Clinical Trials /

Study of Rogaratinib (BAY1163877) vs Chemotherapy in Patients With FGFR (Fibroblast Growth Factor Receptor)-Positive Locally Advanced or Metastatic Urothelial Carcinoma

NCT03410693

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 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.

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
Recruiting Status:

Active, not recruiting

Phase:

Phase 2/Phase 3

Trial Eligibility

Document

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

DrugSynonymsArms
Rogaratinib (BAY1163877)Rogaratinib
ChemotherapyChemotherapy

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

NameTypeDescriptionInterventions
RogaratinibExperimentalRogaratinib 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".
  • Rogaratinib (BAY1163877)
ChemotherapyActive ComparatorChemotherapy 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

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

  • Urothelial carcinoma

Last Updated

April 13, 2018