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Study design: Prospective, single-arm, single-center phase II clinical study; Primary endpoint: Objective response rate via investigator, Safety; Secondary endpoints: disease control rate, disease-free survival, overall survival, and proportion of acceptable radical resection of primary lesions; Main characteristics of enrolled patients: Patients with initially unresectable gallbladder cancer; Interventions: Combination of Gemcitabine, Nab-paclitaxel, Sintilimab and Bevacizumab; Sample size: Using Simon's two-stage design, 15 patients in the first stage, and if more than 4pts response, enlarge the sample size to 45 patients in total; Treatment until: 1. successfully conversed to resectable disease 2. progressed disease 3. intolerable toxicity 4. patient requests withdrawal; Research process: In this study, patients who met the inclusion criteria were evaluated at the end of every 9 weeks of treatment, up to surgical treatment or disease progression; Safety evaluation: Evaluate adverse reactions according to CTCAE 5.0; Follow up: every 90 days (±7 days) until the subject died, lost follow-up or the end of the study.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| combined treatment group | Experimental | Combination of Gemcitabine, Nab-paclitaxel, Sintilimab and Bevacizumab GC regimen: up to the results of safety run-in stage
Sintilimab: 200mg, iv, d1, q3w Bevacizumab: 7.5mg/kg, d1, q3w |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Combination of Gemcitabine, Nab-paclitaxel, Sintilimab and Bevacizumab | Drug | Combination of Gemcitabine, Nab-paclitaxel, Sintilimab and Bevacizumab |
|
| Measure | Description | Time Frame |
|---|---|---|
| objective response rate | objective response rate | 9 weeks |
| Safety:the incidence of adverse events and serious adverse events | Incidence of adverse events and serious adverse events | 3 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| disease control rate | disease control rate | 3 weeks |
| progress-free survival | progress-free survival | 3 weeks |
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Inclusion Criteria:
1. Before the implementation of any trial-related procedures, sign a written informed consent 2. Male or female ≥18 years old, ≤75 years old 3. Gallbladder carcinoma confirmed by histology or cytology 4. No previous systemic anti-tumor therapy (radiotherapy, chemotherapy, targeted or immunotherapy, etc.) 5. Expected survival time > 3 months 6. At least 1 measurable lesion according to RECIST1.1 criteria 7. ECOG PS score of 0-1 8. Sufficient organ function, the subject needs to meet the following laboratory indicators:
Exclusion Criteria:
Note: Hepatitis B subjects who meet the following criteria can also be enrolled:
1) Resting ECG has significant abnormalities in rhythm, conduction or morphology, and the symptoms are severe and uncontrollable, such as complete left bundle branch block, heart block above second degree, ventricular arrhythmia or with fast ventricular rate atrial fibrillation 2) Unstable angina, congestive heart failure, New York Heart Association (NYHA) grade ≥ 2 chronic heart failure 3) Any arterial thrombosis, embolism or ischemia occurred within 6 months before the selected treatment, such as myocardial infarction, unstable angina, cerebrovascular accident or transient ischemic attack, etc.; 4) Received major surgical operations (craniotomy, thoracotomy or laparotomy) or unhealed wounds, ulcers or fractures within 4 weeks before the first administration. Received tissue biopsy or other minor surgical procedures within 7 days before the first dose, except for venipuncture for intravenous infusion 5) Unsatisfactory blood pressure control (systolic blood pressure > 140 mmHg and/or diastolic blood pressure > 90 mmHg) 6) Active tuberculosis 7) Active or uncontrolled infection requiring systemic therapy 8) Clinically active diverticulitis, abdominal abscess, gastrointestinal obstruction 9) Liver disease such as cirrhosis, decompensated liver disease, acute or chronic active hepatitis 10) Poorly controlled diabetes (fasting blood glucose (FBG) > 10mmol/L) 11) Urine routine prompts urine protein ≥ ++, and confirmed 24-hour urine protein quantity > 1.0 g; 12) Patients with mental disorders who cannot cooperate with treatment 26. Medical history or disease evidence that may interfere with the test results, prevent the subject from participating in the whole study, abnormal treatment or laboratory test values, or other situations that the investigator believes are not suitable for enrollment. The investigator believes that there are other potential risks t
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Lu Wang | Contact | +86-18121299357 | w.lr@hotmail.com |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Fudan University Shanghai Cancer Center | Recruiting | Shanghai | 200032 | China |
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| overall survival | overall survival | 3 weeks |
| Proportion of acceptable radical resection of primary lesions | Proportion of acceptable radical resection of primary lesions | 3 weeks |
| ID | Term |
|---|---|
| D005706 | Gallbladder Neoplasms |
| ID | Term |
|---|---|
| D001661 | Biliary Tract Neoplasms |
| D004067 | Digestive System Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D001660 | Biliary Tract Diseases |
| D004066 | Digestive System Diseases |
| D005705 | Gallbladder Diseases |
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| ID | Term |
|---|---|
| C520255 | 130-nm albumin-bound paclitaxel |
| C000632826 | sintilimab |
| D000068258 | Bevacizumab |
| ID | Term |
|---|---|
| D061067 | Antibodies, Monoclonal, Humanized |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
| D007162 | Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
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