2018/3/14 東京大学大学院医学系研究科 生物統計情報学講座
生物統計学シンポジウム 「臨床研究における生物統計家の活躍」

Est. 1962, one of six national centers in Japan

国立がん研究センターにおける生物統計家の活動と海外との連携

Missions
1. Discovering the fundamental causes of cancer
and realizing its earliest diagnosis and prevention
2. Developing innovation in medical prevention, diagnosis and treatment

Biostatisticians' activities and collaboration withforeign investigators at National Cancer Center

3. Establishing and making available the most advanced standard of care
to all patients
4. Exploring and providing the best “cancer survivorship” for patients
5. Gathering and disseminating comprehensive cancer related information

Taro SHIBATA

to the community

Biostatistics Division,

6. Talent development of all NCC staff members

Center for Research Administration and Support,

7. Recommending new initiatives and policy to the government

National Cancer Center

8. Contributing to global society in collaboration with internationalorganizations

CRAS:
Center for Research Administration and Support

Mission• To contribute to the providing best

CRAS
Office of Advanced Medical
Care Evaluation & HTA

Hospital
Hospital East
Research Institute
Exploratory Oncology
Research &Clinical Trial CenterCtr for Public Hearth Res
Ctr for Cancer Control& Info. Services2Mission & Activity of Biostatistics Div.

Organization of NCC
President

National Cancer Center

Biostatistics
Division

evidence and the improvement ofclinical practice and public health

7 full-timebiostatisticians*+ 1 grad. school
student

through the development andapplication of statistical methods.
Activity• Collaboration

Biostatistics Section
for each hosp.

• Consultation*) Includes 3 Trial Statisticians(責任試験統計家)
certified by The Biometric Society of Japan

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3• Training and education• Methodological Researchhttps://www.ncc.go.jp/en/cras/biostatistics/4

Examples of our activity• Collaboration, as a trial statistician

Dx: Drug, Rx: Radiotherapy, Sx: Surgery– JCOG Studies: Ongoing 101, in preparation 18– NCCH investigator-initiated clinical trials: Ongoing 8, inpreparation 8– EPOC Studies: Ongoing 5, in preparation 1– NCCHE investigator-initiated clinical trials: Ongoing 20, inpreparation 9(as of March 2017, includes ancillary studies of clinical trial,and IIT includes “Chiken”)• 136 consultations/FY2016 (not includes consultation activity
within above collaboration as a trial statistician)5

UMIN000001012

JCOG0705/KGCA01 (REGATTA trial)

Kunieda F., Nakamura K. et al., J Clin Oncol 29: 2011 (suppl; abstr e16554) .

JCOG1018 with NCCTG

6UMIN000008866

with KOREA
Fluoropyrimidine/Oxaliplatin

Gastrectomy (D1) plus
Unresectable GC
with single non-curable
factor (H1/P1/M1)(cT1-2, PS0-1, 20-75 years)

Colorectal Cancer
aged >=70
PS 0-2chemotherapy (S-1+CDDP)

R
Country
Institution
N0-1/N2-3
H1/P1/M1(mFOLFOX7 or XELOX) + BEVR
Fluoropyrimidine

Chemotherapy alone(5-FU/LV or Capecitabine) + BEV(S-1+CDDP)

 Primary endpoint in each country: PFS (n=380)

 Primary endpoint: OS Primary endpoint for combined analysis: OS (n=760)

 Planned accrual: n=330 (at least 110 pts from each country)

 Two data centers Two data centers, One primary analysis (publication)

Slide by Dr.Ken-ichi NAKAMURA @ NCCH (partially modified)

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 Two primary analyses (publications) followed by pre-plannedcombined analysis
7

Slide by Dr.Ken-ichi NAKAMURA @ NCCH (partially modified)

8

DREAM study with EORTC

UMIN000024890

UMIN000027280

JCOG1502C(J-BALLAD) with IRCI, NCI etc.

