UMIN-CTR Clinical Trial

Public title

The study of the significance of the phosphorylation of p53 Ser46 in the prediction of response to preoperative chemotherapy or chemoradiotherapy for advanced esophageal cancer

Acronym

The study of the significance of p53 Ser46-P in the prediction of response to preoperative treatment for advanced esophageal cancer

Scientific Title

The study of the significance of the phosphorylation of p53 Ser46 in the prediction of response to preoperative chemotherapy or chemoradiotherapy for advanced esophageal cancer

Scientific Title:Acronym

The study of the significance of p53 Ser46-P in the prediction of response to preoperative treatment for advanced esophageal cancer

Region

Japan

Condition

Advanced esophageal squamous cell carcinoma which are scheduled to undergo chwemotherapy or chemoradiotherapy as an initial treatment

Classification by specialty

Gastrointestinal surgery

Classification by malignancy

Malignancy

Genomic information

NO

Narrative objectives1

Advanced esophageal cancer is recently treated by multimodality therapy, therefore, it is an urgent issue to establish a therapy for individual based on the prediction of treatment response. The researches conducted so far revealed that mutant P53 has a close association with poor or no response to therapy. However, patinets with wild-type P53 did not always show good response, speculating that the phosphorylation of P53 Ser-46, which is the active form of P53 inducing apoptosis, is likely to be required. Consequently, the first step of this study is aimed to investigate the usefulness of phosphorylation of P53 Ser-46 as a prediction factor of treatment response. Next, the second step of this study is designed to improve the indivsualized therapy on the treatment outcome and QOL on the basis of the P53 genotype and the induction of phosphorylation of P53 Ser-46.

Basic objectives2

Safety,Efficacy

Basic objectives -Others

Trial characteristics_1

Exploratory

Trial characteristics_2

Pragmatic

Developmental phase

Phase I,II

Primary outcomes

the correlation between the phosphorylation of P53 Ser-46 and complete response to therapy

Key secondary outcomes

1. the correlation between the phosphorylation of P53 Ser-46 and clinical good response (CR and PR)
2. the correlation between the phosphorylation of P53 Ser-46 and histological complete response
3. the correlation between the phosphorylation of P53 Ser-46 and P53 genotype
4. the correlation between the phosphorylation of P53 Ser-46 and the prognosis
5. the correlation between the phosphorylation of P53 Ser-46 and failure patterns
6. the comparison of P53 status in pretreatment tumor and residual or local recurrent tumor after treatment

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

Diagnosis

Type of intervention

Maneuver

Interventions/Control_1

Tumor tissue is taken by biopsy with endoscopy within the first day and the third day of preoperative chemotherapy or chemoradiotherapy.

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. histologically confirmed esophageal squamous cell carcinoma.
2. M0, however, M1LYM of the supraclavicular lymph nodes is eligble.
3. no history of chemotherapy or radiotherapy.
4. irrespective of whether or not tumor can be resected.
5. at age 20 years or over.
6. performance status of 0 or 1.
7. good function of main organs.
8. meet the criteria of laboratory data before enrollment. WBC 3,000 or more and less than 12,000/mm3
Neutrophil 1,500/mm3 or more
Platelet 100,000/mm3 or more
Hb 9g/dl or more
Total bilirubin 1.2mg/dl or less
AST and ALT within 2 times of the
normal upper limit of the institution
9. cleatinine clearance 60ml/min or more
10. SpO2 95% or more in room air
11. Written informed consent is obtained.

Key exclusion criteria

1. another malignat disease to need treatment
2. past hostory of severe drug hypersensitivity
3. pregnant female, nursing mother and women who have childbearing potential and are considering pregnancy.
4. doctor rules unfit for enrollment of this study.

Target sample size

30

Name of lead principal investigator

1st name
Middle name
Last name	Takushi Yasuda

Organization

Kindai University, Faculty of Medicine

Division name

Department of Surgery

Zip code

Address

377-2, Ohno-Higashi, Osaka-Sayama, Osaka

TEL

072-366-0221

Email

tyasuda@surg.med.kindai.ac.jp

Name of contact person

1st name
Middle name
Last name	Takushi Yasuda

Organization

Kindai University, Faculty of Medicine

Division name

Department of Surgery

Zip code

Address

377-2, Ohno-Higashi, Osaka-Sayama, Osaka

TEL

072-366-0221

Homepage URL

http://www.kindai-geka.jp/

Email

tyasuda@surg.med.kindai.ac.jp

Institute

Kindai University, Faculty of Medicine, Department of Surgery

Institute

Department

Personal name

Organization

Japan Society for the Promotion of Science

Organization

Division

Category of Funding Organization

Japanese Governmental office

Nationality of Funding Organization

Co-sponsor

Name of secondary funder(s)

Organization

Address

Tel

Email

Secondary IDs

NO

Study ID_1

Org. issuing International ID_1

Study ID_2

Org. issuing International ID_2

IND to MHLW

Institutions

近畿大学医学部附属病院（大阪府）

Date of disclosure of the study information

2015

Year

02

Month

13

Day

URL releasing protocol

Publication of results

Unpublished

URL related to results and publications

Number of participants that the trial has enrolled

Results

In this study, we examined the usefulness of induction of the phosphorylation of p53-Ser46 the next day after initiation of treatment as a biomarker of the prediction of treatment response of chemotherapy/chemoradiotherapy for esophageal squamous cell carcinoma. We confirmed the fact for the first time that the phosphorylation of p53-Ser-46 was induced by chemotherapy/chemoradiotherapy in the early stage of treatment. However, there was no significant correlation between the phosphorylation of p-53-Ser-46 and treatment response. Among cases obtained complete response to preoperative therapy, the cases with p-53 mutant and no induction of Ser-46 phosphorylation were involved, therefore, these results suggested that the effect on chemotherapy and chemoradiotherapy was caused not only by apoptosis thorough p53 pathway, but also by another pathway associating with other factors.

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

Completed

Date of protocol fixation

2014

Year

09

Month

10

Day

Date of IRB

Anticipated trial start date

2015

Year

02

Month

13

Day

Last follow-up date

Date of closure to data entry

Date trial data considered complete

2016

Year

03

Month

31

Day

Date analysis concluded

2017

Year

01

Month

30

Day

Other related information

Registered date

2015

Year

02

Month

13

Day

Last modified on

2017

Year

02

Month

14

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000019011