UMIN-CTR Clinical Trial

Public title

Circulating Tumor DNA Sequencing Study for Rare Cancers: an Ancillary Research Study to the MASTER KEY Registry Study (NCCH1612)

Acronym

Circulating Tumor DNA Sequencing Study for Rare Cancers

Scientific Title

Circulating Tumor DNA Sequencing Study for Rare Cancers: an Ancillary Research Study to the MASTER KEY Registry Study (NCCH1612)

Scientific Title:Acronym

Circulating Tumor DNA Sequencing Study for Rare Cancers

Region

Japan

Condition

Rare cancers, Rare hisotogical subtypes of major cancers, Carcinoma of unknown primary

Classification by specialty

Hematology and clinical oncology

Gastrointestinal surgery

Classification by malignancy

Malignancy

Genomic information

YES

Narrative objectives1

1) To analyze the types and incidence of genetic alterations in rare cancer (solid tumor) patients using circulating tumor DNA (ctDNA) next generation sequencing (NGS) analysis.
2) To analyze the cancer specific gene alterations, treatment details according to each gene alteration, treatment outcome, etc., by integrating the MASTER KEY Registry study (NCCH1612) clinicopathological data and the genetic information gained from this research study.

Basic objectives2

Others

Basic objectives -Others

Analyze the clinical utility of Guardant360 gene panel for ctDNA in rare cancers.

Trial characteristics_1

Exploratory

Trial characteristics_2

Developmental phase

Not applicable

Primary outcomes

1) Overall incidence of any genetic alterations(analyzed in all rare cancer patients cohort and in each histopathlological subgroup cohort)
2) Incidence of individual genetic alteration(analyzed in all rare cancer patients cohort and in each histopathlological subgroup cohort)

Key secondary outcomes

To investigate the congruence of the reported gene alterations from this research study and tissue-based NGS from prior tests, treatment patterns according to each gene alteration, response to treatment, etc.

Study type

Observational

Basic design

Randomization

Randomization unit

Blinding

Control

Stratification

Dynamic allocation

Institution consideration

Blocking

Concealment

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

Age-lower limit

16

years-old

<=

Age-upper limit

Not applicable

Gender

Male and Female

Key inclusion criteria

1) Patients aged 16 years or older at registration.
2) Patients who meet the eligible criteria for the MASTER KEY Registry study (NCCH1612) and have provided a written consent to the MASTER KEY Registry study (NCCH1612). (Enrollment into the MASTER KEY Registry study (NCCH1612) must be done before enrollment into this research study.
3) Patients who provided a written consent to participate in the study (for patients less than 20 years of age, their legally acceptable representative must give consent). For patients who have a will to consent but are physically unable to provide a signature, an allograph by a relative is applicable.

Key exclusion criteria

none

Target sample size

100

Name of lead principal investigator

1st name	Noboru
Middle name
Last name	Yamamoto

Organization

National Cancer Center Hospital

Division name

Department of Experimental Therapeutics

Zip code

113-0033

Address

5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan

TEL

03-3542-2511

Email

nbryamam@ncc.go.jp

Name of contact person

1st name	Hitomi
Middle name
Last name	Okuma

Organization

National Cancer Center Hospital

Division name

Clinical Trial Management Section, Research Management Division/Department of Breast and Medical Onc

Zip code

113-0033

Address

5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan

TEL

03-3542-2511

Homepage URL

Email

hsumiyos@ncc.go.jp

Institute

National Cancer Center Hospital

Institute

Department

Personal name

Organization

Medical Affairs Japan/Asia
Guardant Health Inc

Organization

Division

Category of Funding Organization

Profit organization

Nationality of Funding Organization

USA

Co-sponsor

Name of secondary funder(s)

Organization

National Cancer Center Institutional Review Board

Address

5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan

Tel

03-3542-2511

Email

NCC_IRBoffice@ml.res.ncc.go.jp

Secondary IDs

NO

Study ID_1

Org. issuing International ID_1

Study ID_2

Org. issuing International ID_2

IND to MHLW

Institutions

国立がん研究センター中央病院

Date of disclosure of the study information

2018

Year

10

Month

22

Day

URL releasing protocol

https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2021.732525/full

Publication of results

Published

URL related to results and publications

https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2021.732525/full

Number of participants that the trial has enrolled

100

Results

Ninety-eight patients were analyzed. Mean turn-around-time for results was 9.5 days. Seventy-six patients had detectable gene alterations in plasma, with a median of 2.8 alterations/patient. Five received matched-therapy based on plasma NGS results. Two developed known resistance mutations while on targeted therapy. Patients with an alteration having VAF 5% and over had a significantly shorter survival compared to those of lower VAF.

