Phase II, Single-arm, Exploratory Study to Evaluate the Safety and Effectiveness of Durvalumab Combined With Chemotherapy Neoadjuvant Therapy of Biliary Tract Cancer
Overview
- Phase
- Phase 2
- Intervention
- Cisplatin
- Conditions
- Resectable Biliary Tract Cancer
- Sponsor
- Tianjin Medical University Cancer Institute and Hospital
- Enrollment
- 40
- Locations
- 1
- Primary Endpoint
- Rate of completion of all preoperative and operative therapy
- Status
- Recruiting
- Last Updated
- 3 years ago
Overview
Brief Summary
This phase II trial studies how well gemcitabine, cisplatin, nab-paclitaxel and durvalumab work before surgery in treating participants with Biliary Tract Cancer. The international multicenter phase III clinical study TOPAZ-1 has confirmed that durvalumab combined with gemcitabine and cisplatin can bring survival benefits to advanced BTC. Drugs used in chemotherapy, such as nab-paclitaxel, cisplatin, and gemcitabine, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving combination chemotherapy and Durvalumab before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Confirmed as malignant tumor of biliary tract by pathological diagnosis;
- •Computed tomography (CT) or magnetic resonance imaging (MRI) shall be performed with high-quality cross-sectional imaging, and diagnosed as resectable high-risk biliary malignant tumors, limited to the liver, bile duct and/or regional lymph nodes (at least one of the following criteria must be met) :
- •T-stage ≥ Ib (Ib-IV)
- •Solitary lesion \> 5 cm
- •Multifocal tumors or satellite lesions present confined to the same lobe of the liver as the dominant lesion but still technically resectable
- •Presence of major vascular invasion but still technically resectable
- •Suspicious or involved regional lymph nodes (N1)
- •No distant extrahepatic disease (M0)
- •The patient's gender is not limited, and the age is 18-75 years old; Life expectancy\>3 months;
- •Within one week of enrollment, the ECOG PS score was 0 or 1;
Exclusion Criteria
- •Patients who received PD-1, PD-L1, PD-L2, CTLA-4 inhibitors before enrollment, or patients who directly received another stimulatory or co inhibitory T cell receptor (such as CTLA-4, CD137);
- •Used any other research drugs within 4 weeks before enrollment;
- •Any active autoimmune disease or history of autoimmune disease (such as interstitial pneumonia, uveitis, enteritis, hepatitis, hypophysitis, vasculitis, myocarditis, nephritis, hyperthyroidism, hypothyroidism after hormone replacement therapy); Patients with childhood asthma who have completely alleviated and do not need any intervention or leukorrhea after adulthood can be included, but patients who need medical intervention with bronchodilators cannot be included;
- •With congenital or acquired immune deficiency, such as people infected with human immunodeficiency virus (HIV), active hepatitis B (HBV DNA 500IU/ml), hepatitis C (hepatitis C antibody is positive, and HCV-RNA is higher than the detection limit of the analytical method) or people with hepatitis B and hepatitis C co infection;
- •Severe infection (such as intravenous drip of antibiotics, antifungal or antiviral drugs) occurred within 4 weeks before the first drug administration, or fever of unknown cause\>38.5 ° C occurred during screening/before the first drug administration;
- •History of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation;
- •Test drug allergy;
- •Suffering from uncontrollable mental illness;
- •Peripheral neuropathy of grade 2 or above according to CTCAE 4.
- •In CTCAE 4.0, grade 2 sensory neuropathy is defined as "moderate symptoms; restriction of activities of daily living (ADL)";
Arms & Interventions
Gemcitabine, cisplatin, nab-paclitaxel, durvalumab
Participants receive nab-paclitaxel over 30 minutes, cisplatin over 60 minutes, and gemcitabine over 30 minutes on days 1 and 8; durvalumab over 60 minutes on days 1. Treatment repeats every 21 days for up to 3 courses in the absence of disease progression or unacceptable toxicity. Participants with stable disease (SD), partial response (PR), or complete response (CR) then undergo standard of care hepatectomy with portal lymphadenectomy.
Intervention: Cisplatin
Gemcitabine, cisplatin, nab-paclitaxel, durvalumab
Participants receive nab-paclitaxel over 30 minutes, cisplatin over 60 minutes, and gemcitabine over 30 minutes on days 1 and 8; durvalumab over 60 minutes on days 1. Treatment repeats every 21 days for up to 3 courses in the absence of disease progression or unacceptable toxicity. Participants with stable disease (SD), partial response (PR), or complete response (CR) then undergo standard of care hepatectomy with portal lymphadenectomy.
Intervention: Gemcitabine
Gemcitabine, cisplatin, nab-paclitaxel, durvalumab
Participants receive nab-paclitaxel over 30 minutes, cisplatin over 60 minutes, and gemcitabine over 30 minutes on days 1 and 8; durvalumab over 60 minutes on days 1. Treatment repeats every 21 days for up to 3 courses in the absence of disease progression or unacceptable toxicity. Participants with stable disease (SD), partial response (PR), or complete response (CR) then undergo standard of care hepatectomy with portal lymphadenectomy.
Intervention: Nab-paclitaxel
Gemcitabine, cisplatin, nab-paclitaxel, durvalumab
Participants receive nab-paclitaxel over 30 minutes, cisplatin over 60 minutes, and gemcitabine over 30 minutes on days 1 and 8; durvalumab over 60 minutes on days 1. Treatment repeats every 21 days for up to 3 courses in the absence of disease progression or unacceptable toxicity. Participants with stable disease (SD), partial response (PR), or complete response (CR) then undergo standard of care hepatectomy with portal lymphadenectomy.
Intervention: Durvalumab
Outcomes
Primary Outcomes
Rate of completion of all preoperative and operative therapy
Time Frame: Up to 9 weeks after study start
Completion of all therapy rate will be recorded.
Incidence of adverse events
Time Frame: Up to 1 years after study start
Will be monitored using method of Thall, Simon and Estey, and will be tabulated by the maximum reported Common Terminology Criteria for Adverse Events (CTCAE) grade.
Secondary Outcomes
- Recurrence-free survival (RFS)(Up to 1 years after study start)
- Overall survival (OS)(Up to 1 years after study start)
- Response rate defined as the percentage of patients who will have complete response (CR), partial response (PR) or stable disease (SD) after the neoadjuvant therapy(Up to 9 weeks after study start)
- Rate of R0 resection(Up to 9 weeks after study start)