Combination of Gemcitabine, Albumin-paclitaxel , Sintilimab and Bevacizumab in Unresectable Gallbladder Cancer

NCT05757336 | Recruiting Phase 2

• 1 other identifier: GWK-2022-08
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Gallbladder Cancer; Initially Unresectable; the First Line Treatment

Outcome Measures

Primary Outcomes (2)

• 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

Secondary Outcomes (4)

• disease control rate

  3 weeks

• progress-free survival

  3 weeks

• overall survival

  3 weeks

• Proportion of acceptable radical resection of primary lesions

  3 weeks

Study Arms (1)

combined treatment group

EXPERIMENTAL

Combination of Gemcitabine, Nab-paclitaxel, Sintilimab and Bevacizumab GC regimen: up to the results of safety run-in stage * Dose A: gemcitabine 1000mg/m2, paclitaxel for injection (albumin-bound) 125mg/m2 iv Q3W * Dose B: gemcitabine 800mg/m2, paclitaxel for injection (albumin-bound) 100mg/m2 iv Q3W Sintilimab: 200mg, iv, d1, q3w Bevacizumab: 7.5mg/kg, d1, q3w

Drug: Combination of Gemcitabine, Nab-paclitaxel, Sintilimab and Bevacizumab

Interventions

Combination of Gemcitabine, Nab-paclitaxel, Sintilimab and Bevacizumab DRUG

Combination of Gemcitabine, Nab-paclitaxel, Sintilimab and Bevacizumab

combined treatment group

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \. 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:
• Absolute value of neutrophils (ANC) ≥ 1.5x109/L and platelets ≥ 90×109/L without using granulocyte colony-stimulating factor in the past 14 days;
• Hemoglobin \> 9g/dL without blood transfusion or use of erythropoietin in the past 21 days;
• Total bilirubin ≤ 3 × upper limit of normal (ULN);
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) are ≤2.5×ULN (patients with liver metastases are allowed ALT or AST ≤5×ULN);
• Alkaline phosphatase (AKP) ≤2.5×ULN
• Creatinine clearance rate (calculated using the Cockcroft-Gault formula) ≥ 50 ml/min;
• Good coagulation function, defined as international normalized ratio (INR) or prothrombin time (PT) ≤ 1.5 times ULN;
• 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.
• 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

You may not qualify if:

• 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);
• Currently participating in interventional clinical research treatment, or receiving other research drugs or using research devices within 4 weeks before the first administration;
• 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;
• 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;
• Imaging shows tumor invasion/infiltration of large blood vessels or bleeding tendency assessed by researchers or radiologists;
• Received major surgical treatment within 4 weeks before the first study drug administration (except for surgery for biopsy);
• Severe unhealed wound ulcers or fractures;
• 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;
• 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);
• Have hereditary bleeding tendency or coagulation disorder, or history of thrombosis;
• 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)
• 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)
• Known allogeneic organ transplantation (except corneal transplantation) or allogeneic hematopoietic stem cell transplantation
• 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)
• 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

Sponsors & Collaborators

• Lu Wang, MD, PhD: lead

Study Sites (1)

Fudan University Shanghai Cancer Center

Shanghai, 200032, China

RECRUITING

MeSH Terms

Conditions

Gallbladder Neoplasms

Interventions

130-nm albumin-bound paclitaxel; sintilimab; Bevacizumab

Condition Hierarchy (Ancestors)

Biliary Tract Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Biliary Tract Diseases; Digestive System Diseases; Gallbladder Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Central Study Contacts

Lu Wang

CONTACT

+86-18121299357; w.lr@hotmail.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Head of liver surgery department

Study Record Dates

• First Submitted: February 24, 2023
• First Posted: March 7, 2023
• Study Start: December 22, 2022
• Primary Completion: December 22, 2024
• Study Completion (Estimated): December 22, 2026
• Last Updated: March 7, 2023

Record last verified: 2023-02

Locations

CN (1)