Results date posted

2023

Year

10

Month

16

Day

Results Delayed

Results Delay Reason

Date of the first journal publication of results

Baseline Characteristics

Plasma NGS tests were performed on patients 16 years or older with advanced/metastatic rare solid tumors who matched the criteria for the MASTER KEY Project and who provided written consent for plasma NGS testing between November 2018 to January 2019. The number of prior therapies was not restricted, allowing both pharmacotherapy naive and pharmacotherapy-treated patients to be included. Blood was collected prior to initial pharmacotherapy, at the time of disease progression, or while on treatment. Rare cancer was defined as cancer with an annual incidence less than/or 6/100,000 population in Japan. Clinical data were obtained from the patients electronic medical records. Among the patients who underwent plasma testing, those with available archival formalin-fixed paraffin-embedded tumor tissue specimens collected within six months of blood draw were also tested with tissue NGS. The primary endpoint of the study was the alteration detection rate by plasma NGS testing. Secondary endpoints included the congruence of the reported gene alterations between plasma NGS and tissue NGS testing, application of relevant treatment according to the alterations, response to treatment, and survival. This study was approved by the National Cancer Center Institutional Review Board and was conducted in full concordance with the principles of the Declaration of Helsinki.

Participant flow

NGS assay of plasma DNA was carried out using Guardant360 (Guardant Health, Inc, Redwood City, CA). Cell-free DNA was isolated from plasma of patients blood samples. Guardant360 is a targeted, hybrid-capture-based NGS panel test which, at the time of the study, detected point mutations in 73 genes, insertion-deletion mutations (indels) in 23 genes, amplifications for 18 genes, and fusions of six genes (Supplementary Figure S1). Detailed protocols for DNA isolation, sequencing and data analysis have been reported (5). The detected gene alterations were then classified according to their actionable levels. Actionability was predicted based on potential sensitivity/resistance to either an approved targeted agent or an experimental targeted agent currently in clinical trials. Evidence levels were added to each gene alteration according to Clinical Practice Guidance for Next Generation Sequencing in Cancer Diagnosis and Treatment (6) using cancer genome knowledge databases, such as CanDL (https://candl.osu.edu/browse), Cancer Genome Interpreter (https://www.cancergenomeinterpreter.org/biomarkers), CIViC (https://civic.genome.wustl.edu/home), and OncoKB (https://www.oncokb.org/). The following levels of evidence were assigned to each gene alteration: level 1A, a Pharmaceuticals and Medical Devices Agency (PMDA)-approved biomarker for the tumor type; 1B, a United States FDA-approved biomarker for the tumor type (not approved by the PMDA) or a biomarker verified by a prospective molecularly driven clinical trial; 2A, a biomarker identified by subgroup analysis in a prospective clinical trial; 2B, an approved biomarker for a different tumor type or a biomarker with evidence supporting its clinical utility; 3A, a biomarker with evidence of proof-of-concept in at least one case report; 3B, a biomarker with evidence obtained from in vitro/in vivo experiments; and 4, other gene mutations in cancer. In the present study, gene alterations with evidence levels 1A-3A were judged as actionable for drug selection.

Adverse events

Not applicable

Outcome measures

Response to treatment was assessed according to version 1.1 of the Response Evaluation Criteria in Solid Tumor. Survival analyses were defined by the time interval from the date of blood sample extraction to the date of the relevant event. For Overall Survival (OS), qualifying events were death or loss of follow-up. For Progression Free Survival (PFS), the event date was the earliest of the date of discontinuation of therapy, the date of disease progression, or the last known date of clinical contact

Plan to share IPD

IPD sharing Plan description

Recruitment status

Completed

Date of protocol fixation

2018

Year

09

Month

21

Day

Date of IRB

2018

Year

10

Month

25

Day

Anticipated trial start date

2018

Year

11

Month

05

Day

Last follow-up date

2019

Year

11

Month

05

Day

Date of closure to data entry

Date trial data considered complete

Date analysis concluded

Other related information

Blood samples from rare cancer patients will be collected and tested by Guardant Health, Inc. gene panel to analyse the types and incidence of genetic alterations in rare cancer (solid tumor) patients. The genetic alteration results will also be integrated with the MASTER KEY Registry study (NCCH1612) clinicopathological data to further analyze the cancer specific gene alteration rate, etc.

Registered date

2018

Year

10

Month

05

Day

Last modified on

2023

Year

10

Month

16

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000039210