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 Outcome 1 - Measure: Number of subjects with Dose-limiting toxicities(DLTs) in Part A
Primary Outcome 1 - Time Frame: Up to 21 days
Primary Outcome 2 - Measure: Number of subjects with treatment-emergent adverse events (TEAEs) in Part A
Primary Outcome 2 - Time Frame: Up to 5 months
Primary Outcome 3 - Measure: Number of subjects with drug-related TEAEs in Part A
Primary Outcome 3 - Time Frame: Up to 5 months
Primary Outcome 4 - Measure: Number of subjects with treatment-emergent serious adverse events(TESAEs) in Part A
Primary Outcome 4 - Time Frame: Up to 5 months
Primary Outcome 5 - Measure: Progression Free Survival(PFS)
Primary Outcome 5 - Time Frame: Up to 25 months
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 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.
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Gender: All
Minimum Age: 18 Years
Maximum Age: N/A
Healthy Volunteers: No
Name: Bayer Clinical Trials Contact
Phone: (+) 1-888-8422937
Email: clinical-trials-contact@bayer.com
Facility | Status | Contact |
---|---|---|
University of Arizona Cancer Center Tucson, Arizona 85724 United States |
Recruiting | |
University of California - Davis Sacramento, California 95817 United States |
Withdrawn | |
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 |
Recruiting | |
Ordensklinikum Linz GmbH Elisabethinen Linz, Oberösterreich 4020 Austria |
Recruiting | |
Uniklinikum Salzburg - Landeskrankenhaus Salzburg, 5020 Austria |
Recruiting | |
Krankenhaus der Barmherzigen Brüder Wien, 1020 Austria |
Recruiting | |
Universitätsklinikum AKH Wien Wien, 1090 Austria |
Recruiting | |
Institut Bergonié - Unicancer Nouvelle Aquitaine Bordeaux Cedex, 33076 France |
Recruiting | |
Centre Oscar Lambret - Lille Lille Cedex, 59020 France |
Recruiting | |
Institut de Cancérologie de l'Ouest - Saint Herblain Nantes, 44805 France |
Recruiting | |
Eberhard-Karls-Universität Tübingen Tübingen, Baden-Württemberg 72076 Germany |
Not yet recruiting | |
Universitätsklinikum Essen Essen, Nordrhein-Westfalen 45122 Germany |
Recruiting | |
Universitätsklinikum Köln Köln, Nordrhein-Westfalen 50937 Germany |
Recruiting | |
Universitätsmedizin der Johannes Gutenberg Universität Mainz Mainz, Rheinland-Pfalz 55131 Germany |
Recruiting | |
A.O.U. di Modena - Policlinico Modena, Emilia-Romagna 41124 Italy |
Completed | |
Fondazione IRCCS Istituto Nazionale dei Tumori Milano, Lombardia 20133 Italy |
Recruiting | |
IRCCS Istituto Europeo di Oncologia (IEO) Milano, Lombardia 20141 Italy |
Recruiting | |
IRCCS Istituto Oncologico Veneto (IOV) Padova, Veneto 35128 Italy |
Recruiting | |
A.O.U.I. Verona Verona, Veneto 37134 Italy |
Recruiting | |
National Cancer Center Hospital East Kashiwa, Chiba 277-8577 Japan |
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, 26426 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 |