Clinical Trials /

A Study of E7090 in Participants With Unresectable Advanced or Metastatic Cholangiocarcinoma With Fibroblast Growth Factor Receptor (FGFR) 2 Gene Fusion

NCT04238715

Description:

The primary purpose of the study is to assess the objective response rate (ORR) of E7090 by Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 based on independent imaging review (IIR) in participants with unresectable cholangiocarcinoma with FGFR2 gene fusion who failed gemcitabine-based combination chemotherapy.

Related Conditions:
  • Intrahepatic Cholangiocarcinoma
  • Perihilar Intrahepatic Cholangiocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Study of E7090 in Participants With Unresectable Advanced or Metastatic Cholangiocarcinoma With Fibroblast Growth Factor Receptor (FGFR) 2 Gene Fusion
  • Official Title: A Multicenter, Open-Label, Phase 2 Trial of E7090 in Subjects With Unresectable Advanced or Metastatic Cholangiocarcinoma With Fibroblast Growth Factor Receptor (FGFR) 2 Gene Fusion

Clinical Trial IDs

  • ORG STUDY ID: E7090-J000-201
  • NCT ID: NCT04238715

Conditions

  • Cholangiocarcinoma

Interventions

DrugSynonymsArms
E7090E7090 140 mg

Purpose

The primary purpose of the study is to assess the objective response rate (ORR) of E7090 by Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 based on independent imaging review (IIR) in participants with unresectable cholangiocarcinoma with FGFR2 gene fusion who failed gemcitabine-based combination chemotherapy.

Trial Arms

NameTypeDescriptionInterventions
E7090 140 mgExperimentalParticipants will receive E7090 140 mg (milligram), tablets orally once daily (QD), in 28-days treatment cycle until disease progression, development of unacceptable toxicity, participant requests to discontinue, withdrawal of consent or study termination.
  • E7090

Eligibility Criteria

        Inclusion Criteria:

          1. Participants with a histologically or cytologically diagnosis of intrahepatic or
             perihilar cholangiocarcinoma who agree to provide archival tumor sample or residual
             biopsy sample, or agree with tumor biopsy

          2. Participants who have confirmed FGFR2 gene fusion of tumor by fluorescence in situ
             hybridization (FISH) in central laboratory. FGFR2 gene fusion confirmed by the same
             FISH assay in another test/study will be discussed with the sponsor and agreed on a
             case by case basis

          3. Participants with surgically unresectable or advanced/metastatic disease who have
             received at least one prior chemotherapy including gemcitabine-based combination
             chemotherapy (example: gemcitabine and cisplatin)

          4. Measurable disease meeting the following criteria:

               1. At least 1 lesion of >=1.0 centimeter (cm) in the longest diameter for a
                  non-lymph node or >=1.5 cm in the short-axis diameter for a lymph node that is
                  serially measurable according to RECIST 1.1 using computerized
                  tomography/magnetic resonance imaging (CT/MRI).

               2. Lesions that have had external beam radiotherapy (EBRT) or locoregional therapies
                  such as radiofrequency (RF) ablation must show evidence of progressive disease
                  based on RECIST 1.1 to be deemed a target lesion.

          5. Corrected serum calcium less than or equal to (<=) upper limit of normal (ULN)

          6. Phosphate <=ULN

          7. Participants with Performance Status (PS) score of 0-1 established by Eastern
             Cooperative Oncology Group (ECOG)

          8. Participants who are expected to survive for 3 months or longer after starting
             administration of the investigational drug

          9. Washout period required from the end of prior treatment to the start of E7090
             administration will be as follows

               1. Antibody and other investigational drugs : >=4 weeks

               2. Prior chemotherapy (except small-molecule targeted therapy), surgical therapy,
                  radiation therapy:>=3 weeks

               3. Endocrine therapy, immunotherapy, small-molecule targeted therapy: >=2 weeks

        Exclusion Criteria:

          1. Participants with brain or subdural metastases are not eligible, unless they have
             completed local therapy and have discontinued the use of corticosteroids for this
             indication for at least 4 weeks before starting treatment in this study. Any signs
             (example: radiologic) or symptoms of brain metastases must be stable for at least 4
             weeks before starting study treatment.

          2. Concomitant active infection requiring systemic treatment (except hepatitis B or C
             virus-infected participants who are under anti-viral treatment)

          3. Participants who test positive for human immunodeficiency virus (HIV antibody) at
             Screening 2

          4. Child-Pugh score B or C

          5. Moderate or severe ascites extending from the pelvis to the liver surface

          6. Following ocular disorders.

               1. Current evidence of Grade 2 or higher corneal disorder

               2. Current evidence of active macula disorder (example: age-related macular
                  degeneration, central serous chorioretinal disease)

          7. Participants whose toxicity of previous treatment has not recovered to Grade 1 or
             lower per Common Terminology Criteria for Adverse Events (CTCAE v4.03), except for
             alopecia, infertility and the adverse events listed in inclusion criteria.

