Borderline Resectable Pancreatic Cancer Neoadjuvant Chemoradiotherapy Clinicaltrial-1

Phase 2

Recruiting

• Conditions: Pancreatic Cancer
• Interventions: Drug: Neoadjuvant gemcitabine plus nab-paclitaxel; Drug: Neoadjuvant S-1 plus nab-paclitaxel with SBRT; Drug: Neoadjuvant gemcitabine plus nab-paclitaxel with SBRT

• Registration Number: NCT03777462
• Lead Sponsor: Changhai Hospital

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.

Study Timeline

• Study First Submitted: 2018-12-14
• Study First Submitted QC: 2018-12-14
• Study First Posted: 2018-12-17
• Study Start: 2019-04-01
• Status Verified: 2023-08
• Last Update Submitted: 2023-08-31
• Last Update Posted: 2023-09-01
• Primary Completion: 2023-12-31
• Study Completion: 2023-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 150

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Group A of neoadjuvant chemotherapy	Neoadjuvant gemcitabine plus nab-paclitaxel	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.
Group C of neoadjuvant chemoradiotherapy	Neoadjuvant S-1 plus nab-paclitaxel with SBRT	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.
Group B of neoadjuvant chemoradiotherapy	Neoadjuvant gemcitabine plus nab-paclitaxel with SBRT	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.

Primary Outcome Measures

Name	Time	Method
Overall time	From date of randomization until the date of death from any cause, whichever came first, assessed up to 24 months	The time between operation and the death of patients

Secondary Outcome Measures

Name	Time	Method
Disease free time	From date of randomization until the date of first documented progression or metastasis, assessed up to 12 months	The time between operation and the relapse or metastasis of tumors

Trial Locations

Locations (1)

Changhai Hospital; 🇨🇳 Shanghai, Shanghai, China