Back to Clinical Trials

Brief Title: Phase 1b/2 Study of Rogaratinib (BAY1163877) in Combination With Atezolizumab in Urothelial Carcinoma

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

INTRODUCTION

  • Org Study ID: 19131
  • Secondary ID: 2017-001483-38
  • NTC ID: NCT03473756
  • Sponsor: Bayer

BRIEF SUMMARY

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.

  • Overall Status
    Recruiting
  • Start Date
    May 15, 2018
  • Phase
    Phase 1, Phase 2
  • Study Type
    Interventional

PRIMARY OUTCOMES

Primary Outcome 1 - Measure: Number of subjects with Dose-limiting toxicities(DLTs) in Part A

Primary Outcome 1 - Timeframe: Up to 21 days

Primary Outcome 2 - Measure: Number of subjects with treatment-emergent adverse events (TEAEs) in Part A

Primary Outcome 2 - Timeframe: Up to 5 months

Primary Outcome 3 - Measure: Number of subjects with drug-related TEAEs in Part A

Primary Outcome 3 - Timeframe: Up to 5 months

Primary Outcome 4 - Measure: Number of subjects with treatment-emergent serious adverse events(TESAEs) in Part A

Primary Outcome 4 - Timeframe: Up to 5 months

Primary Outcome 5 - Measure: Progression Free Survival(PFS)

Primary Outcome 5 - Timeframe: Up to 25 months

CONDITION

  • Urothelial Carcinoma

ELIGIBILITY

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.

Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No

OFFICIAL INFORMATION

Name: N/A

Role: N/A

Affiliation: N/A

Overall Contact

Name: N/A

Phone: (+) 1-888-8422937

Email: clinical-trials-contact@bayer.com

LOCATION

Facility Status Contact
Facility: University of Arizona Cancer Center
Tucson, Arizona 85724
United States
Status: Recruiting Contact: N/A
Facility: Comprehensive Cancer Center
Chicago, Illinois 60637
United States
Status: Recruiting Contact: N/A
Facility: Barbara Ann Karmanos Cancer Institute
Detroit, Michigan 48201
United States
Status: Recruiting Contact: N/A
Facility: Memorial Sloan-Kettering Cancer Center
New York, New York 10065
United States
Status: Recruiting Contact: N/A
Facility: Ordensklinikum Linz GmbH Elisabethinen
Linz, Oberösterreich 4020
Austria
Status: Recruiting Contact: N/A
Facility: Uniklinikum Salzburg - Landeskrankenhaus
Salzburg, Baden-Württemberg 5020
Austria
Status: Recruiting Contact: N/A
Facility: Krankenhaus der Barmherzigen Brüder
Wien, Nordrhein-Westfalen 1020
Austria
Status: Recruiting Contact: N/A
Facility: Universitätsklinikum AKH Wien
Wien, Nordrhein-Westfalen 1090
Austria
Status: Recruiting Contact: N/A
Facility: Institut Bergonié - Unicancer Nouvelle Aquitaine
Bordeaux Cedex, Rheinland-Pfalz 33076
France
Status: Recruiting Contact: N/A
Facility: Centre Oscar Lambret - Lille
Lille Cedex, Emilia-Romagna 59020
France
Status: Recruiting Contact: N/A
Facility: Institut de Cancérologie de l'Ouest - Saint Herblain
Nantes, Lombardia 44805
France
Status: Recruiting Contact: N/A
Facility: Universitätsklinikum Essen
Essen, Veneto 45122
Germany
Status: Recruiting Contact: N/A
Facility: Universitätsklinikum Köln
Köln, Veneto 50937
Germany
Status: Recruiting Contact: N/A
Facility: Universitätsmedizin der Johannes Gutenberg Universität Mainz
Mainz, Chiba 55131
Germany
Status: Recruiting Contact: N/A
Facility: Fondazione IRCCS Istituto Nazionale dei Tumori
Milano, Ibaraki 20133
Italy
Status: Recruiting Contact: N/A
Facility: IRCCS Istituto Europeo di Oncologia s.r.l. (IEO)
Milano, Tokyo 20141
Italy
Status: Recruiting Contact: N/A
Facility: Istituto Oncologico Veneto IRCCS (IOV)
Padova, 35128
Italy
Status: Recruiting Contact: N/A
Facility: A.O.U.I. Verona
Verona, 37134
Italy
Status: Recruiting Contact: N/A
Facility: Severance Hospital, Yonsei University Health System
Seoul, 03722
Korea, Republic of
Status: Recruiting Contact: N/A
Facility: Asan Medical Center
Seoul, 05505
Korea, Republic of
Status: Recruiting Contact: N/A
Facility: Samsung Medical Center
Seoul, 06351
Korea, Republic of
Status: Recruiting Contact: N/A
Facility: Ciutat Sanitària i Universitaria de la Vall d'Hebron
Barcelona, 08035
Spain
Status: Recruiting Contact: N/A
Facility: Hospital Clínic i Provincial de Barcelona
Barcelona, 08036
Spain
Status: Recruiting Contact: N/A
Facility: Hospital Ramón y Cajal
Madrid, 28034
Spain
Status: Recruiting Contact: N/A
Facility: Hospital General Universitario de Valencia
Valencia, 46014
Spain
Status: Recruiting Contact: N/A