Liquid Biopsy in Monitoring the Therapeutic Efficacy of Targeted Therapy in Advanced/Metastatic Gastric Cancer

Gastric Cancer Clinical Trial

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02610218
• Other study ID #: LiquidBiopsy
• Status: Active, not recruiting
• Phase: N/A
• First received: November 18, 2015
• Last updated: October 29, 2017
• Start date: April 2016
• Est. completion date: December 2018

Study information

• Verified date: October 2017
• Source: Peking University
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

To evaluate the clinical significance of cell free DNA (cfDNA) and circulating tumor cells (CTCs) in real-time monitoring the therapeutic response during HER2-targeted therapy in histologically confirmed HER2 positive advanced/metastatic gastric cancer.

Description:

The study is a single-center, prospective study undertaken in anticipated 124 patients with both histologically HER2 positive and negative advanced/metastatic gastric cancer. Peripheral blood samples of 12.5 mL were collected from the patients for cfDNA and CTCs analysis. The blood samples will be respectively drawn before therapy, at the time that the patients achieve the optimal response and when they suffer progressive disease. The enumeration of CTCs as well as the detection of HER2 expression will be achieved via the integrated subtraction enrichment (SET) and immunostaining-fluorescence in situ hybridization (iFISH) platform. Further, for the geneomic analysis, the enriched single CTC will be isolated for single-cell targeted sequencing. While for cfDNA analysis, extracted DNA from plasma will be directly subjected to targeted sequencing. The correlation of the HER2 status on CTCs and the HER2 amplification in cfDNA to the therapeutic response will be evaluated. Moreover, gene variations associated with resistance in HER2-targeted therapy will be also studied based on the genomic data from sequencing of CTC and cfDNA.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 124
• Est. completion date: December 2018
• Est. primary completion date: January 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Having signed informed consent

• Age= 18 years old

• Histologically confirmed HER2 positive gastric adenocarcinoma

• Unresectable recurrent or metastatic disease

• Measurable disease according to the RECIST criteria

• Karnofsky performance status =60

• Life expectancy of =2 month

• ALT and AST<2.5 times ULN (=5 times ULN in patients with liver metastases)

• Serum albumin level =3.0g/dL

• Serum AKP < 2.5 times ULN

• Serum creatinine <ULN, and CCr < 60ml/min

• Bilirubin level < 1.5 ULN

• WBC>3,000/mm3, absolute neutrophil count =2000/mm3, platelet>100,000/mm3, Hb>9g/dl

Exclusion Criteria:

• Brain metastasis (known or suspected)

• Surgery (excluding diagnostic biopsy) within 4 weeks prior to study entry. Contraindications of nuclear magnetic resonance image such as fitment of cardiac pacemaker , nerve stimulator, or aneurysm clip, and metallic foreign body in eye ball and so on.

• Allergic constitution or allergic history to protium biologic product or any investigating agents.

• Severe heart disease or such history as recorded congestive heart failure, uncontrolled cardiac arrhythmia, angina pectoris needing medication, cardiac valve disease, severe abnormal ECG findings, cardiac infarction , or retractable hypertension.

• Pregnancy or lactation period

• Other previous malignancy within 5 year, except non-melanoma skin cancer

• Pre-existing neuropathy>grade 1

• Legal incapacity

Related Conditions & MeSH terms

• Gastric Cancer
• Stomach Neoplasms

Intervention

Other:
• CTC and cfDNA analysis
The enumeration of CTCs as well as the detection of HER2 expression will be achieved via the integrated subtraction enrichment (SET) and immunostaining-fluorescence in situ hybridization (iFISH) platform. Further, for the geneomic analysis, the enriched single CTC will be isolated for single-cell targeted sequencing. While for cfDNA analysis, extracted DNA from plasma will be directly subjected to targeted sequencing. Tumor response evaluation will be performed after two cycles of chemotherapy by CT/MRI based on RECIST. Clinical data, including tumor stage, metastastic organ, chemotherapy regimen, objective response, progression free survival, overall survival, etc, will be collected according to study protocol.

Locations

Country	Name	City	State
China	Department of GI Oncology, Peking University Cancer Hospital	Beijing	Beijing

Sponsors (1)

Lead Sponsor	Collaborator
Peking University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Correlation of HER2 status on CTCs and cfDNA with clinical outcomes	To evaluate the correlation of CTCs and their HER2 expression status to the clinical outcomes	through study completion, an average of 1 year
Secondary	Gene variations associated with resistance in HER2-targeted therapy	To study the gene variations associated with resistance in HER2-targeted therapy based on the genomic data from sequencing of CTC and cfDNA	up to 6 months