Metronomic Chemotherapy With Capecitabine for Pancreatic Cancer

Study Overview
=================
Brief Summary
-----------------
The latest guidelines recommend Gemcitabine plus Capecitabine as the first choice of adjuvant chemotherapy for pancreatic cancer patients in good physical condition. In order to prolong the survival of patients and improve the cure rate, metronomic chemotherapy with capecitabine is a safe, effective and economical treatment mode after adjuvant chemotherapy. This study is trying to determine that compared with observation group, if capecitabine metronomic medication is a better choice after adjuvant chemotherapy.

Detailed Description
-----------------
Capecitabine (Xeloda ®) is currently the most biologically active oral fluoropyrimidine drug, and is widely used in adjuvant therapy for pancreatic cancer. It is usually taken twice a day (in the morning and in the evening) for 2 weeks, followed by a 1 week break before repeating the next dosage cycle. In this study, capecitabine will be prescribed as dosage of 500mg/m2, and maintain for a whole year after the standard treatment in stage II/III pancreatic cancer patients. 1 year disease-free survival is set as the primary outcome, OS, RFS, AEs and exploratory biomarkers including effects of metronome chemotherapy on immune cells, such as NK cells, T cells, TAMs, B cells, etc are also observed as the secondary outcomes. Statistical analysis are made to see compared with observation group, whether this metronomic therapy of capecitabine ( 500mg/m2) will bring benefit to pancreatic cancer patients.

Official Title
-----------------
A Multi-center, II Phase，Randomized Controlled Clinical Study of Capecitabine Metronomic Chemotherapy After Gemcitabine Plus Capecitabine Standard Adjuvant Therapy for Stage II/III Pancreatic Cancer

Conditions
-----------------
Pancreatic Cancer

Intervention / Treatment
-----------------
* Drug: Capecitabine


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Histologically confirmed pancreatic invasive ductal adenocarcinoma. The patient underwent surgery for pancreatic tumor resection, and no gross residual lesions were found postoperatively (R2). Stage II/III pancreatic cancer was determined according to AJCC/UICC TNM stage eighth. At least 6 cycles of gemcitabine plus capecitabine chemotherapy have been completed. Age 18-70 years old, gender not limited. ECOG performance score is 0 or 1. Without dysphagia, able to tolerate oral administration. No relevant clinical or imaging evidence of recurrence or metastasis showing within the 28 days before random. Chemotherapy with capecitabine combined with gemcitabine regimen was given within 12 weeks after surgery, and last chemotherapy to random time ≤ 6 weeks. Adequate bone marrow, liver, and kidney function in measurements taken within 7 days before registration ： Hemoglobin ≥ 90 g/L, Platelet count ≥ 100×109/L, Absolute granulocyte count ≥ 1.5×109/L. i. Note: patients should not receive blood transfusion or growth factor support within 14 days before collection of blood samples. Serum creatinine≤ 1.5 ULN, and calculated creatinine clearance of ≥ 60 mL/min/1.73m2. AST and ALT ≤ 2.5 X ULN, serum total bilirubin ≤ 1.5 X ULN (Patients with Gilbert syndrome with total bilirubin≤ 3 X ULN can be enrolled). INR or PT ≤ 1.5×ULN，unless the patient is receiving anticoagulant therapy and the PT value is within the expected therapeutic range of the anticoagulant. Electrocardiogram and cardiac function were not contraindicated in chemotherapy. Women should have a negative pregnancy test, and all the patients have no planning within 3 years and should take contraceptive measures during treatment. Informed consent form signed. Exclusion Criteria: Other pathological types of pancreatic malignancies (e.g. neuroendocrine carcinoma, large cell carcinoma, signet ring cell carcinoma, etc.). With distant metastasis or malignant pleural effusion. Pregnant and breast-feeding women. Unable to oral medication. Previous or concurrent malignancies, excluding curatively treated in situ carcinoma of the cervix or non-melanoma skin cancer, unless at least 5 years have elapsed since last treatment and the patient is considered cured. A history of transient ischemic attack, cerebrovascular accident, thrombosis, or thromboembolism (pulmonary embolism or deep venous thrombosis) within 180 days before randomization. Any of the following uncontrolled or severe cardiovascular disease history: Myocardial infarction occurred 180 days before randomization. Uncontrolled angina occurred within 180 days before randomization. Heart failure of class III or IV (according to New York Heart Association functional classification). Uncontrolled hypertension after appropriate treatment (e.g. Systolic blood pressure ≥150mmHg or diastolic blood pressure ≥90mmHg for 24h or longer). Arrhythmias that require treatment, including pacemakers. Serious drug allergy. Uncontrolled diabetes or systemic infection. Known dihydro pyrimidine dehydrogenase (DPD) deficiency. Any other reasons the investigator considers the patient should not participate in the study. Without personal freedom and independent civil capacity. Already enrolled into other clinical trials.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Capecitabine metronomic chemotherapy<br>Capecitabine 500mg/m2 po qd | Drug: Capecitabine<br>* Oral fluorouracil<br>* Other names: Xeloda;|
| No Intervention: Observation<br>Observation | |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| One year disease-free survival | was defined as the rate of disease recurrence, metastasis or death due to disease progression within 1 year after the surgery | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) | was defined as the time from the date of surgery until the date of any death occurred | 5 year | 
| Recurrence-free Survival (RFS) | was defined as the time from the date of surgery until the date of local recurrence of the tumor | 1 year | 
| AEs | Hand and foot syndrome and other treatment related AE | 5 year | 
| Exploratory biomarkers | including effects of metronome chemotherapy on immune cells, such as NK cells, T cells, TAMs, B cells, etc | 1 yaer |