The primary objective of the entire study is to compare rogaratinib (BAY1163877) with chemotherapy (docetaxel, paclitaxel or vinflunine) in terms of prolonging the Overall survival (OS) of patients with FGFR positive urothelial carcinoma.
ID
Source
Brief title
Condition
- Bladder and bladder neck disorders (excl calculi)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary endpoints are overall survival.
Secondary outcome
The secondary endpoints are Progression-free survival, Objective response rate,
Disease-control rate, Duration of response and Incidence of Adverse Events as a
measure of safety and tolerability.
Background summary
This is 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 FGFRpositive locally advanced or metastatic
urothelial carcinoma who have received Prior platinumcontaining
chemotherapy. At randomization, patients will have locally advanced or
metastatic urothelial carcinoma and have received at least one prior
platinumcontaining chemotherapy regimen. Only patients with FGFR1 or 3 positive
tumors can be randomized into the study. Archival tumor tissue is adequate for
testing of FGFR1 and 3 mRNA expressions, which will be determined centrally
using an RNA in situ hybridization (RNA-ISH) test. Approximately 42 % of UC
patients with locally advanced or metastatic UC are identified as FGFR-positive
by the RNA-ISH cut-off applied.
Study objective
The primary objective of the entire study is to compare rogaratinib
(BAY1163877) with chemotherapy (docetaxel, paclitaxel or vinflunine) in terms
of prolonging the Overall survival (OS) of patients with FGFR positive
urothelial carcinoma.
Study design
A randomized, open label, multicenter Phase 2/3 study. Patients will be
randomly assigned in a 1:1 ration rogaratinib (BAY 1163877) or standard of care
chemotherapy.
Intervention
Rogaratinib administered as oral tablets twice daily continuously.
Rogaritinib treatment study arm, comprising:
1) Pre-treatment period, including FGFR testing and screening,
2) Treatment period, and
3) Follow-up period, including active follow-up and long-term follow-up.
Chemotherapy as taxane (docetaxel or paclitaxel) or vinflunine administered
through intravenous (i.v.) infusion every 3 weeks (on day 1 of a 21-day cycle).
The choice of the chemotherapy is at the discretion of the investigator.
Chemotherapy treatment study arm, comprising:
1) Pre-treatment period, including FGFR testing and screening,
2) Treatment period, and
3) Follow-up period, including active follow-up and long-term follow-up.
Study burden and risks
Rogaratinib may have a therapeutic benefit, but this can*t be guaranteed.
Patients are at risk of side effects.
Each patient will undergo a pre-screening visit for testing FGFR
over-expression; in some cases, a new biopsy
should be obtained for this purpose.
Blood tests for and after each study medication administration for: ensuring
the safety and pharmacokinetic- and
biomarker analyzes.
Radiation exposure: Radiological tumor assessment takes place during screening
every six weeks during the first four months and then
every 9 weeks until disease progression. A bonescan is made at screening visit.
Eye examination in specific study visits.
ECG at specific study visits.
Collection of urine at specific study visits.
A questionnaire on specific study visit.
Physical examination in specific study visits.
If the patient stops the study medication for another reason, a phase of active
follow-up with a number of study visits
the same as those of the radiological examinations will follow. If the patient
stop taking the study medication for
disease progression, a phase of long-term follow-up by telephone will follow.
Energieweg 1
Mijdrecht 3641 RT
NL
Energieweg 1
Mijdrecht 3641 RT
NL
Listed location countries
Age
Inclusion criteria
- 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
Exclusion criteria
- 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
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2016-004340-11-NL |
| CCMO | NL62741.031.17 |