          8. Participants with prior therapy targeting FGFR2.

          9. Participants who need the use of drugs or foods that strongly inhibits or induces the
             metabolizing enzyme cytochrome P450 (CYP) 3A4.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:20 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:ORR
Time Frame:From first dose of study drug until disease progression, development of unacceptable toxicity, participant requests to discontinue, withdrawal of consent or study termination (up to approximately 2.3 years)
Safety Issue:
Description:The ORR will be assessed by IIR based on RECIST version 1.1. ORR is defined as a percentage of participants with best overall response (BOR) of complete response (CR) or partial response (PR). CR: disappearance of all lesions. PR: For PR, longest diameter will be used for non-lymph target lesions but short axis is measured for lymph lesions. PR: greater than or equal to (>=) 30 percent (%) decrease in sum of diameters of target lesions taking as reference baseline, associated to non-progressive disease (non-PD) response for non-target (NT) lesions.

Secondary Outcome Measures

Measure:Progression Free Survival (PFS)
Time Frame:From the date of first dose to the date of first documentation of disease progression or date of death from any cause, whichever occurs first (up to approximately 2.3 years)
Safety Issue:
Description:PFS will be assessed by IIR based on RECIST version 1.1. PFS is defined as the time from the date of first dose to the date of first documentation of disease progression or date of death from any cause, whichever occurs first.
Measure:Duration of Response (DOR)
Time Frame:From the date of first documentation of CR or PR to the date of first documentation of disease progression or date of death from any cause, whichever occurs first (up to approximately 2.3 years)
Safety Issue:
Description:DOR will be assessed by IIR based on RECIST version 1.1. DOR is defined as the time from the date of first documentation of CR or PR to the date of first documentation of disease progression or date of death from any cause, whichever occurs first. CR: disappearance of all lesions. PR: For PR, longest diameter will be used for non-lymph target lesions but short axis is measured for lymph lesions. PR: greater than or equal to >=30% decrease in sum of diameters of target lesions taking as reference baseline, associated to non-PD response for NT lesions.
Measure:Time to Response (TTR)
Time Frame:from the date of first study dose to the date of first documentation of CR or PR (up to approximately 2.3 years)
Safety Issue:
Description:TTR will be assessed by IIR based on RECIST version 1.1. TTR is defined as the time from the date of first study dose to the date of first documentation of CR or PR. CR: disappearance of all lesions. PR: For PR, longest diameter will be used for non-lymph target lesions but short axis is measured for lymph lesions. PR: greater than or equal to >=30% decrease in sum of diameters of target lesions taking as reference baseline, associated to non-PD response for NT lesions.
Measure:Overall Survival (OS)
Time Frame:From the date of first dose to the date of death from any cause (up to approximately 2.3 years)
Safety Issue:
Description:OS is defined as the time from the date of first dose to the date of death from any cause. For the participants who are alive or unknown, OS is censored as the date of last known alive date.
Measure:Disease Control Rate (DCR)
Time Frame:From first dose of study drug until disease progression, development of unacceptable toxicity, participant requests to discontinue, withdrawal of consent or study termination (up to approximately 2.3 years)
Safety Issue:
Description:DCR will be assessed by IIR based on RECIST version 1.1. DCR is defined as a percentage of participants with BOR of CR, PR or stable disease (SD). The BOR of SD has to be observed greater than or equal to (>=) 7 weeks from the date of first study dose. CR: disappearance of all lesions. PR: For PR, longest diameter will be used for non-lymph target lesions but short axis is measured for lymph lesions. PR: greater than or equal to >=30% decrease in sum of diameters of target lesions taking as reference baseline, associated to non-PD response for NT lesions.
Measure:Clinical Benefit Rate (CBR)
Time Frame:From first dose of study drug until disease progression, development of unacceptable toxicity, participant requests to discontinue, withdrawal of consent or study termination (up to approximately 2.3 years)
Safety Issue:
Description:CBR will be assessed by IIR based on RECIST version 1.1. CBR is defined as a percentage of participants with BOR of CR, PR or durable SD (dSD) (duration of SD >=23 weeks). CR: disappearance of all lesions. PR: For PR, longest diameter will be used for non-lymph target lesions but short axis is measured for lymph lesions. PR: greater than or equal to >=30% decrease in sum of diameters of target lesions taking as reference baseline, associated to non-PD response for NT lesions.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Eisai Co., Ltd.

Trial Keywords

  • E7090
  • Cholangiocarcinoma
  • Unresectable cholangiocarcinoma
  • Metastatic cholangiocarcinoma
  • Fibroblast Growth Factor Receptor 2 (FGFR2)
  • FGFR2 gene fusion

Last Updated

January 24, 2020