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BRIEF TITLE: 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

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


  • Org Study ID: 19131
  • Secondary ID: 2017-001483-38
  • NCT ID: NCT03473756
  • NCT Alias:
  • Sponsor: Bayer - Industry
  • Source: 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.

Overal Status Start Date Phase Study Type
Recruiting May 15, 2018 Phase 1/Phase 2 Interventional

Primary Outcomes:

Primary Outcome 1 - Measure: Progression Free Survival(PFS)

Primary Outcome 1 - Time Frame: Up to 25 months

Primary Outcome 2 - Measure: Number of subjects with Dose-limiting toxicities(DLTs) in Part A

Primary Outcome 2 - Time Frame: Up to 21 days

Primary Outcome 3 - Measure: Number of subjects with treatment-emergent adverse events (TEAEs) in Part A

Primary Outcome 3 - Time Frame: Up to 5 months

Primary Outcome 4 - Measure: Number of subjects with drug-related TEAEs in Part A

Primary Outcome 4 - Time Frame: Up to 5 months

Primary Outcome 5 - Measure: Number of subjects with treatment-emergent serious adverse events(TESAEs) in Part A

Primary Outcome 5 - Time Frame: Up to 5 months

Condition:

  • Urothelial Carcinoma

Eligibility

Criteria:
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.

- 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

- Hearing loss (measured by audiometry) of 25 dB at two contiguous frequencies

- 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.
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Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No

Overall Contact

Name: Bayer Clinical Trials Contact

Phone: (+) 1-888-8422937

Email: clinical-trials-contact@bayer.com

Locations

Facility Status Contact
University of Arizona Cancer Center
Tucson, Arizona 85724
United States
Recruiting
University of California - Davis
Sacramento, California 95817
United States
Not yet recruiting
Comprehensive Cancer Center
Chicago, Illinois 60637
United States
Recruiting
Barbara Ann Karmanos Cancer Institute
Detroit, Michigan 48201
United States
Recruiting
Memorial Sloan-Kettering Cancer Center
New York, New York 10065
United States
Not yet recruiting
Krankenhaus der Barmherzigen Schwestern Linz
Linz, Oberösterreich 4010
Austria
Recruiting
Uniklinikum Salzburg - Landeskrankenhaus
Salzburg, 5020
Austria
Recruiting
Krankenhaus der Barmherzigen Brüder
Wien, 1020
Austria
Recruiting
Allgemeines Krankenhaus der Stadt Wien
Wien, 1090
Austria
Recruiting
Institut Bergonié
Bordeaux Cedex, 33076
France
Recruiting
Centre Oscar Lambret - Lille
Lille Cedex, 59020
France
Recruiting
Centre René Gauducheau - Nantes
Nantes, 44805
France
Not yet recruiting
Eberhard-Karls-Universität Tübingen
Tübingen, Baden-Württemberg 72076
Germany
Not yet recruiting
Universitätsklinikum Essen
Essen, Nordrhein-Westfalen 45122
Germany
Not yet recruiting
Universitätsklinikum Köln
Köln, Nordrhein-Westfalen 50937
Germany
Not yet recruiting
Universitätsmedizin der Johannes Gutenberg Universität Mainz
Mainz, Rheinland-Pfalz 55131
Germany
Recruiting
A.O.U. di Modena - Policlinico
Modena, Emilia-Romagna 41124
Italy
Not yet recruiting
Fondazione IRCCS Istituto Nazionale dei Tumori
Milano, Lombardia 20133
Italy
Recruiting
IRCCS Istituto Europeo di Oncologia
Milano, Lombardia 20141
Italy
Recruiting
IRCCS Istituto Oncologico Veneto (IOV)
Padova, Veneto 35128
Italy
Not yet recruiting
Centro di Ricerche Cliniche dell'A.O.U.I. di Verona
Verona, Veneto 37134
Italy
Recruiting
National Cancer Center Hospital East
Kashiwa, Chiba 277-8577
Japan
Not yet recruiting
National Hospital Organization Shikoku Cancer Center
Matsuyama, Ehime 791-0280
Japan
Recruiting
University of Tsukuba Hospital
Tsukuba, Ibaraki 305-8576
Japan
Recruiting
The Cancer Institute Hospital of JFCR
Koto-ku, Tokyo 135-8550
Japan
Recruiting
Asan Medical Center
Seoul, 05505
Korea, Republic of
Recruiting
Samsung Medical Center
Seoul, 06351
Korea, Republic of
Recruiting
Yonsei University College of Medicine
Seoul, 120-752
Korea, Republic of
Recruiting
Ciutat Sanitària i Universitaria de la Vall d'Hebron
Barcelona, 08035
Spain
Recruiting
Hospital Clínic i Provincial de Barcelona
Barcelona, 08036
Spain
Recruiting
Hospital de la Santa Creu i de Sant Pau
Barcelona, 08041
Spain
Not yet recruiting
Hospital Ramón y Cajal
Madrid, 28034
Spain
Recruiting
Hospital General Universitario de Valencia
Valencia, 46014
Spain
Recruiting