Nab-Paclitaxel and Gemcitabine Plus Camrelizumab and Radiotherapy for Locally Advanced Pancreatic Adenocarcinoma

Study Overview
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Brief Summary
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The study is a prospective and observational cohort study. The purpose is to to investigate the safety and efficacy of nab-paclitaxel and gemcitabine plus camrelizumab and radiotherapy versus nab-paclitaxel and gemcitabine alone for locally advanced pancreatic adenocarcinoma (PDAC)

Detailed Description
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We will prospectively collect 100 patients who receive nab-paclitaxel and gemcitabine plus camrelizumab and radiotherapy or nab-paclitaxel and gemcitabine alone. Data will be stored in a private database. The process of data collection will be supervised and regular data examination will be performed.

Official Title
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Nab-Paclitaxel and Gemcitabine Plus Camrelizumab and Radiotherapy Versus Nab-Paclitaxel and Gemcitabine Alone for Locally Advanced Pancreatic Adenocarcinoma

Conditions
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PDAC - Pancreatic Ductal Adenocarcinoma

Intervention / Treatment
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* Radiation: Radiotherapy
* Drug: Nab-paclitaxel
* Drug: Gemcitabine
* Drug: Camrelizumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: aged 18-75 years; histologically or cytologically proven diagnosis of pancreatic adenocarcinoma; treatment-naive locally advanced pancreatic cancer (locally advanced status was determined by our multidisciplinary team based on the National Comprehensive Cancer Network definitions); no distant metastasis as defined by CT or MRI of the chest, abdomen and pelvis; at least 1 measurable lesion based on the Response Evaluation Criteria in Solid Tumors criteria (RECIST) 1.1; an Eastern Cooperative Oncology Group (ECOG) performance status score of 0 to 1; adequate hematological, liver, renal function: absolute neutrophil count≥1500 cell/mm3; platelet count≥100×109/L; hemoglobin concentration >90 g/L; albumin≥30 g/L ; total bilirubin<1.5 times the upper limit of normal; alanine aminotransferase and aspartate aminotransferase≤3 times the upper limit of normal; serum creatinine concentration<1.5 times the upper limit of the normal range or less and creatinine clearance rate≥45 mL/min; life expectancy of at least 3 months. Exclusion Criteria: with any other malignancy within the 5 years before enrolment; with active infections (bacterial, viral, or fungal) requiring systematic treatment, with hepatitis B or C infection, or a history of HIV infection, or receiving immunosuppressive therapy; with peripheral sensory neuropathy at a grade >1; with a history of allergy or hypersensitivity to the study drugs; pregnant or breast feeding women, reproductive aged women who refused to take adequate contraceptive measures during the study.

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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Nab-Paclitaxel+Gemcitabine+Camrelizumab+Radiotherapy<br>Chemotherapy consisted of eight 21-day cycles of nab-paclitaxel plus gemcitabine (nab-paclitaxel 125 mg/m² by intravenous infusion for approximately 30-45 mins, followed by gemcitabine 1000mg/m² intravenous infusion for approximately 30 mins on days 1 and 8). Anti-PD-1 antibody (camrelizumab, Hengrui Medicine Co., Ltd) 200 mg was administered intravenously for 30 mins every three weeks. During the chemotherapy-treated period, camrelizumab was administered on day 1 of each 21-day cycle before the infusion of chemotherapy. Radiotherapy started after two cycles of chemotherapy. A total radiation dose greater than 50 Gy without damaging organ function was the essential requirement. | Radiation: Radiotherapy<br>* Radiotherapy started after two cycles of chemotherapy. External beam radiation therapy was performed using an intensity modulated radiation therapy technique. The gross target volume included the gross primary tumor and positive regional lymph nodes as defined by the multiphasic imaging. A total radiation dose greater than 50 Gy without damaging organ function was the essential requirement.<br>Drug: Nab-paclitaxel<br>* Eight 21-day cycles of nab-paclitaxel 125 mg/m² by intravenous infusion for approximately 30-45 mins on days 1 and 8.<br>Drug: Gemcitabine<br>* Eight 21-day cycles of gemcitabine 1000mg/m² intravenous infusion for approximately 30 mins on days 1 and 8.<br>Drug: Camrelizumab<br>* Anti-PD-1 antibody (camrelizumab, Hengrui Medicine Co., Ltd) 200 mg was administered intravenously for 30 mins every three weeks. During the chemotherapy-treated period, camrelizumab was administered on day 1 of each 21-day cycle before the infusion of chemotherapy.<br>|
| Nab-Paclitaxel+Gemcitabine<br>Chemotherapy consisted of eight 21-day cycles of nab-paclitaxel plus gemcitabine (nab-paclitaxel 125 mg/m² by intravenous infusion for approximately 30-45 mins, followed by gemcitabine 1000mg/m² intravenous infusion for approximately 30 mins on days 1 and 8). | Drug: Nab-paclitaxel<br>* Eight 21-day cycles of nab-paclitaxel 125 mg/m² by intravenous infusion for approximately 30-45 mins on days 1 and 8.<br>Drug: Gemcitabine<br>* Eight 21-day cycles of gemcitabine 1000mg/m² intravenous infusion for approximately 30 mins on days 1 and 8.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival | defined as the time from randomization until disease progression or death from any cause, whichever happens first. Patients who withdraw or who are lost to follow-up will be censored at the date last known to be alive and progression free. Patients not having an event will be censored at the date last seen alive. | two years | 
| Overall survival | defined as the time from randomization until death from any cause. Patients who withdraw or who are lost to follow-up will be censored at the date last known to be alive. Patients remaining alive throughout the duration of the study will have their survival time censored on the date last seen alive. | two years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse events | adverse events during the treatment period using Common Terminology Criteria for Adverse Events (CTCAE) (version 5.0). | two years | 
| Tumor response | measured according to the Response Evaluation Criteria in Solid Tumors (RECIST) criteria 1.1 by means of computed tomography (CT) or magnetic resonance imaging (MRI) at each follow-up. | two years |