Trial Condition(s):

Urothelial Carcinoma

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

Bayer Identifier:

19131

ClinicalTrials.gov Identifier:

NCT03473756

EudraCT Number:

2017-001483-38

Recruitment Complete

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.

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.
Exclusion Criteria
No Exclusion Criteria Available

Trial Summary

Enrollment Goal
37
Trial Dates
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Phase
1
Could I receive a placebo?
No
Products
Rogaratinib (BAY1163877)
Accepts Healthy Volunteers
No

Where to Participate

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Locations
Status
LocationsStatus
Locations

Centre Oscar Lambret - Lille

LILLE CEDEX, France, 59020

Status
Active, not recruiting
 
Locations

Institut Bergonié - Unicancer Nouvelle Aquitaine

BORDEAUX CEDEX, France, 33076

Status
Completed
 
Locations

Institut de Cancérologie de l'Ouest - Saint Herblain

NANTES, France, 44805

Status
Active, not recruiting
 
Locations

Ciutat Sanitaria i Universitaria de la Vall d'Hebron

Barcelona, Spain, 08023

Status
Completed
 
Locations

Hospital General Universitario de Valencia

Valencia, Spain, 46014

Status
Completed
 
Locations

Hospital Ramón y Cajal | Oncología

Madrid, Spain, 28034

Status
Active, not recruiting
 
Locations

Severance Hospital, Yonsei University Health System

Seoul, South Korea, 03722

Status
Completed
 
Locations

Asan Medical Center

Seoul, South Korea, 05505

Status
Active, not recruiting
 
Locations

Universitätsklinikum AKH Wien

Wien, Austria, 1090

Status
Completed
 
Locations

Krankenhaus der Barmherzigen Brüder

Wien, Austria, 1020

Status
Active, not recruiting
 
Locations

Ordensklinikum Linz GmbH Elisabethinen

Linz, Austria, 4020

Status
Active, not recruiting
 
Locations

Uniklinikum Salzburg - Landeskrankenhaus

Salzburg, Austria, 5020

Status
Completed
 
Locations

Fondazione IRCCS Istituto Nazionale dei Tumori

Milano, Italy, 20133

Status
Active, not recruiting
 
Locations

A.O.U. di Modena - Policlinico

Modena, Italy, 41124

Status
Completed
 
Locations

IRCCS Istituto Europeo di Oncologia s.r.l. (IEO)

Milano, Italy, 20141

Status
Active, not recruiting
 
Locations

A.O.U.I. Verona

Verona, Italy, 37134

Status
Completed
 
Locations

Istituto Oncologico Veneto IRCCS (IOV)

Padova, Italy, 35128

Status
Completed
 
Locations

Universitätsklinikum Essen

Essen, Germany, 45122

Status
Active, not recruiting
 
Locations

Universitätsklinikum Köln

Köln, Germany, 50937

Status
Completed
 
Locations

Universitätsmedizin der Johannes Gutenberg Universität Mainz

Mainz, Germany, 55131

Status
Completed
 
Locations

University of Arizona Cancer Center

Tucson, United States, 85724

Status
Completed
 
Locations

Barbara Ann Karmanos Cancer Institute - Detroit

Detroit, United States, 48201

Status
Completed
 
Locations

Memorial Sloan-Kettering Cancer Center

New York, United States, 10065

Status
Completed
 
Locations

Comprehensive Cancer Center

Chicago, United States, 60637

Status
Active, not recruiting
 
Locations

Samsung Medical Center

Seoul, South Korea, 06351

Status
Completed
 
Locations

University of Tsukuba Hospital

Tsukuba, Japan, 305-8576

Status
Completed
 
Locations

The Cancer Institute Hospital of JFCR

Koto-ku, Japan, 135-8550

Status
Completed
 
Locations

National Cancer Center Hospital East

Kashiwa, Japan, 277-8577

Status
Completed
 
Locations

National Hospital Organization Shikoku Cancer Center

Matsuyama, Japan, 791-0280

Status
Completed
 
Locations

Hospital Clínic i Provincial de Barcelona

Barcelona, Spain, 08036

Status
Completed
 

Trial Design