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

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.

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.

Study Overview

• Status: Recruiting
• Conditions: Gallbladder Carcinoma
• Intervention / Treatment: Drug: gemcitabine and oxaliplatin.; Drug: Afatinib

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).

• Study Type: Interventional
• Enrollment (Anticipated): 102
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China
      • Recruiting
      • Renji Hospital, Shanghai Jiaotong University School of Medicine
    • Shanghai, Shanghai, China
      • Recruiting
      • Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 78 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Afatinib with GEMOX; Patients will receive targeted therapy(Afatinib 40mg orally from day 1 to day 21 combined with GEMOX chemotherapy(gemcitabine 1000 mg/m2 on days 1 and 8 of each cycle by IV infusion and oxaliplatin 100 mg/m2 on day 1 of each cycle by IV infusion)	Drug: gemcitabine and oxaliplatin.; GEMOX Conventional chemotherapy:gemcitabine and oxaliplatin.; Other Names: Gemzar(Eli Lilly and Company) and Aiheng(Jiangsu Hengrui Medicine Co., Ltd.); Drug: Afatinib; Target therapy Drug: afatinib; Other Names: Gilotrif(Boehringer-Ingelheim)
Active Comparator: GEMOX; Patients will receive conventional GEMOX chemotherapy (gemcitabine 1000 mg/m2 on days 1 and 8 of each cycle by IV infusion and oxaliplatin 100 mg/m2 on day 1 of each cycle by IV infusion）	Drug: gemcitabine and oxaliplatin.; GEMOX Conventional chemotherapy:gemcitabine and oxaliplatin.; Other Names: Gemzar(Eli Lilly and Company) and Aiheng(Jiangsu Hengrui Medicine Co., Ltd.)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
3-year DFS	3-year disease free survival rates:The progression is defined consistent with contrast enhanced MRI/CT.	up to 3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
3-year OS	3-year Overall survival rates	up to 3 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
sensitivity and specificity of ctDNA	sensitivity and specificity of ctDNA compared to clinical index（CA199，CEA）for monitoring tumour progression	up to 2 years

Collaborators and Investigators

• Sponsor: Shanghai Jiao Tong University School of Medicine
• Collaborators: Shanghai Zhongshan Hospital; RenJi Hospital; Ruijin Hospital

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2020
• Primary Completion (Anticipated): June 1, 2023
• Study Completion (Anticipated): December 1, 2023

Study Registration Dates

• First Submitted: November 28, 2019
• First Submitted That Met QC Criteria: December 2, 2019
• First Posted (Actual): December 3, 2019

Study Record Updates

• Last Update Posted (Actual): December 23, 2022
• Last Update Submitted That Met QC Criteria: December 21, 2022
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Digestive System Neoplasms; Gallbladder Diseases; Biliary Tract Diseases; Biliary Tract Neoplasms; Carcinoma; Gallbladder Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Protein Kinase Inhibitors; Gemcitabine; Oxaliplatin; Afatinib
• Other Study ID Numbers: LTGBCLYB2019

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No