Clinical trial NCT04238715: 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 FGFR 2 Gene Fusion
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Cholangiocarcinoma
Keywords: E7090
Cholangiocarcinoma
Unresectable cholangiocarcinoma
Metastatic cholangiocarcinoma
Fibroblast Growth Factor Receptor 2 (FGFR2)
FGFR2 gene fusion
Lead sponsor: Eisai Inc.
Sponsor class: INDUSTRY
First posted: 2020-01-23
Enrollment: 63
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.


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)

   a. Prior adjuvant chemotherapy is allowed if relapse was within 6 months after last administration.
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 during study treatment (there must be a time interval of \>= 7 days since the final use of these drugs or foods by the start of study treatment).

Primary outcomes:
measure: ORR
timeFrame: 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 6 years 2 months)
Secondary outcomes:
measure: Progression Free Survival (PFS)
timeFrame: 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 6 years 2 months)
measure: Duration of Response (DOR)
timeFrame: 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 6 years 2 months)
measure: Time to Response (TTR)
timeFrame: from the date of first study dose to the date of first documentation of CR or PR (up to approximately 6 years 2 months)
measure: Overall Survival (OS)
timeFrame: From the date of first dose to the date of death from any cause (up to approximately 6 years 2 months)
measure: Disease Control Rate (DCR)
timeFrame: 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 6 years 2 months)
measure: Clinical Benefit Rate (CBR)
timeFrame: 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 6 years 2 months)
Other outcomes:
Locations:
city: Bengbu
country: China
facility: The First Affiliated Hospital of Bengbu Medical College
state: Anhui
city: Hefei
country: China
facility: Anhui Provincial Hospital
state: Anhui
city: Beijing
country: China
facility: Beijing Tsinghua Chang Gung Memorial Hospital
state: Beijing
city: Beijing
country: China
facility: Beijing Youan Hospital Affiliated to Capital Medical University
state: Beijing
city: Beijing
country: China
facility: Beijng Cancer Hospital
state: Beijing
city: Beijing
country: China
facility: Cancer Hospital Chinese Academy of Medical Sciences
state: Beijing
city: Beijing
country: China
facility: Peking Union Medical University Hospital
state: Beijing
city: Fuzhou
country: China
facility: Fujian Provincial Hospital
state: Fujian
city: Xiamen
country: China
facility: The First Affiliated Hospital of Xiamen University
state: Fujian
city: Guangzhou
country: China
facility: Guangdong Province Traditional Chinese Medical Hospital
state: Guangdong
city: Guangzhou
country: China
facility: The First Affiliated Hospital, Sun Yat-sen Univeristy
state: Guangdong
city: Shenzhen
country: China
facility: Peking University Shenzhen Hospital
state: Guangdong
city: Baoding
country: China
facility: Affiliated Hospital of Hebei University
state: Hebei
city: Harbin
country: China
facility: Affilicataed Cancer Hospital of Harbin Medical University
state: Heilongjiang
city: Zhengzhou
country: China
facility: Henan Cancer Hospital
state: Henan
city: Zhengzhou
country: China
facility: The First Affiliated Hospital of Zhengzhou University
state: Henan
city: Wuhan
country: China
facility: Tongji Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology
state: Hubei
city: Wuhan
country: China
facility: Union Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology
state: Hubei
city: Changsha
country: China
facility: Hunan provincial people's hospital
state: Hunan
city: Changsha
country: China
facility: The Third Xiangya Hospital of Central South University
state: Hunan
city: Changsha
country: China
facility: Xiangya Hospital of Central South University
state: Hunan
city: Nanjing
country: China
facility: Jiangsu Province Hospital
state: Jiangsu
city: Nantong
country: China
facility: Nantong Tumor Hospital
state: Jiangsu
city: Suzhou
country: China
facility: The First Affiliated Hospital of Soochow
state: Jiangsu
city: Changchun
country: China
facility: Jilin Cancer Hospital
state: Jilin
city: Jinan
country: China
facility: Shandong Cancer Hospital
state: Shandong
city: Shanghai
country: China
facility: Fudan University Shanghai Cancer Center
state: Shanghai
city: Shanghai
country: China
facility: Zhongshan Hospital Fudan University
state: Shanghai
city: Chengdu
country: China
facility: West China Hospital of Sichuan University
state: Sichuan
city: Hangzhou
country: China
facility: The First Affiliated Hospital, College of Medicine, Zhejiang University
state: Zhejiang
city: Hangzhou
country: China
facility: The Second Affiliated Hospital, Zhejiang University School of Medicine
state: Zhejiang
city: Ningbo
country: China
facility: Ningbo First Hospital
state: Zhejiang
city: Nagoya
country: Japan
facility: Eisai Trial Site 10
state: Aichi
city: Kashiwa
country: Japan
facility: Eisai Trial Site 16
state: Chiba
city: Matsuyama
country: Japan
facility: Eisai Trial Site 11
state: Ehime
city: Matsuyama
country: Japan
facility: Eisai Trial Site 14
state: Ehime
city: Sapporo
country: Japan
facility: Eisai Trial Site 2
state: Hokkaido
city: Kanazawa
country: Japan
facility: Eisai Trial Site 8
state: Ishikawa
city: Yokohama
country: Japan
facility: Eisai Trial Site 7
state: Kanagawa
city: Tsu
country: Japan
facility: Eisai Trial Site 23
state: Mie
city: Sendai
country: Japan
facility: Eisai Trial Site 22
state: Miyagi
city: Hirakata
country: Japan
facility: Eisai Trial Site 13
state: Osaka
city: Suita
country: Japan
facility: Eisai Trial Site 17
state: Osaka
city: Sunto-gun
country: Japan
facility: Eisai Trial Site 9
state: Shizuoka
city: Bunkyo-ku
country: Japan
facility: Eisai Trial Site 5
state: Tokyo
city: Chuo-ku
country: Japan
facility: Eisai Trial Site 4
state: Tokyo
city: Koto-ku
country: Japan
facility: Eisai Trial Site 6
state: Tokyo
city: Mitaka
country: Japan
facility: Eisai Trial Site 3
state: Tokyo
city: Ube-Shi
country: Japan
facility: Eisai Trial Site 1
state: Yamaguchi
city: Chiba
country: Japan
facility: Eisai Trial Site 18
city: Fukuoka
country: Japan
facility: Eisai Trial Site 15
city: Kagoshima
country: Japan
facility: Eisai Trial Site 20
city: Kochi
country: Japan
facility: Eisai Trial Site 19
city: Kyoto
country: Japan
facility: Eisai Trial Site 12
city: Niigata
country: Japan
facility: Eisai Trial Site 21
city: Wakayama
country: Japan
facility: Eisai Trial Site 24
Study officials:
References: