Phase 2 Trial of Gemcitabine vs S-1 vs Gemcitabine Plus Nab-paclitaxel as Adjuvant Chemotherapy of Post-operative Pancreatic Cancer Patients

Study Overview
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Brief Summary
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Pancreatic cancer is one of the deadliest tumor types, there is no effective treatment method clinically. Recently radical surgical resection is recommended for this cancer, How to improve the survival rate of patients is the doctors' goals . Postoperative chemotherapy can partly raise post-operative survival rate. the purpose of this study is to three chemotherapy regimens(gemcitabine monotherapy, S-1 monotherapy and combining nab-paclitaxel with gemcitabine),which is best regimens for raising patients' survival rate, and will provide a chemotherapy choice for clinic therapy of pancreatic cancer.

Official Title
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Phase 2 Trial of Gemcitabine vs S-1 vs Gemcitabine Plus Nab-paclitaxel as Adjuvant Chemotherapy of Post-operative Pancreatic Cancer Patients

Conditions
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Cancer of Pancreas

Intervention / Treatment
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* Drug: Nab-paclitaxel plus Gemcitabine
* Drug: Gemcitabine monotherapy
* Drug: S-1 monotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed informed-consent form. Man or woman aged 18 years to 80 years. Histologically confirmed pancreatic carcinoma, and the histological type is ductal adenocarcinoma. Mild (Child-Pugh A), moderate (Child-Pugh B) and some preferable severe (Child-Pugh C, <=10) hepatic dysfunction according to the Child-Pugh Scoring system criteria. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-3, with life expectation of no less than 12 weeks. Adequate bone marrow function as evidenced by absolute neutrophil count (ANC) ≥1.5 x 109/L; platelets ≥ 70 x 109/L; hemoglobin ≥ 8.0 g/dL. Albumin ≥ 30 g/L. Adequate hepatic function as evidenced by Alanine aminotransferase (ALT) and Aspartate aminotransferase (AST) ≤ 5 x upper limit of normal (ULN); Serum total bilirubin ≤ 1.5 x ULN; Serum creatinine ≤ 1.5 x ULN. Females of childbearing potential must have a negative serum pregnancy test and must not breast-feed before the first dose. Male also need contraception. Willing and able to comply with study procedures for the duration of the study. Exclusion Criteria: Hypertension, and unable to drop to normal level (systolic pressure >140 mmHg, diastolic pressure >90 mmHg) after treatment. Patients have active cardiac disease including any of the following: In resting state, average correction QTc > 470 msec on mean value of 3 times screening ECGs. Any clinically significant abnormal ECG form, for example, complete left bundle branch block, 3-degree atrioventricular block, 2-degree atrioventricular block, or PR interval > 250 msec. Any factors may increase the risk of QTc prolongation or arrhythmic event. Left ventricular ejection fraction (LVEF) < 50%. Patient weight still in losing period. History of gastrointestinal bleeding or a gastrointestinal bleeding tendency, such as esophageal varices with high risk of bleeding, local active ulcerative lesions, fecal occult blood test>= (+ +) within the past 6 months, shall not enter the trial. If fecal occult blood test (+), the patient is requested for gastroscopy. Patients with abdominal fistula, gastrointestinal perforation or abdominal abscess within the past 28 days, should not enter the trial. Patients with coagulant function abnormality (INR > 1.5 or prothrombin time (PT) > ULN + 4 sec), with bleeding tendency or are treated with thrombolytic or anticoagulant therapy. Patients with unstable or serious concurrent medical conditions are excluded. The researcher evaluates that the patient who is not suitable for participation in the study. Patients with active infection, for example, HBV, HCV, or HIV. Uncontrollable nausea, vomit, chronic gastrointestinal disorders leading to unable to swallow drugs, which may affect the fully absorption of S-1. Patients with mental illness, or with psychiatric history of drug abuse.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Nab-paclitaxel plus Gemcitabine<br>Nanoparticle albumin-bound paclitaxel is given at 100mg/m2 intravenously over 30 minutes in combination with Gemcitabine 1000mg/m2 intravenously on day 1 and 8 of each 21-days cycle. Number of cycle: 6 cycles. | Drug: Nab-paclitaxel plus Gemcitabine<br>* Nanoparticle albumin-bound paclitaxel is given at 100mg/m2 intravenously over 30 minutes in combination with Gemcitabine 1000mg/m2 intravenously on day 1 and 8 of each 21-days cycle. Number of cycle: 6 cycles.<br>* Other names: GEMXAR;|
| Experimental: Gemcitabine monotherapy<br>Gemcitabine is given at 1000mg/m2 intravenously on day 1 and 8 of each 21-days cycle. Number of cycle: 6 cycles. | Drug: Gemcitabine monotherapy<br>* Gemcitabine is given at 1000mg/m2 intravenously on day 1 and 8 of each 21-days cycle. Number of cycle: 6 cycles.<br>* Other names: GEMXAR;|
| Experimental: S-1 monotherapy<br>S-1 is orally administered (40-60 mg according to the body surface, Bid) on day 1-14 of each 21-days cycle. Number of cycle: 6 cycles. | Drug: S-1 monotherapy<br>* S-1 is orally administered (40-60 mg according to the body surface, Bid) on day 1-14 of each 21-days cycle. Number of cycle: 6 cycles.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease free survival(DFS) | To determine the DFS of post-operative patients with pancreatic cancer | 3 years | 
| overall survival time (OS) | To determine the OS post-operative patients with pancreatic cancer | 5 years | 
| median overall survival time (mOS) | To determine the mOS post-operative patients with pancreatic cancer | 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate(ORR) | All patients must be considered in response analysis, including those who discontinue treatment or who die for any reason prior to response evaluations | 3 years | 
| Quality of Life Assessment |  | 3 years | 
| safety profile | Treatment-emergent adverse events, drug-related adverse events will be analysed by 3 groups | 3 years | 
| Disease control rate(DCR) |  | 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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S-1, nab-paclitaxel