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)

National Cancer Center, Japan7 sites in 1 country75 target enrollmentJune 15, 2021

ConditionsAdvanced or Recurrent Solid Tumors FGFR Gene Alterations

DrugsE7090

Overview

Phase: Phase 2
Intervention: Not specified
Conditions: Advanced or Recurrent Solid Tumors
Sponsor: National Cancer Center, Japan
Enrollment: 75
Locations: 7
Primary Endpoint: Objective response rate (ORR)
Status: Recruiting
Last Updated: 7 months ago

Overview Investigators Eligibility Criteria Outcomes Sites Similar Trials

Overview

Brief Summary

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).

Registry

clinicaltrials.gov

Start Date

June 15, 2021

End Date

March 31, 2028

Last Updated

7 months ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

National Cancer Center, Japan

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•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
•Ineffective to or intolerant to initial treatment, or for which standard treatment is no longer available
•Participants with an FGFR gene alteration detected by NGS panel, who fall under one of the categories of groups A to C and E defined as below
•Group A: FGFR1-3 fusion
•Group B and E: FGFR1-3 specific activating mutations as below;
•FGFR1: P150S, T340M, R445W, N546K, K656E
•FGFR2: C62Y, A67V, N82K, D101Y, E160K, E163K, M186T, R203H, R210Q, Q212K, R251Q, S252W, P253R, P253L, A264T, W290C, K310R, Y328N, G364E, Y375C, C382R, A389T, V392A, R399Q, H416R, I422V, H544Q, N549H, N549K, N549D, N549S, L560F, K659E, K659N, R664W, E718K, S791T
•FGFR3: G380E, G380R, A391E, K650T, K650E, K650Q, K650N
•Group C: FGFR1-3 activating mutation not applicable to group B, or FGFR1, 2 gene amplification
•For Group D, participants with cholangiocarcinoma who have previously received a selective FGFR inhibitor other than E7090 and have demonstrated progressive disease or resistance

Exclusion Criteria

•Participants with brain, subdural or leptomeningeal metastases
•Participants with primary CNS tumor located in either cerebellum, brainstem, spinal cord, pituitary gland, optic nerve or olfactory nerve
•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)
•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)
•Child-Pugh score B or C
•Participants with pericardial effusion, pleural effusion, or ascites requiring treatment
•Have any of the following ocular diseases
•Grade 2 or higher corneal disorders
•Active retinopathy (e.g., age-related macular degeneration, central serous chorioretinal disease, retinal tear)
•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

Outcomes

Primary Outcomes

Objective response rate (ORR)

Time Frame: Baseline up to 3.5 years

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 Outcomes

Objective response rate (ORR)(Baseline up to 3.5 years)
Progression-free survival (PFS)(Baseline up to 3.5 years)
Disease control rate (DCR)(Baseline up to 3.5 years)
Overall Survival (OS)(Baseline up to 3.5 years)
Adverse reaction (adverse drug reaction) rate(From the first dose of the investigational product until 30 days after the last dose of study drugs)
Duration of response (DOR)(Baseline up to 3.5 years)
Adverse event (AE) rate(From the first dose of the investigational product until 30 days after the last dose of study drugs)
Time to response (TTR)(Baseline up to 3.5 years)