
  • Measure: Maximal plasma concentration (Cmax) of rogaratinib in Part A
  • Time Frame: At cycle 1 Day 1
  • Safety Issue:
  • Measure: Area under the curve(0-8) (AUC(0-8)) of rogaratinib in Part A
  • Time Frame: At cycle 1 Day 1
  • Safety Issue:
  • Measure: Disease Control Rate(DCR) in Part B
  • Time Frame: Up to 25 months
  • Safety Issue:
  • Measure: Duration of Response(DOR) in Part B
  • Time Frame: Up to 25 months
  • Safety Issue:
  • Measure: Overall Survival(OS) in Part B
  • Time Frame: Up to 25 months
  • Safety Issue:
  • Measure: Objective Response Rate (ORR) in Part B
  • Time Frame: Up to 25 months
  • Safety Issue:
  • Measure: Concentrations for rogaratinib in Part B
  • Time Frame: Cycle 1 Day 1(C1D1), C2D1, C3D1, C4D1, C5D1
  • Safety Issue:
  • Measure: Concentrations for atezolizumab in Part B
  • Time Frame: C1D1, C1D15
  • Safety Issue:
  • Measure: Number of subjects with treatment-emergent adverse events (TEAEs) in Part B
  • Time Frame: Up to 25 months
  • Safety Issue:
  • Measure: Number of subjects with drug-related TEAEs in Part B
  • Time Frame: Up to 25 months
  • Safety Issue:
  • Measure: Number of subjects with treatment-emergent serious adverse events(TESAEs) in Part B
  • Time Frame: Up to 25 months
  • Safety Issue:
  • Measure: Number of subjects with significant change in vital signs, physical finding and clinical laboratory results
  • Time Frame: Up to 25 months
  • Safety Issue:

Estimated Enrollment: 210

Study Start Date: May 15, 2018

Phase: Phase 1/Phase 2

Eligibility:

  • Age: minimum 18 Years maximum N/A
  • Gender: All

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. Exlusion 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.

Contact:

  • Bayer Clinical Trials Contact
  • (+) 1-888-8422937

Locations:

  • University of Arizona Cancer Center
  • Tucson Arizona 85724 United States
  • University of California – Davis
  • Sacramento California 95817 United States
  • Comprehensive Cancer Center
  • Chicago Illinois 60637 United States
  • Barbara Ann Karmanos Cancer Institute
  • Detroit Michigan 48201 United States
  • Memorial Sloan-Kettering Cancer Center
  • New York New York 10065 United States
  • Krankenhaus der Elisabethinen Linz GmbH
  • Linz Oberösterreich 4020 Austria
  • Uniklinikum Salzburg – Landeskrankenhaus
  • Salzburg 5020 Austria
  • Krankenhaus der Barmherzigen Brüder
  • Wien 1020 Austria
  • Allgemeines Krankenhaus der Stadt Wien
  • Wien 1090 Austria
  • Institut Bergonié – Unicancer Nouvelle Aquitaine
  • Bordeaux Cedex 33076 France
  • Centre Oscar Lambret – Lille
  • Lille Cedex 59020 France
  • Centre René Gauducheau – Nantes
  • Nantes 44805 France
  • Eberhard-Karls-Universität Tübingen
  • Tübingen Baden-Württemberg 72076 Germany
  • Universitätsklinikum Essen
  • Essen Nordrhein-Westfalen 45122 Germany
  • Universitätsklinikum Köln
  • Köln Nordrhein-Westfalen 50937 Germany
  • Universitätsmedizin der Johannes Gutenberg Universität Mainz
  • Mainz Rheinland-Pfalz 55131 Germany
  • A.O.U. di Modena – Policlinico
  • Modena Emilia-Romagna 41124 Italy
  • Fondazione IRCCS Istituto Nazionale dei Tumori
  • Milano Lombardia 20133 Italy
  • IRCCS Istituto Europeo di Oncologia (IEO)
  • Milano Lombardia 20141 Italy
  • IRCCS Istituto Oncologico Veneto (IOV)
  • Padova Veneto 35128 Italy
  • A.O.U. Integrata Verona
  • Verona Veneto 37134 Italy
  • National Cancer Center Hospital East
  • Kashiwa Chiba 277-8577 Japan
  • National Hospital Organization Shikoku Cancer Center
  • Matsuyama Ehime 791-0280 Japan
  • University of Tsukuba Hospital
  • Tsukuba Ibaraki 305-8576 Japan
  • The Cancer Institute Hospital of JFCR
  • Koto-ku Tokyo 135-8550 Japan
  • Asan Medical Center
  • Seoul 05505 Korea, Republic of
  • Samsung Medical Center
  • Seoul 06351 Korea, Republic of
  • Yonsei University College of Medicine
  • Seoul 120-752 Korea, Republic of
  • Ciutat Sanitària i Universitaria de la Vall d’Hebron
  • Barcelona 08035 Spain
  • Hospital Clínic i Provincial de Barcelona
  • Barcelona 08036 Spain
  • Hospital de la Santa Creu i de Sant Pau
  • Barcelona 08041 Spain
  • Hospital Ramón y Cajal
  • Madrid 28034 Spain
  • Hospital General Universitario de Valencia
  • Valencia 46014 Spain

View trial on ClinicalTrials.gov

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