UMIN-CTR Clinical Trial

Public title

Phase II trial of bolus 5-FU/l-LV regimen as salvage line chemotherapy for oral fluorouracil resistant unresectable gastric cancer
(HGCSG1502)

Acronym

bolus 5-FU/l-LV for gastric cancer as salvage line chemotherapy (HGCSG1502 trial)

Scientific Title

Phase II trial of bolus 5-FU/l-LV regimen as salvage line chemotherapy for oral fluorouracil resistant unresectable gastric cancer
(HGCSG1502)

Scientific Title:Acronym

bolus 5-FU/l-LV for gastric cancer as salvage line chemotherapy (HGCSG1502 trial)

Region

Japan

Condition

Gastric Cancer or Cancer at the Esophagogastric Junction

Classification by specialty

Gastroenterology

Hematology and clinical oncology

Classification by malignancy

Malignancy

Genomic information

NO

Narrative objectives1

To verify the efficacy and safety of weekly bolus 5-FU and l-LV regimen for the standard treatment refractory or intolerance of unresectable advanced or recurrent gastric cancer or cancer at the esophagogastric junction

Basic objectives2

Safety,Efficacy

Basic objectives -Others

Trial characteristics_1

Exploratory

Trial characteristics_2

Pragmatic

Developmental phase

Phase II

Primary outcomes

Progression-free survival rate at the time the treatment after 8 weeks

Key secondary outcomes

response rate, disease control rate, overall survival, progression free survival, time to treatment failure, adverse events, dose intensity and QOL by EORTC QLQ-C30

Study type

Interventional

Basic design

Single arm

Randomization

Non-randomized

Randomization unit

Blinding

Open -no one is blinded

Control

Uncontrolled

Stratification

Dynamic allocation

Institution consideration

Blocking

Concealment

No. of arms

1

Purpose of intervention

Treatment

Type of intervention

Medicine

Interventions/Control_1

Patients are administrated bolus 5-FU/l-LV regimen chemotherapy consists of l-LV 250mg/m2/2h iv and 5-FU 600mg/m2 iv bolus given intravenously once weekly followed by 2-week rest period, within a 8-week cycle. It will continue as long as it does not correspond to the discontinuance criteria.
Discontinuance criteria as follows,
a. When the patient makes an offer and consent of the withdrawal of the decline of participation research from research subjects.
b. When the treatment due to adverse events directly attributable to the investigating treatment can not be resumed be postponed exceeding 28 days
c. When 2-step dose-down when it takes a rest beyond applicable for 14 days washout standards to be administered (5-FU 360mg / m2)
d. When the disease progression has been confirmed by diagnostic imaging, etc.
e. When the patient need the radiation therapy and has started.
f. When the entire present study has been discontinued.
g. When the investigator has determined that the appropriate discontinuation of this study.

Interventions/Control_2

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. it was confirmed that it is histologically adenocarcinoma, unresectable gastric cancer or recurrent gastric cancer cases (not required histological confirmation in metastases)
2. Age: 20 years of age or older.
Patient 3.ECOG PS of (Eastern Cooperative Oncology Group, Performance status) 0, 1 or 2,
4. S-1 or refractory to capecitabine against gastric cancer. However, after radical resection was enforced, if the S-1 or capecitabine was administered as adjuvant chemotherapy, it is determined that the refractory as long as it is a relapse within six months.
5. refractory or intorelance to chemotherapy, including platinum formulation (cisplatin or oxaliplatin).
6. refractory or intorelance to chemotherapy, including taxanes (paclitaxel or docetaxel).
7. refractory or intorelance to chemotherapy, including irinotecan.
8. refractory or intorelance to chemotherapy, including Ramucirumab.
9. Patients who wish to be given aggressive chemotherapy
patient
10. major organs (bone marrow, heart, lung, kidney, etc.) feature of being held
a. Neutrophil count is 1,200 / mm3 or more
b. Platelet count is 75,000 / mm3 or more
c. ALT is 3 times or less of the facility reference value upper limit. However five times or less the case with a liver metastasis.
d. T-Bil is less than 2.0mg / dl
e. Serum Cre is less than 2.0mg / dl
11. Patients can be expected to survive more than two months at the time
12. confirmed written informed consent

Key exclusion criteria

1. patients with symptomatic central nerve metastasis
2. patients with uncontrolled active infection
3. patients with uncontrollable diarrhea
4. patients with uncontrollable ischemic heart disease
5. patients with ascites that requires frequent drainage
6. patients with intestinal obstruction condition requiring sustained drainage by long tube
7. patients with other serious complications not to be able to be given anti-cancer chemotherapy
8. Patients with other overlapping malignancies that can be a prognostic factor.
9. patients with difficulty to their decision-making with severe mental disorders to be estimated.
10. pregnant, or female patients with intention of lactating and pregnancy and childbirth.
11. Male patients who are willing to let the pregnancy.
12. patients using flucytosine.
13. Patients who have undergone bolus 5-FU containing anti-cancer chemotherapy in the past for their gastric cancer.
14.S-1 and capecitabine last administration day within seven days.
15. patient during radiation therapy.
16. Other, patients attending physician has determined unsuitable for the target of the study treatment.

