Clinical trial NCT02610218: Liquid Biopsy in Monitoring the Therapeutic Efficacy of Targeted Therapy in Advanced/Metastatic Gastric Cancer
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Gastric Cancer
Keywords: Cell free DNA
Circulating tumor cell
Therapeutic efficacy
Lead sponsor: Peking University
Sponsor class: OTHER
First posted: 2015-11-20
Enrollment: 124
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Anticipated 124 patients with histologically confirmed HER2 positive advanced/metastatic gastric cancer

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Correlation of HER2 status on CTCs and cfDNA with clinical outcomes
timeFrame: through study completion, an average of 1 year
Secondary outcomes:
measure: Gene variations associated with resistance in HER2-targeted therapy
timeFrame: up to 6 months
Other outcomes:
Locations:
city: Beijing
country: China
facility: Department of GI Oncology, Peking University Cancer Hospital
state: Beijing
Study officials:
References: