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

Cholangiocarcinoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04238715
• Other study ID #: E7090-J000-201
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: January 22, 2020
• Est. completion date: September 1, 2024

Study information

• Verified date: March 2023
• Source: Eisai Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 63
• Est. completion date: September 1, 2024
• Est. primary completion date: September 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years and older

Eligibility

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).

Related Conditions & MeSH terms

• Cholangiocarcinoma

Intervention

Drug:
• E7090
E7090 tablets orally.

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Eisai Co., Ltd.

Countries where clinical trial is conducted

China,  Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	ORR	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.	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)
Secondary	Progression Free Survival (PFS)	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.	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)
Secondary	Duration of Response (DOR)	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.	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)
Secondary	Time to Response (TTR)	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.	from the date of first study dose to the date of first documentation of CR or PR (up to approximately 2 years 11 months)
Secondary	Overall Survival (OS)	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.	From the date of first dose to the date of death from any cause (up to approximately 2 years 11 months)
Secondary	Disease Control Rate (DCR)	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.	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)
Secondary	Clinical Benefit Rate (CBR)	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.	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)