Target sample size

38

Name of lead principal investigator

1st name	Yoshito
Middle name
Last name	Komatsu

Organization

Hokkaido University Hospital

Division name

cancer center

Zip code

060-8648

Address

Kita-15, Nishi-5, Kita-Ku, Sapporo City, Hokkaido, Japan

TEL

+81-11-706-5657

Email

ykomatsu@ac.cyberhome.ne.jp

Name of contact person

1st name	Tetsuhito
Middle name
Last name	Muranaka

Organization

Hokkaido University Hospital

Division name

cancer center

Zip code

060-8648

Address

Kita-15, Nishi-5, Kita-Ku, Sapporo City, Hokkaido, Japan

TEL

+81-11-706-5657

Homepage URL

Email

tmuranaka@med.hokudai.ac.jp

Institute

Hokkaido University Hospital Cancer Center

Institute

Department

Personal name

Organization

Hokkaido Gastrointestinal Cancer Study Group

Organization

Division

Category of Funding Organization

Other

Nationality of Funding Organization

Japan

Co-sponsor

Name of secondary funder(s)

Organization

13) Clinical Research and Medical Innovation Center, Hokkaido University Hospital

Address

Kita-15, Nishi-5, Kita-Ku, Sapporo City, Hokkaido, Japan

Tel

011-706-7636

Email

crjimu@huhp.hokudai.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

2015

Year

09

Month

01

Day

URL releasing protocol

https://www.longdom.org/abstract/feasibility-study-of-bolus-5fluorouracillleucovorin-as-salvage-line

Publication of results

Partially published

URL related to results and publications

https://oncologypro.esmo.org/meeting-resources/esmo-asia-congress-2019/multi-centered-phase-ii-trial

Number of participants that the trial has enrolled

29

Results

Among the 29 enrolled patients, PFS rate at 8 weeks was 55.2% (95% CI 35.6% to 71.0%), which was higher than 47.5% which is the expected value of the hypothesis, and the lower limit of 95% CI is significantly higher than the threshold which is 23.1%. Grade 3 to 4 hematological adverse events (AE) were as follows; anemia 20.7%, neutropenia 3.4%, and platelet count decreased 3.4%. Grade 3 to 4 non-hematological AE were observed as follows; anorexia 20.7%, fatigue 13.8%, and diarrhea 3.4%.

Results date posted

2019

Year

09

Month

15

Day

Results Delayed

Results Delay Reason

Date of the first journal publication of results

Baseline Characteristics

Inclusion Criteria
The study subjects are patients with a diagnosis of unresectable advanced, metastatic, or recurrent gastric cancer, which have had resistance of S-1 or capecitabine, and had resistance or intolerance of cisplatin or oxalilatin, paclitaxel or docetaxel, irinotecan, and ramucirumab.

Participant flow

Participants participate in the eligible cases at the research participating facility after the researcher gives a written explanation and obtains consent by signature.

Adverse events

Grade 3 to 4 hematological adverse events (AE) were as follows; anemia 20.7%, neutropenia 3.4%, and platelet count decreased 3.4%. Grade 3 to 4 non-hematological AE were observed as follows; anorexia 20.7%, fatigue 13.8%, and diarrhea 3.4%.

Outcome measures

Among the 29 enrolled patients, PFS rate at 8 weeks was 55.2% (95% CI 35.6% to 71.0%), which was higher than 47.5% which is the expected value of the hypothesis, and the lower limit of 95% CI is significantly higher than the threshold which is 23.1%.

Plan to share IPD

IPD sharing Plan description

Recruitment status

Completed

Date of protocol fixation

2015

Year

10

Month

22

Day

Date of IRB

2015

Year

10

Month

19

Day

Anticipated trial start date

2015

Year

11

Month

13

Day

Last follow-up date

2018

Year

09

Month

30

Day

Date of closure to data entry

2018

Year

11

Month

30

Day

Date trial data considered complete

2018

Year

12

Month

31

Day

Date analysis concluded

2020

Year

03

Month

31

Day

Other related information

Registered date

2015

Year

09

Month

01

Day

Last modified on

2022

Year

09

Month

07

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000021841