UMIN-CTR Clinical Trial

Public title

A prospective multicenter study for evaluation of the accuracy and clinical usefulness of the high-sensitivity next-generation sequencing panel using cytological specimens from lung cancer

Acronym

cPANEL trial

Scientific Title

A prospective multicenter study for evaluation of the accuracy and clinical usefulness of the high-sensitivity next-generation sequencing panel using cytological specimens from lung cancer

Scientific Title:Acronym

cPANEL trial

Region

Japan

Condition

lung cancer

Classification by specialty

Pneumology

Classification by malignancy

Malignancy

Genomic information

YES

Narrative objectives1

In this multicenter phase3 research, we evaluated the success rate of high-sensitivity multigene NGS panel tests using cytology specimens of lung cancer patients compared with the conventional gold-standard method (using tissue sample) at a 90% success rate, the concordance rate with companion diagnostic results by insurance medical treatment, and the number of days for reporting test results (turn around time; TAT), verify the feasibility in clinical practice.

Basic objectives2

Others

Basic objectives -Others

We exploratory investigate the nucleic acid yield (DNA and RNA), DNA-integrated number (DIN), and RNA-integrated number (RIN) for each cytology specimen collection method. Additionally, in cases where genetic mutations will be detected, the VAF concordance rate based on the LCCP between cytology specimens and FFPE tissue biopsy samples will be analyzed.

Trial characteristics_1

Confirmatory

Trial characteristics_2

Developmental phase

Phase III

Primary outcomes

The primary endpoint was to confirm the superiority of the high-sensitivity multigene NGS panel using cytology specimens compared with the conventional gold-standard method at a 90% success rate

Key secondary outcomes

1) Comparison of positive concordance rate and positive predictive value of gene mutation of "companion diagnostic test" and "high-sensitivity lung cancer multi-gene NGS panel test" for cytological specimens

2) Detection rate of gene abnormalities of 8 lung cancer-related genes (EGFR, BRAF, ALK, ROS1, MET, RET, KRAS, HER2) by "high-sensitivity lung cancer multi-gene NGS panel test" for cytological specimens

3) Number of days for reporting test results of "High-sensitivity lung cancer multigene NGS panel test" for cytological specimens

Study type

Interventional

Basic design

Single arm

Randomization

Non-randomized

Randomization unit

Blinding

Open -no one is blinded

Control

Self control

Stratification

Dynamic allocation

Institution consideration

Blocking

Concealment

No. of arms

1

Purpose of intervention

Diagnosis

Type of intervention

Maneuver

Interventions/Control_1

Cytology specimens (brushing cytology, needle aspiration washing solution, and pleural effusion) will be collected and stored in a nucleic acid stabilizer during examination or after procedure.

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) Patients who are suspected of having lung cancer (lung adenocarcinoma) and require cytology or histological diagnosis.
2) Patients over 20 years old.
3) Patients for whom the subject has given written consent to participate.

Key exclusion criteria

Exclusion criteria (primary registration)
1) Patients whom the principal investigator (physician) or sub investigator (physician) determines to be inappropriate to participate in this study.

Exclusion criteria (secondary registration)
1) If the lesion is a benign disease (organizing pneumonia, infection, etc.)
2) When malignant disease is suspected but no malignant cells are detected in a paired cytology specimen
3) If it was a metastatic lung tumor (e.g., lymphoma, gastrointestinal cancer, breast cancer lung metastasis)

Target sample size

260

Name of lead principal investigator

1st name	Kei
Middle name
Last name	Morikawa

Organization

St. Marianna University School of Medicine

Division name

Division of Respiratory Diseases, Department of Internal Medicine

Zip code

216-8511

Address

Miyamae-ku Sugao 2-16-1

TEL

+81449778111

Email

mokke@marianna-u.ac.jp

Name of contact person

1st name	Kei
Middle name
Last name	Morikawa

Organization

St. Marianna University School of Medicine

Division name

Division of Respiratory Diseases, Department of Internal Medicine

Zip code

216-8511

Address

Miyamae-ku Sugao 2-16-1

TEL

+81449778111

Homepage URL

Email

mokke@marianna-u.ac.jp

Institute

St. Marianna University School of Medicine

Institute

Department

Personal name

Organization

DNA Chip Research Inc.

