UMIN-CTR Clinical Trial

Public title

Phase III study of gemcitabine, cisplatin plus S-1 combination therapy versus gemcitabine, cisplatin plus immune checkpoint inhibitor combination therapy in advanced biliary tract cancer.

Acronym

YOTSUBA trial

Scientific Title

Phase III study of gemcitabine, cisplatin plus S-1 combination therapy versus gemcitabine, cisplatin plus immune checkpoint inhibitor combination therapy in advanced biliary tract cancer.

Scientific Title:Acronym

YOTSUBA trial

Region

Japan

Condition

advanced biliary tract cancer

Classification by specialty

Hepato-biliary-pancreatic medicine	Hematology and clinical oncology	Hepato-biliary-pancreatic surgery

Classification by malignancy

Malignancy

Genomic information

NO

Narrative objectives1

This is a randomized, controlled phase III trial to investigate whether gemcitabine plus cisplatin plus S-1 (GCS) or gemcitabine plus cisplatin plus an immune checkpoint inhibitor* is a more effective standard of care for the treatment of unresectable or recurrent biliary tract cancer.

Basic objectives2

Efficacy

Basic objectives -Others

Trial characteristics_1

Trial characteristics_2

Developmental phase

Primary outcomes

Overall Survival

Key secondary outcomes

Study type

Interventional

Basic design

Parallel

Randomization

Randomized

Randomization unit

Individual

Blinding

Open -no one is blinded

Control

Active

Stratification

Dynamic allocation

Institution consideration

Blocking

Concealment

No. of arms

2

Purpose of intervention

Treatment

Type of intervention

Medicine

Interventions/Control_1

A group; GCS group; The GCS regimen comprised gemcitabine (1000 mg/m2) and cisplatin (25 mg/m2) infusion on day 1 and 80 mg/m2 of S- 1 on days 1- 7 every 2 weeks.

Interventions/Control_2

B group; GCD group; Durvalumab combined with gemcitabine and cisplatin was administered intravenously on a 21-day cycle for up to eight cycles. Durvalumab (1500 mg) was administered on day 1 of each cycle, in combination with gemcitabine (1000 mg/m2) and cisplatin (25 mg/m2), which were administered on days 1 and 8 of each cycle.

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) Histologically or cytologically diagnosed adenocarcinoma or adenosquamous carcinoma.
2) Diagnosis of unresectable or recurrent biliary tract cancer (intrahepatic cholangiocarcinoma, hilar bile duct cancer, distal cholangiocarcinoma, gallbladder cancer, or papillary carcinoma) by imaging diagnosis
3) No prior systemic chemotherapy or radiation therapy for biliary tract cancer. However, in the case of postoperative adjuvant chemotherapy for biliary tract cancer, patients are eligible if at least 6 months have passed since the date of the last dose (recurrence on the same date 6 months after the last dose is acceptable).
In the case of recurrent biliary tract cancer, any neoadjuvant chemotherapy given prior to resection is not questioned.
4) Total bilirubin < 2.9 mg/dL
5) Patients must be at least 20 years of age at the time of enrollment.
6) Patients must have a performance status (PS) of 0 or 1 according to the ECOG criteria at the time of enrollment (PS must be documented in the medical record).
7) Patients must be able to take oral intake.
8) The latest laboratory values within 14 days prior to enrollment (the same day of the week prior to enrollment is acceptable) meet all of the following criteria:
Neutrophil count > 1,500/mm3
Hemoglobin > 8.5 g/dL
Platelet count >100,000/mm3
AST <150 IU/L
ALT<150 IU/L
Creatinine <1.2 mg/dL
9) Written consent to participate in the study has been obtained from the patient.

Key exclusion criteria

1) Patients who have undergone curative resection with positive pathology margin.
2) Have active overlapping cancers (overlapping cancers that do not define the prognosis and do not require aggressive treatment, such as early-stage cancer, are acceptable).
3) Infectious diseases (excluding viral hepatitis) requiring systemic treatment. Especially, patients with biliary stasis should be enrolled after appropriate drainage and proper control of cholangitis.
4) Patients with a fever of 38 degrees Celsius. or higher at the time of enrollment.
5) Women who are pregnant, possibly pregnant, or lactating. Males who wish to have a partner who is pregnant.
6) Patients with psychiatric disorders or psychiatric symptoms that interfere with their daily life or make it difficult for them to give their consent,
difficulty in participating in the research.
7) Receiving continuous systemic administration of steroids (prednisone equivalent > 10 mg/day) or other immunosuppressive drugs for the treatment of autoimmune or other diseases.
8) Complicated by serious complications (heart failure, renal failure, liver failure, intestinal paralysis, intestinal obstruction).
9) Complicated with poorly controlled diabetes mellitus (if controlled prior to enrollment, the patient may be enrolled).
10) Complicated with unstable angina pectoris or a history of myocardial infarction within 6 months prior to enrollment.
11) Complicated interstitial pneumonia, pulmonary fibrosis, or severe emphysema, as diagnosed by CT scan of the chest.
12) Requires continued use of flucytosine, phenytoin, or warfarin potassium.
13) Patient has metastatic disease to the central nervous system (pretreatment head CT/MRI scan not required).
14) Patients with a history of hypersensitivity to any component of the study drug or any other condition that is contraindicated.
15) Patients with water diarrhea
16) Other conditions that the physician deems inappropriate for the safe conduct of this study.

Target sample size

460

Name of lead principal investigator

1st name	Tatsuya
Middle name
Last name	Ioka

Organization

Yamaguchi University Hospital

Division name

Cancer Center

Zip code

755-8505

Address

1-1-1 Minami-Kogushi, Ube, Yamaguchi

TEL

0836-22-2170

Email

ioka_ta@hotmail.com

Name of contact person

1st name	Takeshi
Middle name
Last name	Terashima

Organization

Kanazawa University Hospital

Division name

Department of Gastroenterology

Zip code

920-8641

Address

Takara-machi 13-1, Kanazawa, Ishikawa

TEL

076-265-2000

Homepage URL

Email

tera@m-kanazawa.jp

Institute

Yamaguchi University

Institute

Department

Personal name

Organization

none

Organization

Division

Category of Funding Organization

Other

Nationality of Funding Organization

Co-sponsor

Name of secondary funder(s)

Organization

Center for Clinical Research. Yamaguchi University Hospital

Address

1-1-1 Minami-Kogushi, Ube, Yamaguchi

Tel

0836-22-2428

Email

me223@yamaguchi-u.ac.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

2023

Year

08

Month

22

Day

URL releasing protocol

Publication of results

Unpublished

URL related to results and publications

Number of participants that the trial has enrolled

Results

Results date posted

Results Delayed

Results Delay Reason

Date of the first journal publication of results

Baseline Characteristics

Participant flow

Adverse events

Outcome measures

Plan to share IPD

IPD sharing Plan description

Recruitment status

Open public recruiting

Date of protocol fixation

2023

Year

06

Month

30

Day

Date of IRB

2023

Year

09

Month

01

Day

Anticipated trial start date

2023

Year

08

Month

22

Day

Last follow-up date

2029

Year

09

Month

14

Day

Date of closure to data entry

Date trial data considered complete

Date analysis concluded

Other related information

Registered date

2023

Year

07

Month

22

Day

Last modified on

2024

Year

03

Month

12

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000058983