Molecular Evaluation of Neoadjuvant Chemotherapy for Locally Advanced Gastric Cancer

NCT03425058 | Completed

• 1 other identifier: 2017YJZ38
• Study Type: observational
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

Gastric cancer (GC) is a leading global health problem and is the third most common cause of cancer related death. Neoadjuvant chemoradiotherapy (nCRT) followed by surgery is the mainstay treatment for locally advanced gastric cancer, and variable degrees of tumor regression are observed after nCRT. Treatment strategies, including close surveillance without immediate surgery, have been investigated to spare patients with complete tumor regression from potentially adverse outcomes of radical surgery. However, clinical and radiological assessment of treatment response does not deliver an ideal accuracy of patients identification with complete response. In the present study, we focused on the clinical courses of patients who have developed locally advanced gastric cancer, and investigated the potential clinical utility of the detection of deficient MMR(dMMR), microsatellite instability(MSI) status and the decreasing level of circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA) as promising biomarkers for the diagnosis and prediction of GC during treatment progress. Twenty milliliters of plasma were collected at 3 time points: before nCRT; after 2 cycles of nCRT; and after surgery. Firefly ctDNA NGS assays were used to track ctDNA mutations previously characterized in paired tumor tissue by massively parallel sequencing (MPS). We investigated whether circulating tumor DNA (ctDNA) detection can reflect tumor response to nCRT and detect minimal residual disease(MRD) after surgery. We compared CTC and ctDNA levels to clinical, radiological and pathological assessment modalities for nCRT response. The results will provide lots of information which may contribute to promote the treatment of GC patients. We want to introduce these strategies into clinical practice if possible.

Conditions

Gastric Cancer

Keywords

Molecular Evaluation; Locally Advanced Gastric Cancer; Neoadjuvant Chemotherapy; ctDNA; CTC; dMMR/MSI

Outcome Measures

Primary Outcomes (2)

• The relationship between dMMR/MSI status and response to neoadjuvant chemotherapy

  The relationship between dMMR/MSI status and response to neoadjuvant chemotherapy

  November 22, 2017 to December 31, 2018

• The concordance and accuracy of response evaluation results determined by ctDNA, CTCs compared with imaging and serum tumor biomarkers(CEA, CA19-9,CA72-4 et al)

  The concordance and accuracy of response evaluation results determined by ctDNA, CTCs compared with imaging and serum tumor biomarkers(CEA, CA19-9,CA72-4 et al)

  November 22, 2017 to December 31, 2018

Secondary Outcomes (2)

• Prognostic values of the CTCs,ctDNA and dMMR/MSI testing

  November 22, 2017 to December 31, 2018

• The concordance of mutations in tumor tissue and ctDNA

  November 22, 2017 to December 31, 2018

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

locally advanced gastric cancer patients without distant metastasis or peritoneal dissemination defined as cTNM stage of T4a/T4bN+M0

You may qualify if:

• Ambulatory males or females, age ≥ 18 years
• Karnofsky Performance Score (KPS) ≥70% or ECOG performance status: 0 or 1
• Pathologically confirmed gastric adenocarcinoma (regardless of degree of histologic differentiation) or adenocarcinoma with signet-ring cell carcinoma , mucinous adenocarcinoma
• Clinical Preoperative Stage cT4a/T4bN+M0 disease, including T4b、Bulky-N2, confirmed by CT/EUS
• Adequate organ function as defined below: Hemoglobin ≥ 9 g/dl, Hematologic Absolute Neutrophil Count （ANC） ≥ 1.5\*109/L, Platelets ≥ 100\*109/L, Aspartate Aminotransferase（AST） and Alanine Aminotransferase(ALT)≤ 2.5×ULN, Alkaline pPosphatase( ALP) ≤ 2.5×ULN, Total Bilirubin （TBIL）≤ 1.5×ULN, Renal Serum Creatinine \< 1.5 ULN, Serum Albumin ≥ 30g/l.
• No serious concomitant disease that make survival period \< 5 years
• No pleural effusion, no ascites exceeding the pelvis and no metastasis to the peritoneum, liver or other distant organs are confirmed by abdominal pelvic CT.
• Planning to undergo gastric cancer D2 surgery after neoadjuvant chemotherapy
• No prior antitumor treatment is allowed, including chemotherapy, radiotherapy, immune therapy or target therapy
• No mechanical obstruction.
• Negative serum or urine pregnant test within 7 days prior to randomization for child-bearing age women
• Sexually active males or females willing to practice contraception during the study until 30 days after end of study.
• Subjects has to voluntarily join the study and sign the Informed Consent Form for the study

You may not qualify if:

• Female in pregnancy or lactation, or refuse to receive Contraception measures during chemotherapy
• With distant metastasis or peritoneal dissemination diagnosed by CT/EUS
• Underwent prior antitumor treatment, including chemotherapy, radiotherapy, immune therapy or target therapy
• Serious uncontrolled intercurrent infections or other serious uncontrolled concomitant disease or condition that would make the subject inappropriate for study participation or any serious medical disorder that would interfere with the subject's safety (including current active hepatic, biliary, renal, respiratory disease, uncontrolled diabetes hypertension et al)
• Clinically serious cardiac disease or pulmonary dysfunction.
• Patients require emergency surgery with complications (bleeding, perforation and obstruction) caused by gastric cancer
• Other complications that cause no radical resection
• Serious concomitant disease that make survival period \< 5 years
• No detection of CTCs or ctDNA in peripheral blood samples before NCT be enrolled in other clinical trials
• Allergic reaction to S-1 or oxaliplatin
• Abnormal GI tract function
• Refuse to provide blood/tissue sample
• Sexually active males or females refuse to practice contraception during the study until 30 days after end of study.
• Person with no capacity (legally) or inappropriate to continue study treatment for ethics/medical reasons.
• Other situation to be judged not adaptive to the study by investigators

Sponsors & Collaborators

• Peking University Cancer Hospital & Institute: lead

Study Sites (1)

Beijing Cancer Hospital

Beijing, Beijing Municipality, 10000, China

Location

Biospecimen

Retention: SAMPLES WITH DNA

blood samples; formalin-fixed, paraffin-embedded tumor blocks

MeSH Terms

Conditions

Stomach Neoplasms

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases

Study Officials

• Jiafu Ji, MD

  Peking University Cancer Hospital & Institute

  STUDY CHAIR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: February 1, 2018
• First Posted: February 7, 2018
• Study Start: November 22, 2017
• Primary Completion: February 1, 2020
• Study Completion: October 1, 2021
• Last Updated: August 9, 2022

Record last verified: 2022-08

Locations

CN (1)