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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 : Recruiting
First Posted : January 25, 2018
Last Update Posted : November 20, 2018
Sponsor:
Information provided by (Responsible Party):
Bayer

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.


Condition or disease Intervention/treatment Phase
Carcinoma, Transitional Cell Drug: Rogaratinib (BAY1163877) Drug: Chemotherapy Phase 2 Phase 3

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 400 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : May 31, 2018
Estimated Primary Completion Date : April 25, 2022
Estimated Study Completion Date : April 25, 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
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".
Drug: Rogaratinib (BAY1163877)
Rogaratinib administered as oral (p.o.) tablets twice daily (b.i.d.) continuously

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".
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).




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. Incidence of Adverse Events as a measure of safety and tolerability [ Time Frame: Up to 45 months ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03410693


Contacts
Contact: Bayer Clinical Trials Contact (+) 1-888-8422937 clinical-trials-contact@bayer.com

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Sponsors and Collaborators
Bayer
Investigators
Study Director: Bayer Study Director Bayer

Additional Information:
Responsible Party: Bayer
ClinicalTrials.gov Identifier: NCT03410693     History of Changes
Other Study ID Numbers: 17403
2016-004340-11 ( EudraCT Number )
First Posted: January 25, 2018    Key Record Dates
Last Update Posted: November 20, 2018
Last Verified: November 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Bayer:
Urothelial carcinoma

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Transitional Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms