UMIN-ICDS Clinical Trial

Public title

Randomized Controlled Phase 2 Clinical Trial of JPH203 in Patients With Advanced Biliary Tract Cancers.

Acronym

JPH203-SBECD-P2

Scientific Title

Randomized Controlled Phase 2 Clinical Trial of JPH203 in Patients With Advanced Biliary Tract Cancers.

Scientific Title:Acronym

JPH203-SBECD-P2

Region

Japan

Condition

Advanced Biliary Tract Cancers

Classification by specialty

Hepato-biliary-pancreatic medicine

Classification by malignancy

Malignancy

Genomic information

NO

Narrative objectives1

To evaluate the efficacy and safety of JPH203 (25 mg/m2) or Placebo in patients with advanced biliary tract cancers.

Basic objectives2

Efficacy

Basic objectives -Others

Trial characteristics_1

Trial characteristics_2

Developmental phase

Phase II

Primary outcomes

Progression Free Survival (PFS) by blinded independent central review

Key secondary outcomes

Study type

Interventional

Basic design

Parallel

Randomization

Randomized

Randomization unit

Individual

Blinding

Double blind -all involved are blinded

Control

Placebo

Stratification

Dynamic allocation

Institution consideration

Blocking

Concealment

No. of arms

2

Purpose of intervention

Treatment

Type of intervention

Medicine

Interventions/Control_1

The administration of study drug (JPH203-SBECD, 25mg/m2) is performed (repeated dose for 5days + cession for 9days).

Interventions/Control_2

The administration of Placebo is performed (repeated dose for 5days + cession for 9days).

Interventions/Control_3

Interventions/Control_4

Interventions/Control_5

Interventions/Control_6

Interventions/Control_7

Interventions/Control_8

Interventions/Control_9

Interventions/Control_10

Age-lower limit

20

years-old

<=

Age-upper limit

Not applicable

Gender

Male and Female

Key inclusion criteria

1) Patient or legally acceptable representative (in case it is difficult to obtain consent from patient due to the lack of consent abillity) whose written informed consent has been obtained for enrollment as a subject for the clinical trial.
2) Japanese patient whose age is older than 20 years at the agreement.
3) Patient diagnosed cytologicallyor histologically as biliary tract cancer (carcinoma of the intrahepatic bile duct, extrahepatic bile duct, gallbladder, and ampulla of Vater).
4) Histologically proven adenocarcinoma or adenosquamous carcinoma for patients with EHBD, GB, or AV carcinomas, or adenocarcinoma for IHBD carcinomas.
5) Patient with unresectable biliary tract cancer or recurrent biliary tract cancer.
6) Patient who has measurable regions by RECIST version 1.1 before 4 weeks from the date of enrollment.
7) Patient with standard therapy ineffective or intolerable.
8) Patient whose EOCG performance state is 0-1.

Key exclusion criteria

1) Patient with severe disorders and/or unstable complications except cancers evaluated by investigator.
2) Patient with infection required systemic therapy.
3) Patient with positive HIV-1 antibody or HBs antigen or HCV-RNA.
4) Patient with ECG abnormality
5) Patient with pleural fluids, pericardial effusions or ascites required drainage

Target sample size

81

Name of lead principal investigator

1st name	Junji
Middle name
Last name	Furuse

Organization

Kyorin University Hospital

Division name

Medical Oncology

Zip code

181-8611

Address

6-20-2, Shinkawa, Mitaka-shi, Tokyo, Japan

TEL

0422-47-5511

Email

jfuruse@ks.kyorin-u.ac.jp

Name of contact person

1st name	Haruki
Middle name
Last name	Kusaka

Organization

J-Pharma Co., Ltd.

Division name

Clinical Development Department

Zip code

230-0046

Address

75-1 Onocho, Turumi-ku, Yokohama, Japan

TEL

045-506-1155

Homepage URL

Email

kusaka.h@j-pharma.com

Institute

J-Pharma Co., Ltd.

Institute

Department

Personal name

Organization

J-Pharma Co., Ltd.

Organization

Division

Category of Funding Organization

Other

Nationality of Funding Organization

Co-sponsor

Name of secondary funder(s)

Organization

Kanagawa Cancer Center IRB

Address

2-3-2 Nakao, Asahi-ku, Yokohama, Kanagawa, Japan

Tel

045-520-2222

Email

chiken-jimu4@kcch.jp

Secondary IDs

NO

Study ID_1

Org. issuing International ID_1

Study ID_2

Org. issuing International ID_2

IND to MHLW

Institutions

Date of disclosure of the study information

2018

Year

09

Month

14

Day

URL releasing protocol

Publication of results

Partially published

URL related to results and publications

https://meetings.asco.org/abstracts-presentations/217774

Number of participants that the trial has enrolled

106

Results

Results date posted

Results Delayed

Results Delay Reason

Date of the first journal publication of results

Baseline Characteristics

The median (minimum and maximum) age that patients had obtained informed consents in FAS was 68.0 (34 and 83) and 63.0 (38 and 79) years in the JPH203 and placebo groups (in that order), respectively, and the mean was 66.1 (standard deviation = 11.6) and 62.1 (standard deviation = 10.7) years. Gender was 60.9% and 60.0% for males and 39.1% and 40.0% for females, 52.2% and 51.4% for subjects with prior primary resection, and 47.8% and 48.6% for subjects without a history of prior primary resection. The subgroups of biliary tract cancer was the intrahepatic cholangiocarcinoma (IHC) in 39.1% and 48.6%, gallbladder cancer (GBC) in 23.2% and 22.9%, extrahepatic
cholangiocarcinoma (EHC) in 21.7% and 17.1%, and ampulla of Vater cancer
(AVC) in 15.9% and 11.4%.

Participant flow

Informed consent was obtained from 211
patients with 106 patients enrolled into the study. The 106 patients were randomly assigned to the JPH203 group (N=70 patients) or placebo group (N=36 patients).

One patient assigned to the placebo group discontinued the study before receiving the study drug, and 105 patients (70 pts in the JPH203 group and 35 pts in the placebo group) received the study drugs. Two patients (one in the JPH203 group and one in the placebo group) were still receiving study drug at the timing of the data cutoff, and 103 patients (69 pts in the JPH203 group and 34 pts in the placebo group) discontinued study drug in a blinded treatment period.

The number of patients in the primary endpoint analysis population, FAS was 69 pts and 54 pts in the JPH203 and placebo groups, respectively.

The number of patients in the safety analysis population, SAFETY, was 70 pts and 35 pts in the JPH203 and placebo groups, respectively.

Adverse events

The adverse events that were reported in over 5.0% in the JPH203 group were decreased appetite, malaise, cholangitis, constipation, nausea, pyrexia, diarrhea, insomnia, vomiting, cancer pain, pruritus, hypertension, and stomatitis.

Of these adverse events, those that occurred at least 5% more frequently in the JPH203 group than in the placebo group were cholangitis (10/70 pts (14.3%) in the JPH203 group and 3/35 pts (8.6%) in the placebo group) and insomnia (8/70 pts (11.6%) in the JPH203 group, and 2/35 pts (5.7%) in the placebo group).

With the exception of cholangitis and Insomnia, most of the adverse events that were reported in over 5.0% did not differ significantly between the JPH203 group and the placebo group, and were considered that there is no major safety concern.

Cholangitis was judged with no casusal relationship to the study drug by the investigators.
However in the incident rate of cholangitisto in the JPH203 group was higher than in the placebo group and the its severity is the highest, so cholangitis was the event to be considered.

Outcome measures

All time-to-event endpoints were estimated using the Kaplan-Meier method. A stratified log-rank test was used to assess statistical significance. A Cox hazard model was used to estimate the Hazard Ratio (HR) and the 95% CI for PFS, in comparing the nanvuranlat and placebo groups. Stratification of primary endpoint was BTC subtype and history of resection of the primary lesion.

In the primary endpoint of PFS according to blinded, independent central image assessment,the HR for PFS in the JPH203 group versus the placebo group was 0.557 (95% confidence interval, 0.3435-0.9029) by stratified cox proportional hazards model.The two-sided p-value by stratified log-rank test was 0.0164.

The JPH203 group significantly prolonged PFS according to blinded, independent central image assessment, the primary endpoint in the FAS, versus the placebo group.

Plan to share IPD

IPD sharing Plan description

Recruitment status

Completed

Date of protocol fixation

2018

Year

06

Month

19

Day

Date of IRB

2018

Year

09

Month

07

Day

Anticipated trial start date

2018

Year

11

Month

08

Day

Last follow-up date

2022

Year

11

Month

30

Day

Date of closure to data entry

Date trial data considered complete

Date analysis concluded

Other related information

Registered date

2018

Year

09

Month

10

Day

Last modified on

2023

Year

09

Month

30

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/icdr_e/ctr_view.cgi?recptno=R000038852