UMIN-CTR Clinical Trial

Basic information
Public title	Biomarker analysis for alectinib and bevacizumab in ALK-positive NSCLC
Acronym	NLCTG1501-BM
Scientific Title	Biomarker analysis for alectinib and bevacizumab in ALK-positive NSCLC
Scientific Title:Acronym	NLCTG1501-BM
Region	Japan

Condition
Condition	ALK-positive non-small cell lung cancer
Classification by specialty	Pneumology
Classification by malignancy	Malignancy
Genomic information	YES

Objectives
Narrative objectives1	To determine the biomarker for the combination therapy of alectinib and bevacizumab in ALK-positive NSCLC.
Basic objectives2	Others
Basic objectives -Others	To determine the biomarker for the combination therapy of alectinib and bevacizumab in ALK-positive NSCLC, liquid biopsy will be performed.
Trial characteristics_1	Exploratory
Trial characteristics_2
Developmental phase	Not applicable

Assessment
Primary outcomes	To determine the biomarker for the combination therapy of alectinib and bevacizumab in ALK-positive NSCLC.
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	20 years-old <=
Age-upper limit	Not applicable
Gender	Male and Female
Key inclusion criteria	According to NLCTG1501
Key exclusion criteria	According to NLCTG1501
Target sample size	11

Research contact person
Name of lead principal investigator	1st name Toshoaki Middle name Last name Kikuchi
Organization	Niigata University Graduate School of Medical and Dental Sciences
Division name	Department of Respiratory Medicine and Infectious Diseases
Zip code	9518510
Address	1-757 Asahimachidori, Chuouku, Niigata, Japan
TEL	025-368-9325
Email	kikuchi@med.niigta-u.ac.jp

Public contact
Name of contact person	1st name Satoshi Middle name Last name Watanabe
Organization	Niigata University Graduate School of Medical and Dental Sciences
Division name	Department of Respiratory Medicine and Infectious Diseases
Zip code	9518510
Address	1-757 Asahimachidori, Chuouku, Niigata, Japan
TEL	025-368-9325
Homepage URL
Email	satoshi7@med.niigata-u.ac.jp

Sponsor
Institute	Niigata University
Institute
Department

Funding Source
Organization	Niigata University
Organization
Division
Category of Funding Organization	Self funding
Nationality of Funding Organization

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

IRB Contact (For public release)
Organization	Institutional Review Board of the Niigata University
Address	1-754 Asahimachidori, Chuouku, Niigata, Japan
Tel	025-2272625
Email	sanonao@adm.niigata-u.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	2018 Year 12 Month 08 Day

Related information
URL releasing protocol	N/A
Publication of results	Partially published

Result
URL related to results and publications	N/A
Number of participants that the trial has enrolled	12
Results	There was no difference in PFS or OS by serum biomarkers, but there was a trend toward longer PFS in patients with some biomarker positivity.
Results date posted	2021 Year 12 Month 10 Day
Results Delayed
Results Delay Reason
Date of the first journal publication of results
Baseline Characteristics	Twelve patients with a median age of 67 years (range, 30-77) were enrolled between July 2015 and September 2018. Ten patients were female, all patients had adenocarcinoma histology with advanced ALK-positive NSCLC which were determined by fluorescence in situ hybridization, immunohistochemistry and/or reverse transcription PCR. All patients had received alectinib and a half of patients had been treated with 3 or more regimens before enrollment. At the time of data cutoff, the median follow-up for OS was 13.7 months for all patients and 26.4 months for living patients.
Participant flow	Patients who participated in the NLCTG1501 study were enrolled in the study.
Adverse events	NA
Outcome measures	Potential biomarkers in the plasma proteins were evaluated at baseline, 6 weeks, 12 weeks after the initiation of the combination therapy and when disease progressed. Fresh blood samples (14 ml) were collected in EDTA tubes and centrifuged for 10 minutes at 1400 g at room temperature to separate plasma and buffy coats. All samples were stored at -80 C until the analysis. Cell free DNA (cfDNA) was subsequently extracted from the plasma using an AVENIO cfDNA isolation kit (Roche diagnostics, Mannheim, Germany). Sample plasma analysis was carried out for a panel of circulating angiogenesis and cytokines: angiopoietin-2, bone morphogenetic protein (BMP)-9, epidermal growth factor (EGF), endoglin, fibroblast growth factor (FGF)-1, placental growth factor (PLGF), granulocyte-colony stimulating factor (G-CSF), heparin-binding EGF-like growth factor (HB-EGF), endotherin-1, Hepatocyte Growth Factor (HGF), follistatin, leptin, VEGF-A, VEGF-C, VEGF-D using Bio-Plex 200 (Bio-Rad, Hercules, USA) and Human Angiogenesis/Growth Factor Magnetic Bead Panel (Merck Millipore, Burlington, USA). The circulating tumor DNA (ctDNA) samples were analyzed with NextSeq500 (Illumina, San Diego, USA) and AVENIO ctDNA Surveillance Kit , which can detect mutations in 197 genes (Roche Diagnostics).
Plan to share IPD
IPD sharing Plan description

Progress
Recruitment status	Completed
Date of protocol fixation	2015 Year 10 Month 15 Day
Date of IRB	2015 Year 11 Month 16 Day
Anticipated trial start date	2015 Year 10 Month 15 Day
Last follow-up date	2020 Year 11 Month 30 Day
Date of closure to data entry	2022 Year 12 Month 12 Day
Date trial data considered complete	2022 Year 12 Month 12 Day
Date analysis concluded	2023 Year 12 Month 31 Day

Other
Other related information	Evaluate tumor DNA and RNA from plasma of patients treated in NLCTG1501 trial.

Management information
Registered date	2018 Year 12 Month 08 Day
Last modified on	2022 Year 12 Month 12 Day

Link to view the page
URL(English)	https://center6.umin.ac.jp/cgi-open-bin/icdr_e/ctr_view.cgi?recptno=R000040096