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

Sponsor

Eisai Co., Ltd. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04238715

Collaborator

(none)

Enrollment

Locations

Arm

42.3

Anticipated Duration (Months)

1.1

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Cholangiocarcinoma	Drug: E7090	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

60 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Multicenter, Open-Label, Phase 2 Trial of E7090 in Subjects With Unresectable Advanced or Metastatic Cholangiocarcinoma With FGFR 2 Gene Fusion

Actual Study Start Date :

Jan 22, 2020

Anticipated Primary Completion Date :

Feb 1, 2023

Anticipated Study Completion Date :

Aug 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: E7090 140 mg Participants 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.	Drug: E7090 E7090 tablets orally.

Arm

Intervention/Treatment

Experimental: E7090 140 mg

Participants 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.

Drug: E7090

E7090 tablets orally.

Outcome Measures

Primary Outcome Measures

ORR [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 years 11 months)]
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 (targeted and non-target [NT]) 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 (NT) lesions.

Secondary Outcome Measures

Progression Free Survival (PFS) [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 years 11 months)]
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 progressive disease (PD) or date of death from any cause, whichever occurs first. PD per RECIST 1.1 is defined as at least a 20% relative increase and 5 mm absolute increase in the sum of diameters of target lesions (taking as reference the smallest sum on study) recorded since the treatment started or the appearance of 1 or more new lesions.
Duration of Response (DOR) [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 years 11 months)]
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.
Time to Response (TTR) [from the date of first study dose to the date of first documentation of CR or PR (up to approximately 2 years 11 months)]
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.
Overall Survival (OS) [From the date of first dose to the date of death from any cause (up to approximately 2 years 11 months)]
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.
Disease Control Rate (DCR) [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 years 11 months)]
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.
Clinical Benefit Rate (CBR) [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 years 11 months)]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

20 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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.
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.
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)

Prior adjuvant chemotherapy is allowed if relapse was within 6 months after last administration.

Measurable disease meeting the following criteria:
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).
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.
Corrected serum calcium less than or equal to (<=) upper limit of normal (ULN).
Phosphate <=ULN.
Participants with Performance Status (PS) score of 0-1 established by Eastern Cooperative Oncology Group (ECOG).
Participants who are expected to survive for 3 months or longer after starting administration of the investigational drug.
Washout period required from the end of prior treatment to the start of E7090 administration will be as follows
Antibody and other investigational drugs : >=4 weeks
Prior chemotherapy (except small-molecule targeted therapy), surgical therapy, radiation therapy：>=3 weeks
Endocrine therapy, immunotherapy, small-molecule targeted therapy: >=2 weeks

Exclusion Criteria:

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.
Concomitant active infection requiring systemic treatment (except hepatitis B or C virus-infected participants who are under anti-viral treatment).
Participants who test positive for human immunodeficiency virus (HIV antibody) at Screening 2.
Child-Pugh score B or C.
Moderate or severe ascites extending from the pelvis to the liver surface.
Following ocular disorders
Current evidence of Grade 2 or higher corneal disorder
Current evidence of active macula disorder (example: age-related macular degeneration, central serous chorioretinal disease)
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.
Participants with prior therapy targeting FGFR2.
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).

Contacts and Locations

Locations

	Site	City	State	Country
1	The First Affiliated Hospital of Bengbu Medical College	Bengbu	Anhui	China
2	Anhui Provincial Hospital	Hefei	Anhui	China
3	Beijing Tsinghua Chang Gung Memorial Hospital	Beijing	Beijing	China
4	Beijing Youan Hospital Affiliated to Capital Medical University	Beijing	Beijing	China
5	Beijng Cancer Hospital	Beijing	Beijing	China
6	Cancer Hospital Chinese Academy of Medical Sciences	Beijing	Beijing	China
7	Peking Union Medical University Hospital	Beijing	Beijing	China
8	Fujian Provincial Hospital	Fuzhou	Fujian	China
9	The First Affiliated Hospital of Xiamen University	Xiamen	Fujian	China
10	Guangdong Province Traditional Chinese Medical Hospital	Guangzhou	Guangdong	China
11	The First Affiliated Hospital, Sun Yat-sen Univeristy	Guangzhou	Guangdong	China
12	Peking University Shenzhen Hospital	Shenzhen	Guangdong	China
13	Affiliated Hospital of Hebei University	Baoding	Hebei	China
14	Affilicataed Cancer Hospital of Harbin Medical University	Harbin	Heilongjiang	China
15	Henan Cancer Hospital	Zhengzhou	Henan	China
16	The First Affiliated Hospital of Zhengzhou University	Zhengzhou	Henan	China
17	Tongji Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology	Wuhan	Hubei	China
18	Union Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology	Wuhan	Hubei	China
19	Hunan provincial people's hospital	Changsha	Hunan	China
20	The Third Xiangya Hospital of Central South University	Changsha	Hunan	China
21	Xiangya Hospital of Central South University	Changsha	Hunan	China
22	Jiangsu Province Hospital	Nanjing	Jiangsu	China
23	Nantong Tumor Hospital	Nantong	Jiangsu	China
24	The First Affiliated Hospital of Soochow	Suzhou	Jiangsu	China
25	Jilin Cancer Hospital	Changchun	Jilin	China
26	Shandong Cancer Hospital	Jinan	Shandong	China
27	Fudan University Shanghai Cancer Center	Shanghai	Shanghai	China
28	Zhongshan Hospital Fudan University	Shanghai	Shanghai	China
29	West China Hospital of Sichuan University	Chengdu	Sichuan	China
30	The First Affiliated Hospital, College of Medicine, Zhejiang University	Hangzhou	Zhejiang	China
31	The Second Affiliated Hospital, Zhejiang University School of Medicine	Hangzhou	Zhejiang	China
32	Ningbo First Hospital	Ningbo	Zhejiang	China
33	Eisai Trial Site 10	Nagoya	Aichi	Japan
34	Eisai Trial Site 16	Kashiwa	Chiba	Japan
35	Eisai Trial Site 11	Matsuyama	Ehime	Japan
36	Eisai Trial Site 14	Matsuyama	Ehime	Japan
37	Eisai Trial Site 2	Sapporo	Hokkaido	Japan
38	Eisai Trial Site 8	Kanazawa	Ishikawa	Japan
39	Eisai Trial Site 7	Yokohama	Kanagawa	Japan
40	Eisai Trial Site 23	Tsu	Mie	Japan
41	Eisai Trial Site 22	Sendai	Miyagi	Japan
42	Eisai Trial Site 13	Hirakata	Osaka	Japan
43	Eisai Trial Site 17	Suita	Osaka	Japan
44	Eisai Trial Site 9	Sunto-gun	Shizuoka	Japan
45	Eisai Trial Site 5	Bunkyo-ku	Tokyo	Japan
46	Eisai Trial Site 4	Chuo-ku	Tokyo	Japan
47	Eisai Trial Site 6	Koto-ku	Tokyo	Japan
48	Eisai Trial Site 3	Mitaka	Tokyo	Japan
49	Eisai Trial Site 1	Ube-Shi	Yamaguchi	Japan
50	Eisai Trial Site 18	Chiba		Japan
51	Eisai Trial Site 15	Fukuoka		Japan
52	Eisai Trial Site 20	Kagoshima		Japan
53	Eisai Trial Site 19	Kochi		Japan
54	Eisai Trial Site 12	Kyoto		Japan
55	Eisai Trial Site 21	Niigata		Japan
56	Eisai Trial Site 24	Wakayama		Japan