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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 : Completed
First Posted : January 25, 2018
Results First Posted : December 29, 2021
Last Update Posted : September 28, 2022
Sponsor:
Information provided by (Responsible Party):
Bayer

Study Description
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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 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.


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

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 175 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
Actual Primary Completion Date : October 27, 2020
Actual Study Completion Date : October 27, 2020

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Arms and Interventions
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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 or treatment guidelines in the given country.


Outcome Measures
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Primary Outcome Measures :
  1. Objective Response Rate (ORR) - Central Assessment [ Time Frame: From start of treatment up to end of active follow-up, approximately 29 months ]
    ORR is defined as the percentage of participants with complete response (CR) or partial response (PR). participants for whom overall best response is not CR or PR, as well as participants without any post-baseline tumor assessment will be considered non-responders.


Secondary Outcome Measures :
  1. Disease-control Rate (DCR) - Central Assessment [ Time Frame: From start of treatment till end of active follow-up, approximately 29 months ]
    DCR was defined as the percentage of participants whose overall best response was not a progressive disease (i.e., CR, PR, stable disease [SD] or Non CR/Non PD).

  2. Progression-free Survival (PFS) - Central Assessment [ Time Frame: From start of treatment till end of active follow-up, approximately 29 months ]
    Progression free survival (PFS) was defined as the time (days) from randomization to date of first observed disease progression (radiological or clinical assessment or both) or death due to any cause (if death occurred before progression was documented).

  3. Duration of Response (DOR) - Central Assessment [ Time Frame: From start of treatment till end of active follow-up, approximately 29 months ]
    DOR (for patients with PR and CR only) was defined as the time from the first documented objective response of PR or CR, whichever was noted earlier, to disease progression (including symptomatic deterioration) or death, whichever was earlier

  4. Number of Participants With Treatment Emergent Adverse Events [ Time Frame: From start of treatment up to 30 days after the last administration of study treatment, approximately 29 months ]
    A treatment-emergent event was defined as any event arising or worsening after the start of study drug administration until 30 days after the last administration of study treatment


Eligibility Criteria
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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. Mandatory FGFR testing of patients will be performed prior to start of screening. The timing of the FGFR test is at the discretion of the investigator. Investigators should ensure all patients will be eligible in terms of disease status and lines of treatment.

  • Documented urothelial carcinoma (transitional cell carcinoma) including urinary bladder, renal pelvis, ureters, urethra meeting all of the following criteria

    • Histologically confirmed (Patients with mixed histologies are required to have a dominant transitional cell pattern.)
    • Locally advanced (T4, 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 expression levels in archival or fresh tumor biopsy specimen quantified as outlined in the lab manual
  • 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 treatment with anti-FGFR directed therapies (e.g. receptor tyrosine kinase inhibitors including rogaratinib or FGFR-specific antibodies) or with taxanes or vinflunine
  • More than two prior lines of systemic anti-cancer therapy for urothelial carcinoma given for advanced unresectable/ metastatic disease
  • Ongoing or previous anti-cancer treatment within 4 weeks before randomization.
  • 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)
  • Current diagnosis of any retinal detachment, retinal pigment epithelial detachment (RPED), serous retinopathy or retinal vein occlusion
  • Any hemorrhage / bleeding event ≥ CTCAE v.4.03 Grade 3 within 4 weeks before randomization
Contacts and Locations
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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


Locations
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Sponsors and Collaborators
Bayer
Investigators
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Study Director: Bayer Study Director Bayer
  Study Documents (Full-Text)

Documents provided by Bayer:
Study Protocol  [PDF] November 19, 2019
Statistical Analysis Plan  [PDF] August 19, 2020

More Information
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Additional Information:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: Bayer
ClinicalTrials.gov Identifier: NCT03410693    
Other Study ID Numbers: 17403
2016-004340-11 ( EudraCT Number )
First Posted: January 25, 2018    Key Record Dates
Results First Posted: December 29, 2021
Last Update Posted: September 28, 2022
Last Verified: September 2022

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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:
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Carcinoma
Carcinoma, Transitional Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms