NCCH2006/MK010 trial

JRCT ID: jRCT2031210043

Registered date:20/04/2021

Basic Information

• Recruitment status: Not Recruiting
• Health condition(s) or Problem(s) studied: advanced or recurrent solid tumor with fibroblast growth factor receptor (FGFR) gene alteration
• Date of first enrollment: 09/07/2021
• Target sample size: 45
• Study type: Interventional
• Intervention(s): 140 mg of E7090 is orally administered once daily.

Outcome(s)

• Primary Outcome: Objective response rate
• Secondary Outcome: objective response rate (by site), progression-free survival, overall survival, disease control rate, adverse event rate, adverse reaction (adverse drug reaction) rate, duration of response, and time to response

Key inclusion & exclusion criteria

• Age minimum: >= 20age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

1) Subjects 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 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
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) Age >= 20 years
6) Karnofsky Performance Status (KPS) >= 70 for patients with primary CNS tumors. Performance Status (ECOG) 0-1 for patients with non-primary CNS tumors
7) 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 measureable lesion
8) 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)
9) Laboratory tests performed within 28 days prior to enrollment (the same day of the week 4 weeks prior to the enrollment date is acceptable) fulfill the following (1)-(10), without any administration of granulocyte colony-stimulating factor (G-CSF formulation) or blood transfusion within 14 days before the blood collection date
(1) Absolute neutrophil count >= 1,500/mm^3
(2) Platelet count >= 10.0 x 10^4/mm^3
(3) Hemoglobin >= 8.0 g/dL
(4) Total bilirubin <= 2.25 mg/dL
(5) AST <= 90 U/L; if intrahepatic cholangiocarcinoma or liver metastasis present, <= 150 U/L
(6) ALT <= 126 U/L (men)/<= 69 U/L (women); if intrahepatic cholangiocarcinoma or liver metastasis present, 210 U/L (men)/<= 115 U/L (women)
(7) Creatinine <= 1.6 mg/dL (men)/<= 1.2 mg/dL (women)
(8) International normalized ratio (INR) <=1.5
(9) Corrected calcium <= 10.1 mg/dL
(10) 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

Exclude criteria

1) Participants with brain or subdural metastases
2) Participants with leptomeningeal metastasis
3) Participants with primary spinal cord tumors
4) Participants with primary CNS tumor located in either cerebellum, brainstem, pituitary gland, optic nerve or olfactory nerve
5) 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)
6) 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)
7) Child-Pugh score B or C
8) Participants with pericardial effusion, pleural effusion, or ascites requiring treatment
9) Have any of the following ocular diseases
a)Grade 2 or higher corneal disorders
b)Active retinopathy (e.g., age-related macular degeneration, central serous chorioretinal disease, retinal tear)
10) 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
11) Participants who received a prior selective FGFR inhibitor in the recurrent/metastatic disease setting; except for patients with cholangiocarcinoma harboring FGFR2 fusion (Arm D). Note that prior use of a multi-kinase inhibitor which includes anti-FGFR activity is acceptable after review by the lead investigator
12) Participants who are receiving CYP3A inhibitors or inducers and must continue the drug due to underlying conditions during the study treatment period. If patients are to be enrolled, they must discontinue the drug at least 7 days prior to enrollment of this study
13) The presence of FGFR gatekeeper mutations as follows:
FGFR1 V561, FGFR2 V564/565, FGFR3 V555/557, FGFR4 V550
14) The presence of any of the following coexisting driver gene abnormalities:
-Genetic mutations (excluding VUS): KRAS, NRAS, EGFR, and BRAF V600
-Gene translocations ALK, ROS1, and NTRK
15) Impairment of gastrointestinal (GI) function or GI disease that may significantly after the absorption of oral E7090 (ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, small bowel resection)

Related Information

• Primary Sponsor: Takahashi Masamichi
• Source(s) of Monetary Support: Eisai Co., Ltd.