A randomized, open label, multicenter Phase 2/3 study to evaluate the efficacy and safety of rogaratinib (BAY 1163877) compared to chemotherapy in patients with FGFR-positive locally advanced or metastatic urothelial carcinoma who have received prior platinum-containing chemotherapy
- Conditions
- bladder cancerurothelial carcinoma10004994
- Registration Number
- NL-OMON46559
- Lead Sponsor
- Bayer
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 41
- Existence of archival or fresh biopsy for FGFR testing
- FGFR testing of patients will be performed at the investigators* discretion up to a max. of 90 days prior to start of screening. Investigators should ensure all patients will be eligible in terms of disease status and lines of treatment within this timeframe.
- Documented urothelial carcinoma (transitional cell carcinoma) including urinary bladder, renal pelvis, ureters, urethra meeting all of the following criteria
-- Histologically or cytologically confirmed (patients with mixed histologies are required to have a dominant transitional cell pattern.)
-- Locally advanced (T4b, any N; or any T, N 2*3) or metastatic disease (any T, any N and M1). Locally advanced bladder cancer must be unresectable i.e. invading the pelvic or abdominal wall (stage T4b) or presenting with bulky nodal disease (N2-3).
- ECOG (Eastern Cooperative Oncology Group) Performance Status of 0 or 1
- Disease progression during or following treatment with at least one platinum-containing regimen (patients should have been treated for at least 2 cycles). In patients who received prior adjuvant/neoadjuvant platinum-containing chemotherapy, progression had to occur within 12
months of treatment.
- High FGFR1 or 3 mRNA (Messenger ribonucleic acid) expression levels (RNAscope score of 3+ or 4+; measurement is part of this protocol) in archival or fresh Tumor biopsy specimen
- At least 1 measurable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST v.1.1) in contrast enhanced (unless contraindicated) CT or MRI
- Previous or concurrent cancer except
-- cervical carcinoma in situ
-- treated basal-cell or squamous cell skin carcinoma
-- any cancer curatively treated > 3 years before randomization
-- Curatively treated incidental prostate cancer (T1/T2a)
- Ongoing or previous anti-cancer treatment within 4 weeks before randomization.
- More than two prior lines of systemic anti-cancer therapy for urothelial carcinoma
- Ongoing or previous treatment with anti-FGFR directed therapies (e.g. receptor tyrosine kinase inhibitors including rogaratinib or FGFRspecific antibodies) or with taxanes or vinflunine
- Unresolved toxicity higher than National Cancer Institute*s Common Terminology Criteria for Adverse Events, version 4.03 (CTCAE v.4.03) Grade 1 attributed to any prior therapy/procedure excluding alopecia, anemia and/or hypothyroidism
- History or current condition of an uncontrolled cardiovascular disease including any of the following conditions:
-- Congestive heart failure (CHF) NYHA (New York Heart Association) > Class 2
-- Unstable angina (symptoms of angina at rest) or new-onset angina (within last 3 months before randomization)
-- Myocardial infarction (MI) within past 6 months beforerandomization
-- Unstable cardiac arrhythmias requiring anti-arrhythmic therapy. Patients with arrhythmia under control with anti-arrhythmic therapy such as beta-blockers or digoxin are eligible.
- Arterial or venous thrombotic events or embolic events such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis or pulmonary embolism within 3 months before randomization
- Current evidence of endocrine alteration of calcium Phosphate homeostasis (e.g. parathyroid disorder, history of parathyroidectomy, tumor lysis, tumoral calcinosis, paraneoplastic hypercalcemia)
- Any hemorrhage / bleeding event * CTCAE v.4.03 Grade 3 within 4 weeks before randomization
- Current diagnosis of any retinal detachment, retinal pigment epithelial detachment (RPED), serous retinopathy or retinal vein occlusion
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>The primary endpoints are overall survival.</p><br>
- Secondary Outcome Measures
Name Time Method <p>The secondary endpoints are Progression-free survival, Objective response rate,<br /><br>Disease-control rate, Duration of response and Incidence of Adverse Events as a<br /><br>measure of safety and tolerability.</p><br>