A Clinical Study of a Preoperative Translational Therapy for Unresectable Gallbladder Cancer

Study Overview
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Brief Summary
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This is an open-label,multicenter ,non-randomized,single arm exploratory study. The objective of this study is to evaluate the efficacy and safety of PD-1 antibody plus GEMOX as preoperative translational therapy for unresectable gallbladder cancer.

Detailed Description
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The aim of this study was to evaluate the efficacy and safety of carrilizumab in combination with gemcitabine and oxaliplatin (GEMOX) as a preoperative conversion therapy for unresectable gallbladder cancer. Patients with unresectable gallbladder cancer were enrolled to receive gemcitabine 1000 mg/m2 D1, D8 + oxaliplatin 100 mg/m2, D1 + carrilizumab 200 mg, D1, in 21-day cycles for 6-8 cycles, with changes in serum tumor parameters assessed at each course and abdominal CTA performed every two courses.The above treatment was terminated if the CT evaluation revealed disease progression, and the investigator could adjust the treatment regimen according to the guideline. The primary outcome measure of this study is the tumor radical resection rate; secondary outcome measure are objective response rate, disease control rate, progression-free survival, and overall survival. The safety indicators are the incidence and severity of adverse events (AE) and serious adverse events (SAE) according to NCI-CTCAEv5.0 criteria. Thirty-seven cases are expected to be enrolled in this study.

Official Title
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A Single-arm, Multicenter, Phase II Clinical Study of the Efficacy and Safety of Carrilizumab Combinated With Gemcitabine and Oxaliplatin (GEMOX) as a Preoperative Translational Therapy for Unresectable Gallbladder Cancer

Conditions
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Unresectable Gallbladder Cancer

Intervention / Treatment
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* Drug: Carrilizumab plus GEMOX


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The patient must sign an informed consent form; Age 18-75 years old, both male and female; ECOG performance status score (PS score) 0 or 1 point; Child-Pugh score A period; Patients with advanced or recurrent metastatic gallbladder cancer who are not suitable for radical surgery (R0), or non-radical surgery (R1), or palliative surgery, as confirmed by pathological histology or cytology. Have not received any systemic treatment within 6 months; The functional indicators of important organs meet the following requirements (1)Neutrophils≥1.5*109/L; platelets≥100*109/L; hemoglobin≥9g/dl; serum albumin≥3g/dl; (2)Thyroid-stimulating hormone (TSH) ≤ 2 times the upper limit of normal, and T3 and T4 are in the normal range; (3)Bilirubin ≤ 1.5 times the upper limit of normal; ALT and AST ≤ 3 times the upper limit of normal; (4)Serum creatinine ≤ 1.5 times the upper limit of normal, and creatinine clearance ≥ 60ml/min (calculated by Cockcroft-Gault formula); The subject has at least 1 measurable lesion (according to RECIST1.1); For women who are not breastfeeding or pregnant, use contraception during treatment or 12 months after the end of treatment. Exclusion Criteria: Past or simultaneous suffering from other malignant tumors, except for fully treated non-melanoma skin cancer, cervical carcinoma in situ, and thyroid papillary carcinoma; Have used gemcitabine-based chemotherapy or have used PD-1 monoclonal antibody or PD-L1 monoclonal antibody treatment within 6 months; Severe cardiopulmonary and renal dysfunction; Hypertension that is difficult to control with drugs (systolic blood pressure (BP) ≥140 mmHg and/or diastolic blood pressure ≥90mmHg) (based on the average of ≥3 BP readings obtained by ≥2 measurements); Abnormal coagulation function (PT>14s), have bleeding tendency or are receiving thrombolysis or anticoagulation therapy; After antiviral treatment, HBV DNA>2000 copies/ml, HCV RNA>1000; A history of esophageal and gastric varices, significant clinically significant bleeding symptoms or a clear tendency to appear within 3 months before enrollment; Active infections requiring systemic treatment; patients with active tuberculosis infection within 1 year before enrollment; a history of active tuberculosis infection more than 1 year before enrollment, and no formal anti-tuberculosis treatment or tuberculosis Still in the active period; Human immunodeficiency virus (HIV, HIV1/2 antibody) positive; A history of psychotropic drug abuse, alcohol or drug abuse; Known to have a history of severe allergies to any monoclonal antibodies, platinum drugs, or gemcitabine; Other factors judged by the investigator may affect the safety of the subjects or the compliance of the trial. Such as serious diseases (including mental illness) that require combined treatment, serious laboratory abnormalities, or other family or social factors.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: Carrilizumab plus GEMOX<br>Carrilizumab combinated With gemcitabine and oxaliplatin (GEMOX) | Drug: Carrilizumab plus GEMOX<br>* PD-1 antibody，200mg，D1，intravenous infusion, the administration time is 60 (+15) minutes. GEMOX chemotherapy : gemcitabine 1000mg/m2,D1，D8；oxaliplatin 100mg/m2,D1intravenous infusion.Three weeks is a course of treatment.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Radical resection rate | The proportion of patients whose tumors converted to a surgically resectable state and achieved radical resection within 8 courses of medication in all patients enrolled. | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate (ORR) | Complete response (CR) and partial response (PR), at 6 months by RECIST v.1.1 | 6 months | 
| Disease control rate(DCR) | Complete response (CR) ,partial response (PR) and stable disease, SD, at 6 months by RECIST v.1.1 | 6 months | 
| Progression-free survival (PFS) | The time from first drug administration to the first documented disease progression according to RECIST version 1.1 or to death from any cause, whichever occurred first. | 6 months | 
| Overall survival(OS) | The time from first drug administration to death from any cause. | 6 months | 
| The incidence of treatment-related adverse event | Percentage of participants who experienced treatment-related adverse event | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PD-1；GEMOX；Unresectable gallbladder cancer.