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Study of Rogaratinib (BAY1163877) vs Chemotherapy in Patients With FGFR (Fibroblast Growth Factor Receptor)-Positive Locally Advanced or Metastatic Urothelial Carcinoma (FORT-1)

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ClinicalTrials.gov Identifier: NCT03410693
Recruitment Status : Active, not recruiting
First Posted : January 25, 2018
Last Update Posted : July 22, 2019
Sponsor:
Information provided by (Responsible Party):
Bayer

Tracking Information
First Submitted Date  ICMJE January 19, 2018
First Posted Date  ICMJE January 25, 2018
Last Update Posted Date July 22, 2019
Actual Study Start Date  ICMJE May 31, 2018
Estimated Primary Completion Date April 25, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 19, 2018)
Overall Survival [ Time Frame: Up to 45 months ]
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03410693 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: January 19, 2018)
  • Progression-free survival (PFS) [ Time Frame: Up to 45 months ]
    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.
  • Objective response rate (ORR) [ Time Frame: Up to 45 months ]
    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.
  • Disease-control rate (DCR) [ Time Frame: Up to 45 months ]
    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.
  • Duration of response (DOR) [ Time Frame: Up to 45 months ]
    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.
  • Incidence of Adverse Events as a measure of safety and tolerability [ Time Frame: Up to 45 months ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of Rogaratinib (BAY1163877) vs Chemotherapy in Patients With FGFR (Fibroblast Growth Factor Receptor)-Positive Locally Advanced or Metastatic Urothelial Carcinoma
Official Title  ICMJE 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
Brief 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 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.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Carcinoma, Transitional Cell
Intervention  ICMJE
  • Drug: Rogaratinib (BAY1163877)
    Rogaratinib administered as oral (p.o.) tablets twice daily (b.i.d.) continuously
  • Drug: Chemotherapy
    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, taking into consideration the status of the authorization in the given Country (i.e. the drug has to be approved at least for one indication in the given country).
Study Arms  ICMJE
  • Experimental: Rogaratinib

    Rogaratinib 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. 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".
    Intervention: Drug: Rogaratinib (BAY1163877)
  • Active Comparator: Chemotherapy

    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. 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".
    Intervention: Drug: Chemotherapy
Publications * Grünewald S, Politz O, Bender S, Héroult M, Lustig K, Thuss U, Kneip C, Kopitz C, Zopf D, Collin MP, Boemer U, Ince S, Ellinghaus P, Mumberg D, Hess-Stumpp H, Ziegelbauer K. Rogaratinib: A potent and selective pan-FGFR inhibitor with broad antitumor activity in FGFR-overexpressing preclinical cancer models. Int J Cancer. 2019 Feb 26. doi: 10.1002/ijc.32224. [Epub ahead of print]

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: March 14, 2019)
175
Original Estimated Enrollment  ICMJE
 (submitted: January 19, 2018)
400
Estimated Study Completion Date  ICMJE April 25, 2022
Estimated Primary Completion Date April 25, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia,   Austria,   Belgium,   Canada,   China,   Czechia,   Denmark,   Finland,   France,   Germany,   Hong Kong,   Hungary,   Ireland,   Israel,   Italy,   Japan,   Korea, Republic of,   Netherlands,   Poland,   Portugal,   Russian Federation,   Singapore,   Slovakia,   Spain,   Sweden,   Switzerland,   Taiwan,   United Kingdom,   United States
Removed Location Countries Brazil
 
Administrative Information
NCT Number  ICMJE NCT03410693
Other Study ID Numbers  ICMJE 17403
2016-004340-11 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Bayer
Study Sponsor  ICMJE Bayer
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Bayer Study Director Bayer
PRS Account Bayer
Verification Date July 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP