Clinical Trials /

NCCH2006/MK010 Trial (FORTUNE Trial)

NCT04962867

Description:

This is a single-arm, open-label, multicenter, investigator-initiated Phase 2 trial to evaluate the efficacy and safety of E7090 in patients with advanced or recurrent solid tumors harboring FGFR genetic alterations (including fusion, mutation, amplification).

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: NCCH2006/MK010 Trial (FORTUNE Trial)
  • Official Title: Multicenter Investigator-initiated Phase II Trial of E7090 in Patients With Advanced or Recurrent Solid Tumor With Fibroblast Growth Factor Receptor (FGFR) Gene Alteration (FORTUNE Trial)

Clinical Trial IDs

  • ORG STUDY ID: NCCH2006/MK010
  • NCT ID: NCT04962867

Conditions

  • Advanced or Recurrent Solid Tumors
  • FGFR Gene Alterations

Interventions

DrugSynonymsArms
E7090

Purpose

This is a single-arm, open-label, multicenter, investigator-initiated Phase 2 trial to evaluate the efficacy and safety of E7090 in patients with advanced or recurrent solid tumors harboring FGFR genetic alterations (including fusion, mutation, amplification).

Trial Arms

NameTypeDescriptionInterventions

Eligibility Criteria

        Inclusion Criteria:

          1. Participants with histologically or cytologically confirmed metastatic, unresectable,
             or recurrent solid tumor who agree to provide an archival tumor sample, a residual
             biopsy sample, or a fresh tumor biopsy sample

          2. Ineffective to or intolerant to initial treatment, or for which standard treatment is
             no longer available

          3. Participants with an FGFR gene alteration detected by NGS panel, who fall under one of
             the categories of groups A to C defined as below

             Group A: FGFR1-3 fusion

             Group B: FGFR1-3 specific activating mutations

             Group C: FGFR1-3 activating mutation not applicable to group B, or FGFR1, 2 gene
             amplification

          4. For Group D, participants with cholangiocarcinoma who have previously received a
             selective FGFR inhibitor other than E7090 and have demonstrated progressive disease or
             resistance

          5. Karnofsky Performance Status (KPS) >= 70 for patients with primary CNS tumors.
             Performance Status (ECOG) 0-1 for patients with non-primary CNS tumors

          6. For patients with non-primary CNS tumors, they have at least 1 lesion of >= 10
             millimeter (mm) in the longest diameter for a non-lymph node or >= 15 mm in the
             short-axis diameter for a lymph node that is considered as serially measurable
             according to RECIST v1.1 using computerized tomography or magnetic resonance imaging
             (CT or MRI) within 28 days of enrollment. However, lesions that have received local
             treatment such as external-beam radiation therapy (EBRT) or radiofrequency ablation
             (RFA) must have progressed after these local treatment to count as measurable lesion

          7. Participants with primary CNS tumors must meet all of the following criteria:

               1. Have received prior treatment including radiation and/or chemotherapy, as
                  recommended or appropriate for the CNS tumor type

               2. Have >= 1 site of bi-dimensionally measurable disease (confirmed by magnetic
                  resonance imaging (MRI) and evaluable by RANO criteria), with the size of at
                  least one of the measurable lesions >= 1 cm in each dimension and noted on more
                  than one imaging slice. Imaging study performed within 28 days before enrollment

               3. Must be neurologically stable based on neurologic exam at least for the last 7
                  days prior to enrollment. (based on medical examination/interview)

          8. Corrected calcium <= 10.1 mg/dL

          9. Phosphate <= 4.6 mg/dL

         10. Required treatment washout period, from the last day of prior treatment until
             enrollment of this trial, is as follows:

               1. Antibody and other investigational drugs: >= 28 days

               2. Prior chemotherapy (excluding small-molecule targeted therapy), surgical therapy,
                  radiation therapy: >= 21 days (>= 90 days from the date of the last radiation
                  therapy for primary CNS tumors)

               3. Endocrine therapy, immunotherapy, small-molecule targeted therapy: >=14 days

        Exclusion Criteria:

          1. Participants with brain, subdural or leptomeningeal metastases

          2. Participants with primary CNS tumor located in either cerebellum, brainstem, spinal
             cord, pituitary gland, optic nerve or olfactory nerve

          3. Positive for either human immunodeficiency virus (HIV) antibody, HBs antigen, or HCV
             antibody (patients with positive HCV antibody but no detectable HCV-RNA are not
             excluded)

          4. Negative for HBs antigen, but positive for HBs antibody or HBc antibody, and also
             positive for HBV-DNA quantification (not excluded if HBV-DNA is below detection
             sensitivity)

          5. Child-Pugh score B or C

          6. Participants with pericardial effusion, pleural effusion, or ascites requiring
             treatment

          7. Have any of the following ocular diseases

               1. Grade 2 or higher corneal disorders

               2. Active retinopathy (e.g., age-related macular degeneration, central serous
                  chorioretinal disease, retinal tear)

          8. Participants whose toxicity of previous treatment has not recovered to Grade 1 or
             lower per Common Terminology Criteria for Adverse Events (CTCAE v5.0), except for
             alopecia, infertility, and the laboratory test results listed in the inclusion
             criteria

          9. Participants who received a prior selective FGFR inhibitor in the recurrent/metastatic
             disease setting; except for patients with cholangiocarcinoma harboring FGFR2 fusion
             (Group D). Note that prior use of a multi-kinase inhibitor which includes anti-FGFR
             activity is acceptable after review by the lead investigator

         10. Participants who need the use of drugs that strongly inhibits or induces the
             metabolizing enzyme cytochrome P450 (CYP) 3A

         11. The presence of FGFR gatekeeper mutations as follows: FGFR1 V561, FGFR2 V564/565,
             FGFR3 V555/557, FGFR4 V550

         12. The presence of any of the following coexisting driver gene abnormalities:

               1. Genetic mutations (excluding VUS): KRAS, NRAS, EGFR, or BRAF V600

               2. Gene translocations: ALK, ROS1, or NTRK
      
Maximum Eligible Age:N/A
Minimum Eligible Age:20 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Objective response rate (ORR)
Time Frame:Baseline up to 3.5 years
Safety Issue:
Description:Overall response rate (ORR) defined as the combined incidence of complete response (CR) and PR, confirmed no less than 4 weeks after the criteria for response are first met, based on RECIST v1.1. ORR will be confirmed by independent blinded central review assessment.

Secondary Outcome Measures

Measure:Objective response rate (ORR)
Time Frame:Baseline up to 3.5 years
Safety Issue:
Description:Overall response rate (ORR) defined as the combined incidence of complete response (CR) and PR, confirmed no less than 4 weeks after the criteria for response are first met, based on Response Assessment in Neuro-Oncology (RANO) criteria for primary Central Nervous System (CNS) tumor or RECIST v1.1 for other tumor type. ORR will be confirmed by local site investigator and/or independent blinded central review assessment.
Measure:Progression-free survival (PFS)
Time Frame:Baseline up to 3.5 years
Safety Issue:
Description:Progression-free survival (PFS) defined as the time from the date of enrollment to the date of the first documentation of objective progression of disease (PD), clinically diagnosed symptomatic deterioration, or death due to any cause in the absence of documented PD, whichever occurs first.
Measure:Overall Survival (OS)
Time Frame:Baseline up to 3.5 years
Safety Issue:
Description:Overall survival (OS) defined as the time from date of enrollment to date of death due to any cause.
Measure:Disease control rate (DCR)
Time Frame:Baseline up to 3.5 years
Safety Issue:
Description:Disease control rate (DCR) defined as the percentage of patients with a confirmed complete response (CR), partial response (PR) or stable disease (SD) as the best overall according to RECIST version 1.1.
Measure:Adverse event (AE) rate
Time Frame:From the first dose of the investigational product until 30 days after the last dose of study drugs
Safety Issue:
Description:Defined as the percentage of patients who experienced each adverse event. The severity of AEs were evaluated by the investigator according to Japan Clinical Oncology Group (JCOG) Japanese translation of the Common Terminology Criteria for Adverse Events version 5.0 (CTCAE v5.0-JCOG).
Measure:Adverse reaction (adverse drug reaction) rate
Time Frame:From the first dose of the investigational product until 30 days after the last dose of study drugs
Safety Issue:
Description:Defined as the percentage of patients who experienced each adverse reaction (causally related to the protocol treatment). The severity of AEs were evaluated by the investigator according to Japan Clinical Oncology Group (JCOG) Japanese translation of the Common Terminology Criteria for Adverse Events version 5.0 (CTCAE v5.0-JCOG).
Measure:Duration of response (DOR)
Time Frame:Baseline up to 3.5 years
Safety Issue:
Description:Duration of Response (DOR) 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.
Measure:Time to response (TTR)
Time Frame:Baseline up to 3.5 years
Safety Issue:
Description:Time to response (TTR) defined as the time from the date of first study dose to the date of first documentation of CR or PR according to RECIST version 1.1.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:National Cancer Center, Japan

Trial Keywords

  • E7090
  • Solid tumor
  • Fibroblast Growth Factor Receptor (FGFR)
  • FGFR inhibitor

Last Updated

August 18, 2021