Organization

Division

Category of Funding Organization

Other

Nationality of Funding Organization

Co-sponsor

Name of secondary funder(s)

Organization

St. Marianna University School of Medicine

Address

Miyamae-ku Sugao 2-16-1

Tel

+81449778111

Email

mokke@marianna-u.ac.jp

Secondary IDs

YES

Study ID_1

Clinical trial number #5532

Org. issuing International ID_1

St. Marianna University

Study ID_2

Org. issuing International ID_2

IND to MHLW

Institutions

Division of Respiratory Diseases, Department of Internal Medicine, St. Marianna University School of Medicine, Japan.
Department of Respiratory Medicine, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Japan
Department of Respiratory Medicine, National Hospital Organization Nagoya Medical Center, Japan
Department of Respiratory Medicine, Gifu Prefectural General Medical Center, Japan
Department of Thoracic Oncology, Kanagawa Cancer Center, Japan
Department of Respiratory Medicine, Kawasaki Medical School, Japan
Department of Respiratory Medicine, Kumamoto Regional Medical Center, Japan
Department of Pathology, Kanagawa Cancer Center, Japan

Date of disclosure of the study information

2022

Year

03

Month

18

Day

URL releasing protocol

Publication of results

Published

URL related to results and publications

Number of participants that the trial has enrolled

320

Results

For the primary endpoint, the success rate of LCCP genetic alteration testing for all eight genes using cytology specimens was 98.4%, showing superiority over the 90% success rate of conventional NGS panel tests. For the secondary endpoint, the positive concordance and predictive rates of the LCCP were 97.4% and 93.8, respectively, for patients with using conventional CDx tests.

Results date posted

2024

Year

05

Month

30

Day

Results Delayed

Results Delay Reason

Date of the first journal publication of results

Baseline Characteristics

The median age was 70 years, and 158 patients were male. There were 33 (13.3%), 25 (10.1%), 57 (23.0%), 132 (53.2%), and 1 (0.4%) clinical stage I, II, III, IV, and unknown cases, respectively. The numbers of histological diagnoses for adenocarcinoma, squamous cell carcinoma, small cell carcinoma, and non-specified cases were 153 (61.7%), 42 (16.9%), 28 (11.3%), and 25 (10.1%), respectively. The numbers of cytology specimens collected under guided transbronchial brushing (TBB)/TBNA/US or CT-guided puncture/pleural effusion/other procedures were 133 (53.6%), 56 (22.6%), 32 (12.9%), 20 (8.1%), and 7 (2.8%), respectively.

Participant flow

Adverse events

All tests at the time of diagnosis are covered by insurance, and in the event of an adverse event, appropriate measures will be taken immediately using health insurance and documented in the medical record, just as in routine medical care. No specific adverse health effects are anticipated as a result of participation in this study.

Outcome measures

The primary endpoint was to confirm the superiority of the LCCP using cytology specimens compared with the conventional gold-standard method at a 90% success rate, which was based on the average upper limit of the 95% confidence interval (CI) of 88.1% for multiple conventional panel tests using tissue specimens.
Success rates were defined as the extraction of 10 ng or more nucleic acids for both DNA and RNA and NGS analysis reads of over 5,000 for the DNA diagnostic module, over 2,000 for the DNA research module, and over 300 for the internal standard gene HPRT1 in the RNA module. Secondary endpoints included the LCCP-based detection of genetic abnormalities in eight lung cancer-related genes, EGFR, BRAF, ALK, ROS1, MET, RET, KRAS, and HER2; positive concordance rates between the LCCP and companion diagnostic tests; and reduced turnaround time for test results using LCCP cytology specimens. The exploratory endpoints included the nucleic acid yield (DNA and RNA), DNA-integrated number (DIN), and RNA-integrated number (RIN) for each cytology specimen collection method. Additionally, in cases where genetic mutations were detected, the VAF concordance rate based on the LCCP between cytology specimens and FFPE tissue biopsy samples was analyzed.

Plan to share IPD

IPD sharing Plan description

Recruitment status

Main results already published

Date of protocol fixation

2022

Year

02

Month

01

Day

Date of IRB

2022

Year

03

Month

09

Day

Anticipated trial start date

2022

Year

03

Month

18

Day

Last follow-up date

2023

Year

10

Month

11

Day

Date of closure to data entry

2023

Year

10

Month

11

Day

Date trial data considered complete

2023

Year

10

Month

11

Day

Date analysis concluded

2023

Year

10

Month

12

Day

Other related information

Registered date

2022

Year

03

Month

18

Day

Last modified on

2024

Year

05

Month

30

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000053766