Target Therapy With GEMOX in Recectable Gallbladder Carcinoma Patients Monitored by ctDNA

Official title

A Multicentre, Open-label, Randomised, Controlled Study of Target Therapy Based on Tumor Molecular Profiling With GEMOX in Recectable Gallbladder Carcinoma Patients Monitored by ctDNA.

Overview

The purpose of this study is to evaluate the feasibility, efficacy and safety of target therapy according to genomic and proteomic profiling combined with GEMOX in recectable gallbladder carcinoma patients monitored by ctDNA.

Detailed description

Genomic profiling studies the deoxyribonucleic acid (DNA) of a tumor to detect genetic changes or abnormalities. immuno-histochemistry tests reveal the abnormal activation status of signal pathways involved in study. These information will be used to recommend target therapy which may be more likely to result in a beneficial response. Patients will receive target antitumor agents according to the result of genomic and proteomic profiling and be monitored by circulating tumor DNA(ctDNA).

Interventions

• Drug gemcitabine and oxaliplatin.
  GEMOX Conventional chemotherapy:gemcitabine and oxaliplatin.
• Drug Afatinib
  Target therapy Drug: afatinib

Primary outcome measures

• 3-year DFS [Time frame: up to 3 years]

Secondary outcome measures (1)

• 3-year OS [Time frame: up to 3 years]

Eligibility criteria

Inclusion criteria

• Chinese#
• Stable vital signs, ECOG:0-1;
• Patients have a diagnosis of resectable gallbladder carcinoma by histopathology or cytopathology after radical surgery.
• Adequate fresh tumor tissue for genome sequencing and immunohistochemistry test; harboring mutations or abnormal activation of erb-b2 receptor tyrosine kinase signal pathway components
• Life expectancy of more than 18 weeks;
• T stage≥ T2 or histopathological lymph node positive according to AJCC (8th edition) staging.
• Adequate hepatic, hematologic and renal functions(ALT≤5×upper limit of normal (ULN), AST≤5×ULN, the Child-Pugh classification for class A or B, white blood cells≥3×10\^9/L, neutrophils≥1.5×10\^9/L, platelets≥75×10\^9/L , hemoglobin ≥ 90g/L, creatinine clearance rate≥60ml/min;
• Volunteer for this study, have written informed consent and have good Patient compliance;
• Female patients of childbearing potential and their mates agree to avoid pregnancy.

Exclusion criteria

• Have received following treatment before this study: a. Anti-tumor molecular target therapy; anti-tumor chemotherapy in 6 months; b. lesions have been treated by irradiation; c. participate in other therapeutic or interventional clinical trials.
• History of other malignancies except carcinoma in-situ of uterine cervix, cured basal cell carcinoma of skin and other malignancies for more than 5 years;
• Have serious concurrent illness including, but not limited to uncontrolled congestive heart failure(NYHA classification grade III or IV), unstable angina pectoris, unstable cardiac arrhythmias, uncontrolled moderate or serious hypertension(systolic blood pressure >21.3 Kpa or diastolic blood pressure >13.3 Kpa);
• Have ongoing or active serious infection;
• Have uncontrolled diabetes mellitus;
• Psychiatric illness which potentially hamper the ability to willingly give written informed consent and compliance with the study protocol;
• Active autoimmune diseases require long-term use of steroids or received allotransplantation
• Other serious illness considered not suitable for this study by investigators.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

China · 2 centers

• Renji hospital, Shanghai Jiaotong University School of Medicine — Shanghai
• Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine — Shanghai

Publications

• Yang M, Zhao Y, Li Y, Cui X, Liu F, Wu W, Wang XA, Li M, Liu Y, Liu Y. Afatinib in combination with GEMOX chemotherapy as the adjuvant treatment in patients with ErbB pathway mutated, resectable gallbladder cancer: study protocol for a ctDNA-based, multicentre, open-label, randomised, controlled, phase II trial. BMJ Open. 2023 Feb 28;13(2):e061892. doi: 10.1136/bmjopen-2022-061892. PMID 36854604

Identifiers

NCT: NCT04183712 · LTGBCLYB2019

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