Description:
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 FGFR-positive
locally advanced or metastatic urothelial carcinoma who have received prior
platinum-containing chemotherapy.
The primary objective is to demonstrate the superiority of rogaratinib over chemotherapy in
terms of objective response rate (before: overall survivial) of urothelial carcinoma patients
with FGFR positive tumors.
At randomization, patients will have locally advanced or metastatic urothelial carcinoma and
have received at least one prior platinum-containing 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.
Related Conditions:
- Bladder Urothelial Carcinoma
- Infiltrating Renal Pelvis and Ureter Urothelial Carcinoma
- Renal Pelvis Urothelial Carcinoma
- Transitional Cell Carcinoma
- Ureter Urothelial Carcinoma
- Urethral Urothelial Carcinoma
- Urothelial Carcinoma
Title
- Brief Title: Study of Rogaratinib (BAY1163877) vs Chemotherapy in Patients With FGFR (Fibroblast Growth Factor Receptor)-Positive Locally Advanced or Metastatic Urothelial Carcinoma
- Official Title: A Randomized, Open Label, Multicenter Phase 2/3 Study to Evaluate the Efficacy and Safety of Rogaratinib (BAY1163877) Compared to Chemotherapy in Patients With FGFR-positive Locally Advanced or Metastatic Urothelial Carcinoma Who Have Received Prior Platinum-containing Chemotherapy
Clinical Trial IDs
- ORG STUDY ID:
17403
- SECONDARY ID:
2016-004340-11
- NCT ID:
NCT03410693
Conditions
- Carcinoma, Transitional Cell
Interventions
Drug | Synonyms | Arms |
---|
Rogaratinib (BAY1163877) | | Rogaratinib |
Chemotherapy | | Chemotherapy |
Purpose
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
platinum-containing chemotherapy.
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.
At randomization, patients will have locally advanced or metastatic urothelial carcinoma and
have received at least one prior platinum-containing 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.
Trial Arms
Name | Type | Description | Interventions |
---|
Rogaratinib | Experimental | Rogaratinib treatment study arm, comprising
Pre-treatment period, including FGFR testing and screening,
Treatment period, and
Follow-up period, including active follow-up and long-term follow-up. Patients will be considered "on study" during the pre-treatment, treatment and active followup periods. During the long-term follow-up period the patients will be considered "off study". | |
Chemotherapy | Active Comparator | Chemotherapy treatment study arm, comprising
Pre-treatment period, including FGFR testing and screening,
Treatment period, and
Follow-up period, including active follow-up and long-term follow-up. Patients will be considered "on study" during the pre-treatment, treatment and active followup periods. During the long-term follow-up period the patients will be considered "off study". | |
Eligibility Criteria
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 before randomization
- 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
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Overall Survival |
Time Frame: | Up to 45 months |
Safety Issue: | |
Description: | Defined as the time (days) from randomization to death due to any cause. Patients alive at the date of data cut-off for analysis will be censored at the last date known to be alive. |
Secondary Outcome Measures
Measure: | Progression-free survival (PFS) |
Time Frame: | Up to 45 months |
Safety Issue: | |
Description: | Defined as the time (days) from randomization to date of first observed disease progression (radiological or clinical assessment) or death due to any cause, if death occurs before progression is documented. For patients without documented radiological or clinical progression or death at the time of analysis, PFS will be censored at the last actual visit date of tumor evaluation. |
Measure: | Objective response rate (ORR) |
Time Frame: | Up to 45 months |
Safety Issue: | |
Description: | Defined as the percentage of patients with complete response (CR) or partial Response (PR). Patients for whom overall best response is not CR or PR, as well as patients without any post-baseline tumor assessment will be considered non-responders. |
Measure: | Disease-control rate (DCR) |
Time Frame: | Up to 45 months |
Safety Issue: | |
Description: | Defined as the percentage of patients, whose overall best response was not progressive disease [PD] (i.e. CR, PR, Stable Disease [SD] or Non CR/Non PD). Tumor assessments with SD as response, that is performed prematurely after randomization of the patient (i.e. substantially earlier than the first planned radiological tumor assessment at 6 weeks), will not be taken into account. |
Measure: | Duration of response (DOR) |
Time Frame: | Up to 45 months |
Safety Issue: | |
Description: | Defined as the time from the first documented objective response of PR or CR, whichever is noted earlier, to disease progression or death (if death occurs before progression is documented). DOR will be defined for responders only, i.e. patients with a CR or PR. |
Measure: | Incidence of Adverse Events as a measure of safety and tolerability |
Time Frame: | Up to 45 months |
Safety Issue: | |
Description: | |
Details
Phase: | Phase 2/Phase 3 |
Primary Purpose: | Interventional |
Overall Status: | Not yet recruiting |
Lead Sponsor: | Bayer |
Trial Keywords
Last Updated
April 13, 2018