Molecularly Target Therapy With GEMOX in Advanced or Recurrent Extrahepatic Cholangiocarcinoma and Gallbladder Carcinoma

A Multicentre, Open-label, Randomised, Controlled Study of Molecularly Precision Target Therapy Based on Tumor Molecular Profiling With GEMOX in Advanced or Recurrent Extrahepatic Cholangiocarcinoma and Gallbladder Carcinoma

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 advanced or recurrent extrahepatic cholangiocarcinoma and gallbladder carcinoma.

Study Overview

• Status: Unknown
• Conditions: Gallbladder Cancer; Cholangiocarcinoma of the Extrahepatic Bile Duct
• Intervention / Treatment: Drug: Cetuximab; Drug: Everolimus; Drug: Sorafenib; Drug: Trastuzumab; Drug: Lapatinib; Drug: Gefitinib; Procedure: biological test; Drug: GEMOX; Drug: Crizotinib

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 anti-tumor agents according to the result of genomic and proteomic profiling.

• Study Type: Interventional
• Enrollment (Anticipated): 152
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200092
      • Recruiting
      • Xinhua hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Chinese；
• Stable vital signs, KPS≥60;
• Patients have a diagnosis of advanced or recurrent metastatic extrahepatic cholangiocarcinoma or gallbladder carcinoma by histopathology or cytopathology, who are not suitable for radical surgery or have progressed R1 resection or palliative surgery;
• Adequate fresh tumor tissue for genome sequencing and immuno-histochemistry test; harboring mutations or abnormal activation of erb-b2 receptor tyrosine kinase signal pathway components;
• At least one measurable and evaluable site of disease according to the RECIST criteria version 1.1;
• Life expectancy of more than 12 weeks;
• Adequate hepatic, hematologic and renal functions(ALT≤10×upper limit of normal (ULN), AST≤10×ULN, the Child-Pugh classification for class A or B, white blood cells≥3×10^9/L, neutrophils≥1.5×10^9/L, platelets≥80×10^9/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:

  1. Anti-tumor molecular target therapy; anti-tumor chemotherapy in 6 months;
  2. lesions have been treated by irradiation;
  3. participate in other therapeutic or interventional clinical trials.
• Have central nervous system metastasis;
• 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 symptomatic ascites and need for treatment;

• Have serious concurrent illness including, but not limited to

  1. 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);
  2. ongoing or active serious infection;
  3. uncontrolled diabetes mellitus;
  4. psychiatric illness which potentially hamper the ability to willingly give written informed consent and compliance with the study protocol;
  5. HIV infection;
  6. other serious illness considered not suitable for this study by investigators.
• be allergic or have contraindications to target medicines involved in this study, gemcitabine or oxaliplatin.

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: target therapy; The patients wil receive conventional chemotherapy(GEMOX) combined with target agents according to the result of genomic and proteomic profiling of tumor tissue.	Drug: Cetuximab; Drug: Everolimus; Drug: Sorafenib; Drug: Trastuzumab; Drug: Lapatinib; Drug: Gefitinib; Procedure: biological test; mutation and signal pathway activation status analysis; Drug: GEMOX; Conventional chemotherapy:gemcitabine and oxaliplatin; Drug: Crizotinib
Other: GEMOX; The patients wil receive conventional chemotherapy(GEMOX).	Procedure: biological test; mutation and signal pathway activation status analysis; Drug: GEMOX; Conventional chemotherapy:gemcitabine and oxaliplatin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival	From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 1 year. The progression is defined consistent with Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria for solid tumors.	up to 1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival		up to 2 years
Objective Response Rate	Objective Response Rate is defined as the percentage of patients with a complete or partial response to treatment, consistent with RECIST version 1.1 criteria for solid tumors.	up to 1 year
Disease Control Rate	Disease Control Rate is defined as the percentage of patients with a complete or partial response to treatment or stable disease, consistent with RECIST version 1.1 criteria for solid tumors.	up to 1 year
percentage of patients with Clinical Benefit Response	Composite measure based on patient-reported pain (per Faces pain scale revised), patient-reported pain medication, Karnofsky performance status(KPS), and weight. Clinical benefit is indicated by either:(a) improvement in pain (less pain intensity with stable or decreased pain medication; or less pain medication with stable or decreased pain intensity) with stable or improved KPS; or (b) improvement in KPS with stable or improved pain.With stable for KPS and pain, clinical benefit may be indicated with an observation of positive weight change. Clinical benefit response (CBR) was classified weekly and a patient was considered a clinical benefit responder if clinical benefit was observed and maintained over a 4 week period.	up to 1 year

Collaborators and Investigators

• Sponsor: Shanghai Jiao Tong University School of Medicine
• Collaborators: RenJi Hospital; Huashan Hospital; Ruijin Hospital; Eastern Hepatobiliary Surgery Hospital; Xinhua Hospital, Shanghai Jiao Tong University School of Medicine
• Investigators: Principal Investigator: liu yingbin, PHD, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine

Study record dates

Study Major Dates

• Study Start: July 1, 2016
• Primary Completion (Anticipated): December 1, 2019
• Study Completion (Anticipated): December 1, 2020

Study Registration Dates

• First Submitted: July 13, 2016
• First Submitted That Met QC Criteria: July 14, 2016
• First Posted (Estimate): July 19, 2016

Study Record Updates

• Last Update Posted (Actual): May 7, 2018
• Last Update Submitted That Met QC Criteria: May 4, 2018
• Last Verified: May 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Digestive System Neoplasms; Gallbladder Diseases; Biliary Tract Diseases; Biliary Tract Neoplasms; Cholangiocarcinoma; Gallbladder Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Immunological; Protein Kinase Inhibitors; Trastuzumab; Sorafenib; Gefitinib; Everolimus; Cetuximab; Lapatinib; Crizotinib
• Other Study ID Numbers: DLY201507

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided