Trial Title:
Combination of Gemcitabine, Albumin-paclitaxel , Sintilimab and Bevacizumab in Unresectable Gallbladder Cancer
NCT ID:
NCT05757336
Condition:
Gallbladder Cancer
Initially Unresectable
the First Line Treatment
Conditions: Official terms:
Gallbladder Neoplasms
Paclitaxel
Bevacizumab
Gemcitabine
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Combination of Gemcitabine, Nab-paclitaxel, Sintilimab and Bevacizumab
Description:
Combination of Gemcitabine, Nab-paclitaxel, Sintilimab and Bevacizumab
Arm group label:
combined treatment group
Summary:
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.
Criteria for eligibility:
Criteria:
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:
1. Absolute value of neutrophils (ANC) ≥ 1.5x109/L and platelets ≥ 90×109/L without
using granulocyte colony-stimulating factor in the past 14 days;
2. Hemoglobin > 9g/dL without blood transfusion or use of erythropoietin in the past 21
days;
3. Total bilirubin ≤ 3 × upper limit of normal (ULN);
4. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) are ≤2.5×ULN
(patients with liver metastases are allowed ALT or AST ≤5×ULN);
5. Alkaline phosphatase (AKP) ≤2.5×ULN
6. Creatinine clearance rate (calculated using the Cockcroft-Gault formula) ≥ 50
ml/min;
7. Good coagulation function, defined as international normalized ratio (INR) or
prothrombin time (PT) ≤ 1.5 times ULN;
8. Normal thyroid function, defined as thyroid-stimulating hormone (TSH ≤ 10) within
the normal range; thyroid dysfunction without clinical significance after thyroid
hormone supplementation can also be included.
9. Myocardial enzyme spectrum is within the normal range (such as simple laboratory
abnormalities that are judged by the investigator to have no clinical significance
are also allowed to enter the group); 9. For female subjects of childbearing age,
they should receive a urine or serum pregnancy test within 3 days before receiving
the first study drug administration (day 1 of cycle 1) and the result is negative.
If the urine pregnancy test result cannot be confirmed negative, a blood pregnancy
test will be ordered. Women of non-reproductive age are defined as postmenopausal
for at least 1 year, or who have undergone surgical sterilization or hysterectomy
10. If there is a risk of pregnancy, all subjects (regardless of male or female)
need to use contraceptive measures with an annual failure rate of less than 1%
during the entire treatment period until 120 days after the last study drug
administration
Exclusion Criteria:
1. Other malignant diseases outside the biliary tract diagnosed within 5 years before
the first administration (excluding radically cured skin basal cell carcinoma, skin
squamous cell carcinoma, and/or radically resected carcinoma in situ, radically
cured thyroid papillary carcinoma can also be included after surgery);
2. Currently participating in interventional clinical research treatment, or receiving
other research drugs or using research devices within 4 weeks before the first
administration;
3. Active autoimmune disease requiring systemic treatment (such as the use of
disease-modifying drugs, glucocorticoids or immunosuppressants) occurred before the
first dose. Replacement therapies (eg, thyroxine, insulin, or physiologic
glucocorticoids for adrenal or pituitary insufficiency) are not considered systemic
therapy. Known history of primary immunodeficiency. Only patients with autoimmune
antibody positive need to confirm whether there is an autoimmune disease according
to the investigator's judgment;
4. Active hemoptysis (spitting up at least 2.5ml or 1/2 teaspoon of fresh blood) within
3 months before the first study drug administration, and active gastrointestinal
bleeding within 3 months before administration;
5. Imaging shows tumor invasion/infiltration of large blood vessels or bleeding
tendency assessed by researchers or radiologists;
6. Received major surgical treatment within 4 weeks before the first study drug
administration (except for surgery for biopsy);
7. Severe unhealed wound ulcers or fractures;
8. Current or recent (within 10 days before receiving the first dose of the study drug)
use of aspirin (>325mg/day) or other non-steroidal anti-inflammatory drugs known to
inhibit platelet function for 10 consecutive days;
9. Current or recent (within 10 days before receiving the first dose of study drug)
treatment with full-dose oral or parenteral anticoagulant or thrombolytic agent for
10 consecutive days Note: The prophylactic use of small doses of anticoagulants is
allowed: on the premise that the international normalized ratio (INR) of prothrombin
time is ≤1.5, small doses of warfarin (≤1 mg/d) and low doses of heparin are allowed
for prophylactic purposes (≤12,000 U/d) or low-dose aspirin (≤100mg/d);
10. Have hereditary bleeding tendency or coagulation disorder, or history of thrombosis;
11. Are receiving systemic glucocorticoid therapy (excluding nasal spray, inhalation or
other routes of topical glucocorticoid) or any other form of immunosuppressive
therapy within 4 weeks before the first dose of the study Note: Physiological doses
of glucocorticoids are permitted (≤10 mg/day of prednisone or equivalent)
12. There is clinically uncontrollable pleural effusion/abdominal effusion (patients who
do not need drainage or stop drainage for 3 days without significant increase in
effusion can be enrolled)
13. Known allogeneic organ transplantation (except corneal transplantation) or
allogeneic hematopoietic stem cell transplantation
14. Those who are known to be allergic to active ingredients or excipients of the study
drug sintilimab, bevacizumab, gemcitabine hydrochloride for injection, paclitaxel
for injection (albumin-bound type)
15. Has not recovered adequately from any intervention-induced toxicity and/or
complications (ie, ≤ Grade 1 or reached baseline, excluding fatigue or alopecia)
prior to initiating treatment
16. Known history of human immunodeficiency virus (HIV) infection (ie HIV 1/2 antibody
positive)
17. Untreated active hepatitis B (defined as HBsAg positive and detection of HBV-DNA
copy number greater than the upper limit of normal value of the laboratory
laboratory of the research center)
Note: Hepatitis B subjects who meet the following criteria can also be enrolled:
1. If the HBV viral load before the first administration is <2.5×103 copies/ml (500
IU/ml), the subject should receive anti-HBV treatment during the entire study
treatment period
2. For subjects whose anti-HBc (+), HBsAg (-), anti-HBs (-) and HBV viral load are less
than the upper limit of normal value in the laboratory department of the research
center, they do not need to receive preventive anti-HBV treatment, but they need to
be closely monitored. Monitoring for viral reactivation 18. Subjects with active HCV
infection (HCV antibody positive and HCV-RNA level higher than the lower limit of
detection) 19. Except for those who have received live attenuated vaccines within 4
weeks before the first dose of the new crown vaccine 20. Pregnant or lactating women
21. Esophageal or gastric variceal bleeding events caused by portal hypertension in
the past 6 months; known severe (G3) varices in endoscopy within 3 months before the
first administration; evidence of portal hypertension (including Imaging examination
revealed that the length of splenomegaly exceeds 10 cm and the platelets are less
than 100×109/L), and the researchers evaluated the risk of bleeding as high 22. Any
life-threatening bleeding events occurred in the past 3 months, including the need
for blood transfusion therapy, surgery or local therapy, continuous drug therapy 23.
Arterial and venous thromboembolic events within the past 6 months, including
myocardial infarction, unstable angina, cerebrovascular accident or transient
ischemic attack, pulmonary embolism, deep vein thrombosis or any other serious
history of thromboembolism. Implantable venous port or catheter-derived thrombosis,
or superficial venous thrombosis, unless the thrombus is stabilized after
conventional anticoagulant therapy 24. History of gastrointestinal perforation
and/or fistula, intestinal obstruction (including incomplete intestinal obstruction
requiring parenteral nutrition), extensive bowel resection (partial colon resection
or extensive small bowel resection, complicated by chronic diarrhea) within the past
6 months , Crohn's disease, ulcerative colitis, or long-term chronic diarrhea; 25.
Presence of any serious or uncontrolled systemic disease, such as:
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
Gender:
All
Minimum age:
18 Years
Maximum age:
75 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Fudan University Shanghai Cancer Center
Address:
City:
Shanghai
Zip:
200032
Country:
China
Status:
Recruiting
Contact:
Last name:
Lu Wang
Phone:
+8618121299357
Email:
w.lr@hotmail.com
Start date:
December 22, 2022
Completion date:
December 22, 2026
Lead sponsor:
Agency:
Lu Wang, MD, PhD
Agency class:
Other
Source:
Fudan University
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05757336
