Borderline Resectable Pancreatic Cancer Neoadjuvant Chemoradiotherapy Clinicaltrial-1

Study Overview
=================
Brief Summary
-----------------
This study is to investigate whether neoadjuvant chemotherapy plus SBRT results in better outcomes compared with neoadjuvant chemotherapy alone and also compare the efficacy of gemcitabine plus nab-paclitaxel with SBRT and S-1 plus nab-paclitaxel with SBRT.

Detailed Description
-----------------
This research study is a Phase II clinical trial that investigate whether neoadjuvant chemotherapy plus SBRT results in better outcomes compared with neoadjuvant chemotherapy alone and also compare the efficacy of gemcitabine plus nab-paclitaxel with SBRT and S-1 plus nab-paclitaxel with SBRT. It is known that neoadjuvant therapy is vital for improved survival, which has been confirmed in previous studies that neoadjuvant chemotherapy with or without radiotherapy provides superior overall compared with upfront surgery. However, question of whether the addition of radiotherapy to neoadjuvant chemotherapy can improve prognosis compared with chemotherapy alone is a challenging matter. Also, no studies have evaluated the efficacy of S-1 as the neoadjuvant chemotherapy regimen for BRPC albeit similar prognosis has been found between S-1 and gemcitabine in advanced pancreatic cancer. In this trial, patients with biopsy and radiographically confirmed BRPC will be randomly allocated into three groups: neoadjuvant gemcitabine plus nab-paclitaxel, neoadjuvant gemcitabine plus nab-paclitaxel with SBRT and neoadjuvant S-1 plus nab-paclitaxel with SBRT. Surgical resection will be performed 3 weeks after SBRT. The primary endpoint is overall survival. The secondary outcomes are progression free survival, pathological complete response rate, R0 resection rate and incidence of adverse effects. If results show the survival benefits of neoadjuvant chemotherapy plus SBRT and similar outcomes between S-1 and gemcitabine, it may provide evidence of clinical practice of this modality for BRPC.

Official Title
-----------------
Comparisons of Different Neoadjuvant Chemotherapy Regimens With or Without Stereotactic Body Radiation Therapy for Borderline Resectable Pancreatic Cancer: Study Protocol of a Prospective, Randomized Phase II Trial

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

Intervention / Treatment
-----------------
* Drug: Neoadjuvant gemcitabine plus nab-paclitaxel
* Drug: Neoadjuvant gemcitabine plus nab-paclitaxel with SBRT
* Drug: Neoadjuvant S-1 plus nab-paclitaxel with SBRT


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age≥18 years old and ≤80 years old; Histological proven pancreatic adenocarcinoma; Borderline resectable pancreatic cancer proven by imaging examinations via multidisciplinary approaches according to NCCN guidelines; No prior chemotherapy or radiotherapy; ECOG of 0 or 1; Routine blood test: absolute neutrophil count>1500/mm3, platelet>100000/mm3; Normal liver function: serum total bilirubin≤2.0mg/dl, ALT and AST<2.5 times of the upper limit of normal value; Normal kidney function: serum creatinine<1.5 times of the upper limit of normal value or creatinine clearance rate>45ml/min; No severe comorbidities. Exclusion Criteria: Metastatic pancreatic cancer; Patients who had surgeries, chemotherapy or other treatments before inclusion; Impaired organ functions: heart failure (New York Heart Association III-IV), coronary heart disease, myocardial infarction within 6 months, severe cardiac arrhythmia and respiratory failure; Confirmed other cancer within 5 years; Pregnant women or lactating women; Patients enrolled in other clinical trials or incompliant of regular follow up; Patients who did not provide an informed consent.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 80 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Group A of neoadjuvant chemotherapy<br>Neoadjuvant gemcitabine plus nab-paclitaxel is used in this group. Intravenous administration of gemcitabine (1000mg/m2) and nab-paclitaxel (125 mg/m2) are initiated on day 1, 8 and 15 during each 4-week cycle, which will repeat for 3 cycles. And surgical resection is performed after completion of the whole chemotherapy. | Drug: Neoadjuvant gemcitabine plus nab-paclitaxel<br>* Neoadjuvant gemcitabine plus nab-paclitaxel is used in the intervention group for 3 cycles. Standard doses of gemcitabine and nab-paclitaxel are adopted. Surgical resection will be performed after neoadjuvant chemotherapy.<br>|
| Experimental: Group B of neoadjuvant chemoradiotherapy<br>Neoadjuvant gemcitabine plus nab-paclitaxel with SBRT is used in this group. Intravenous administration of gemcitabine (1000mg/m2) and nab-paclitaxel (125 mg/m2) are initiated on day 1, 8 and 15 during each 4-week cycle, which will repeat for 3 cycles. After completion of the whole chemotherapy, patients will first receive PET-CT to exclude distant metastases and then undergo SBRT. The prescribed dose is 7.5-8Gy/f for 5 fractions. Dose constraints of normal tissues are referred to the American Association of Physicists in Medicine guidelines in TG-101. And surgical resection is performed 3 weeks after SBRT. | Drug: Neoadjuvant gemcitabine plus nab-paclitaxel with SBRT<br>* Neoadjuvant gemcitabine plus nab-paclitaxel with SBRT is used in the intervention group for 3 cycles. Standard doses of gemcitabine and nab-paclitaxel are adopted. The radiation dose of SBRT is 7.5-8Gy/f for 5 fractions. Surgical resection will be performed 3 weeks after SBRT.<br>|
| Experimental: Group C of neoadjuvant chemoradiotherapy<br>Neoadjuvant S-1 plus nab-paclitaxel with SBRT is used in this group. Intravenous administration of nab-paclitaxel (125 mg/m2) is initiated on day 1, 8 and 15 during each 4-week cycle, which will repeat for 3 cycles. And S-1 is orally administrated at a dose of 80 mg/m2 for 18 days followed by a 10-day rest during each 4-week cycle, which aslo continues for 3 cycles. After completion of the whole chemotherapy, patients will first receive PET-CT to exclude distant metastases and then undergo SBRT. The prescribed dose is 7.5-8Gy/f for 5 fractions. Dose constraints of normal tissues are referred to the American Association of Physicists in Medicine guidelines in TG-101. And surgical resection is performed 3 weeks after SBRT. | Drug: Neoadjuvant S-1 plus nab-paclitaxel with SBRT<br>* Neoadjuvant S-1 plus nab-paclitaxel with SBRT is used in the intervention group for 3 cycles. Standard doses of gemcitabine and nab-paclitaxel are adopted. The radiation dose of SBRT is 7.5-8Gy/f for 5 fractions. Surgical resection will be performed 3 weeks after SBRT.<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall time | The time between operation and the death of patients | From date of randomization until the date of death from any cause, whichever came first, assessed up to 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease free time | The time between operation and the relapse or metastasis of tumors | From date of randomization until the date of first documented progression or metastasis, assessed up to 12 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
pancreatic cancer, neoadjuvant chemotherapy, SBRT