UMIN-CTR Clinical Trial

Basic information
Public title	Validation study of the prognostic and predictive value of TP53 signature for breast cancer
Acronym	Validation study of the prognostic and predictive value of TP53 signature for breast cancer
Scientific Title	Validation study of the prognostic and predictive value of TP53 signature for breast cancer
Scientific Title:Acronym	Validation study of the prognostic and predictive value of TP53 signature for breast cancer
Region	Japan

Condition
Condition	Breast Cancer
Classification by specialty	Hematology and clinical oncology Breast surgery
Classification by malignancy	Malignancy
Genomic information	NO

Objectives
Narrative objectives1	The aim of this study is to validate whether the TP53 status diagnosed by the TP53 signature diagnostic kit can predict the prognosis and the therapeutic effect of neoadjuvant chemotherapy in breast cancer patients.
Basic objectives2	Efficacy
Basic objectives -Others
Trial characteristics_1	Confirmatory
Trial characteristics_2
Developmental phase	Not applicable

Assessment
Primary outcomes	Pathological complete response rate
Key secondary outcomes

Base
Study type	Observational

Study design
Basic design
Randomization
Randomization unit
Blinding
Control
Stratification
Dynamic allocation
Institution consideration
Blocking
Concealment

Intervention
No. of arms
Purpose of intervention
Type of intervention
Interventions/Control_1
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

Eligibility
Age-lower limit	Not applicable
Age-upper limit	Not applicable
Gender	Female
Key inclusion criteria	The subjects are the patients enrolled in the following five clinical trials conducted by JBCRG and OOTR. i. JBCRG-01 (n=202) ii. JBCRG-02 (n=31) iii. JBCRG-02' (n=19) iv. JBCRG-03 (n=130) v. OOTR-N003 (n=500) In addition, perioperative chemotherapy-free hormone receptor positive breast cancer (HR+BC) patients will be collected targeting at 340 cases. Selection criteria for perioperative chemotherapy-free HR+BC cases are as follows according to the eligibility criteria of the above five clinical trials. Cases that satisfy all the following 1 to 7 1. Cases with histologically confirmed primary breast cancer (invasive cancer) and undergone curative resection 2. Cases in which TNM at diagnosis satisfies the following {cT1 c-3 cN0 cM0 (> 1 cm) / cT1-3 cN1 cM0} 3. Cases in which chemotherapy were not given as preoperative or postoperative adjuvant therapy (cases in which endocrine therapy were given are acceptable) 4. 20 years old or older and less than 70 years old 5. Cases in which regular follow-up has been performed at the facility where surgery for breast cancer was performed and of whom sufficient prognostic information can be obtained (Follow-up period must be over 5 years in cases without recurrence). 6. Cases in which the following samples can be submitted Cases with preoperative endocrine therapy: Biopsy tumor samples obtained before endocrine therapy (formalin fixed paraffin embedded tissue, total of 12 slides of 4 micro meter thick unstained specimens) Cases without preoperative endocrine therapy: Biopsy tumor samples at diagnosis or tumor samples resected by surgery (formalin fixed paraffin embedded tissue, total of 12 slides of 4 micro meter thick unstained specimens) 7. Cases diagnosed with primary breast cancer between August 2005 and July 2009 The number of cases in each facility is limited to 60 cases, and all eligible cases after August 2005 have to be registered consecutively.
Key exclusion criteria	1. Male 2. Cases judged by investigator to be unfit to be enrolled into the study
Target sample size	840

Research contact person
Name of lead principal investigator	1st name Chikashi Middle name Last name Ishioka
Organization	Institute of Development, Aging and Cancer, Tohoku University
Division name	Department of Clinical Oncology
Zip code	980-8575
Address	4-1, Seiryo-machi, Aobaku, Sendai, Miyagi, Japan
TEL	022-717-8543
Email	chikashi@tohoku.ac.jp

Public contact
Name of contact person	1st name Shin Middle name Last name Takahashi
Organization	Institute of Development, Aging and Cancer, Tohoku University
Division name	Department of Clinical Oncology
Zip code	980-8575
Address	4-1, Seiryo-machi, Aobaku, Sendai, Miyagi, Japan
TEL	022-717-8543
Homepage URL
Email	shin.takahashi.e7@tohoku.ac.jp

Sponsor
Institute	Japan Agency for Medical Research and Development
Institute
Department

Funding Source
Organization	Japan Agency for Medical Research and Development
Organization
Division
Category of Funding Organization	Japanese Governmental office
Nationality of Funding Organization

Other related organizations
Co-sponsor
Name of secondary funder(s)

IRB Contact (For public release)
Organization	Tohoku University Hospital Research Ethics Committee
Address	1-1, Seiryo-machi, Aobaku, Sendai, Miyagi, Japan
Tel	022-728-4105
Email	ec@rinri.hosp.tohoku.ac.jp

Secondary IDs
Secondary IDs	NO
Study ID_1
Org. issuing International ID_1
Study ID_2
Org. issuing International ID_2
IND to MHLW

Institutions
Institutions

Other administrative information
Date of disclosure of the study information	2019 Year 09 Month 18 Day

Related information
URL releasing protocol
Publication of results	Partially published

Result
URL related to results and publications
Number of participants that the trial has enrolled	800
Results	A total of 800 specimens were collected from 23 sites in Japan, and TP53 signature data were obtained for a total of 753 cases, excluding insufficient specimen cases (wild-type (wt) 361 cases and mutant (mt) 392 cases).In a preoperative chemotherapy cohort, the pCR ratio in the mt group was significantly higher than that of wt group (the estimate of the common odds ratio of the mt group for the wt group: 5.599, 95% CI: 1.876-16.705, p=0.0008).
Results date posted	2021 Year 07 Month 27 Day
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

Progress
Recruitment status	Completed
Date of protocol fixation	2019 Year 09 Month 10 Day
Date of IRB	2019 Year 09 Month 26 Day
Anticipated trial start date	2019 Year 09 Month 26 Day
Last follow-up date	2021 Year 03 Month 31 Day
Date of closure to data entry	2021 Year 03 Month 31 Day
Date trial data considered complete	2021 Year 03 Month 31 Day
Date analysis concluded	2021 Year 03 Month 31 Day

Other

Other related information

We verify that the pCR ratio in patients diagnosed with mt by TP53 signature is higher than that in patients diagnosed with wt in patients treated with preoperative chemotherapy. To match the patients background between TP53 signature status, we use propensity score (PS) estimated by logistic regression analysis. The covariates are ER, PgR, Ki67, age, menopausal status, tumor diameter, lymph node status and vascular invasion. We divide patients into 3 groups by PS so that the number of patients in the stratum is equal. The pCR ratio, the 95% confidence interval by the Cloper-Pearson method and the odds ratio are calculated in the patients with mt and wt by TP53 signature, respectively. In addition, the null hypothesis that the common odds ratio is 1 is tested at a two-sided significance level of 5% using the Mantel-Haenszel test.

Management information
Registered date	2019 Year 07 Month 26 Day
Last modified on	2021 Year 07 Month 27 Day

Link to view the page
URL(English)	https://upload.umin.ac.jp/cgi-open-bin/icdr_e/ctr_view.cgi?recptno=R000042740