(EORTC-1527-GITCG-IG/JCOG 1609INT)
Unresectable Liver mets.
Colorectal Cancer
1st registaration
Chemotherapy
Evaluate confirmed DLMs* by DW-MRI* DLMs: Disappearing Liver Metastases

2nd registration, Liver resection
Pathological evaluation ofresidual tumor in resected DLMs
 Planned Accrual, 400 patients
 Accrual, 3 years
 Follow-up, 2 years

Study Chair Serge Evrard (Institut Bergonie, France)
 Manabu Shiozawa (Kanagawa Cancer Center)

Japanese trial -A Global
Study To Evaluate The
Potential Benefit of Adjuvant
Chemotherapy for SmallBowel Adenocarcinoma[小腸腺癌]

Participating sites
 Japan, 12 sites
 EU/US, 16 sites
Role of NCCH
 Liaison between Japan and EORTC HQ(Agreement, Site management, Study progress,Query assistance etc.）
 Project management on Japanese side
 Participation in the Steering Committee

 Primary endpoint: RFS (n=150)

Funding
 AMED (2016-) research fund on Japanese side

 Two data centers Two primary analyses (publications)followed by pre-planned combinedanalysis

 One data center One primary analysis (publication)
9Slide by Dr.Ken-ichi NAKAMURA @ NCCH (partially modified)

UMIN000030816/NCT03423199

NCCH1607 with Korea, Taiwan & Singapore

10Collaborative research with SWOG
－SWOG0124 and JCOG9511－

A Randomized, Double Blind, Placebo Controlled,
Phase 3 Trial for Hormone Receptor Positive, HER2
Negative Locoregionally Recurrent or Metastatic
Breast Cancer（NCCH1607, PATHWAY）• Combined analyses of safety data from twosimilar RCTs of– CDDP+VP16 vs CDDP+CPT-11 for ED-SCLC• To explorer the difference of AE/ADR between
two trials

Placebo+Tamoxifen +/- Goserelin
vsPalbociclib +Tamoxifen +/- Goserelin> Investigator initiated “Chiken”>

 Pfizer as a collaborator/sponsor
 One data center One primary analysis (publication)
11

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from Lara et al. ASCO2007 abstract#7524.
Lara et al. Cancer 116:5710-5715, 2010.

12

Methodological Projects with

Collaborative Research Activities

Foreign Investigators• Statistical methods in studying etiologic heterogeneity among disease subtypes– Motivated by large prospective cohort studies with retrieving tumor tissues fromincidence cancer patients• Specific activities:– Writing research papers together– Proposed and organized Invited Session in ENAR spring meeting– A cancer can be classified into subtypes by molecular and pathological features– Skype meeting as appropriate– Epidemiological research questions may be• a short catch-up, usually once a monthwhether disease subtypes have similar or distinct etiology?
which are the etiologically distinct subtypes?

• Preparation for submitting NIH grant application• e.g., smoking moderately increases the risk of overall CRC.
Some evidence shows that smoking may increase the risk of BRAF-mutated– Have formal subcontract agreement between PI’s institute (US) andCRC, but not be associated with BRAF wild-type CRC.

NCC

• Statistical issues include:• Including budget plan for the activities– Developing statistical models to address those questions– Study design consideration– Missing data problems on molecular data

etc…

13

14

15

http://www.eortc.org/blog/2018/02/01/european-and-japanese-clinical-research16
organisations-meet-to-collaborate-on-future-studies-in-cancer/

Collaboration between JCOG & EORTC(Evrard S et al. Ann Surg 2016)

http://www.eortc.org/c/news/(Kataoka K et al. JJCO2016)– SURCARE program (Surgical QC/QA program)– Exchange program for young investigators– JCOG-EORTC international symposium (Dec 2017)– New study concept discussed in gastric cancer & pathology
Slide by Dr.Ken-ichi NAKAMURA @ NCCH

無断転載・無断使用を禁じます。 UNAUTHORIZED COPYING AND REPLICATION ARE PROHIBITED.

UMIN000027552

MASTER KEY PROJECT(NCCH1612)

Moleculardiagnostic testing(TOP GEAR etc) Rare Cancer
Patients

Registrypart
May 2017-I.C.
Registration• Strength– Supportive environment, e.g. mind of clinicians, forbiostatisticians– Many clinical trials are ongoing or in-preparation

Review biomarkers– Experience of multi-modality, non-pharmaceutical clinical trials– Network of international collaboration

Assignment to mutation-based trials

Biomarker
A

Biomarker
B

Biomarker
C

Drug A
Phase II

Drug B
Phase II

Drug C
Phase II

Biomarker
Negative

Summary

Sub-study
partDrug X Drug Y
Phase II Phase II• Perspective– New framework for clinical trial, i.e. collaboration with basicscientists,

All pts
Follow-up

Slide by Dr.Ken-ichi NAKAMURA @ NCCH (partially modified)

無断転載・無断使用を禁じます。 UNAUTHORIZED COPYING AND REPLICATION ARE PROHIBITED.

informaticians, outreach specialists etc.
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