Chemothetapy FORFIRINOX in Advanced or Recurrent Extrahepatic Cholangiocarcinoma and Gallbladder Carcinoma

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the feasibility, efficacy and safety of FORFIRINOX in advanced or recurrent extrahepatic cholangiocarcinoma and gallbladder carcinoma.

Detailed Description
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The purpose of this study is to evaluate the feasibility, efficacy and safety of FORFIRINOX in advanced or recurrent extrahepatic cholangiocarcinoma and gallbladder carcinoma.

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

Conditions
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Cholangiocarcinoma of the Extrahepatic Bile Duct, Gallbladder Cancer

Intervention / Treatment
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* Biological: mutation and signal pathway activation status analysis Drug: FORFIRINOX


Participation Criteria
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Eligibility Criteria
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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: Anti-tumor molecular target therapy; anti-tumor chemotherapy in 6 months; lesions have been treated by irradiation; participate in other therapeutic or interventional clinical trials. - Page 5 of 5 [DRAFT] - 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 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); ongoing or active serious infection; uncontrolled diabetes mellitus; psychiatric illness which potentially hamper the ability to willingly give written informed consent and compliance with the study protocol; HIV infection; 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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Chemotherapy<br>The patients wil receive conventional chemotherapy FORFIRINOX | Biological: mutation and signal pathway activation status analysis Drug: FORFIRINOX<br>* Conventional chemotherapy:5FU plus irinote- can plus oxaliplatin combination therapy<br>|

What is the study measuring?
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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 |