Nab-paclitaxel Plus S-1(AS) Versus Nab-paclitaxel Plus Gemcitabine(AG) in Patients With Advanced Pancreatic Cancer

Study Overview
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Brief Summary
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This is a randomized phase II trial comparing the first-line treatment with nab-paclitaxel plus S-1(AS) and nab-paclitaxel plus gemcitabine(AG) in advanced pancreatic ductal adenocarcinoma (PDA) with primary tumor nonexcision in Chinese patients.

Detailed Description
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Advanced pancreatic ductal adenocarcinoma (PDAC) is an aggressive and chemo-resistant disease with extremely low 5-year survival rate. Gemcitabine has been the cornerstone of metastatic PDAC treatment for more than a decade , although survival benefit was very poor. Nab-paclitaxel added to gemcitabine has showed improving survival and overall response rate vs gemcitabine alone in metastatic PDAC first-line treatment in the MPACT phaseIII study, which represents one of the standards of care in advanced PDAC therapy. S-1 is an oral 5-fluorouracil (5-FU) prodrug, and shown to be non-inferior to gemcitabine on OS for unresectable pancreatic cancer. Meanwhile, adjuvant chemotherapy with S-1 monotherapy was found to significant prolong survival of pancreatic cancer patients when compared with gemcitabine. This study is to explore the efficacy and safety of nab-paclitaxel plus S-1(AS) and nab-paclitaxel plus gemcitabine(AG) as first-line treatment in advanced pancreatic ductal adenocarcinoma (PDA) with primary tumor nonexcision in Chinese patients.

Official Title
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Phase II Trial Comparing Nab-paclitaxel Plus S-1 Versus Nab-paclitaxel Plus Gemcitabine in First-line Treatment of Patients With Advanced Pancreatic Cancer

Conditions
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Pancreatic Cancer

Intervention / Treatment
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* Drug: nanoparticle albumin-bound paclitaxel
* Drug: S1
* Drug: Gemcitabine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed informed-consent form. Age no less than 18 years. Histologically confirmed locally advanced or metastatic pancreatic ductal adenocarcinoma, with RECIST measurable lesions. Eastern Cooperative Oncology Group (ECOG) 0-1 with life expectation of no less than 12 weeks. Patients must have received no previous chemotherapy or investigational therapy for the treatment of locally advanced or metastatic disease. At least 4 weeks since completion of the last operation except for diagnostic biopsy. At least 4 weeks since completion of radiotherapy to lesions. Not suitable for local treatment. Adequate liver/bone marrow function. Human Chorionic Gonadotropin (HCG) test negative for female with contraception measure until 3 months after study end. Compliant, and can be followed up regularly. Exclusion Criteria: Received chemotherapy or investigational therapy for the treatment of locally advanced or metastatic disease. Pregnant or breast-feeding female, or not willing to take contraception measures during study. Serious infection requiring antibiotics intervention during recruitment. Allergic to study drug. More than grade 1 neuropathy. Uncontrolled brain metastasis or mental illness. Congestive heart failure, uncontrolled cardiac arrhythmia, etc. Other malignancy within 5 years. Can't be followed up or obey protocol. Ineligible by the discretion of the investigator.

Ages Eligible for Study
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Minimum Age: 18 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: AS：Nanoparticle albumin-bound paclitaxel，S-1<br>Nanoparticle albumin-bound paclitaxel is given at 125 mg/m2 intravenously on day 1 of each 14 day cycle. S-1 is orally administered (BSA<1.25m2, 40mg bid, 1.25m2≤BSA≤1.5m2, 50mg bid, BSA>1.5m2, 60mg bid) on day 1-7 of each 14 day cycle. | Drug: nanoparticle albumin-bound paclitaxel<br>* Nanoparticle albumin-bound paclitaxel is given at 125 mg/m2 intravenously on day 1 of each 14 day cycle or day 1 and 8 of 21 day cycle.<br>* Other names: ABI-007;Drug: S1<br>* S-1 is orally administered (BSA<1.25m2, 40mg bid, 1.25m2≤BSA≤1.5m2, 50mg bid, BSA>1.5m2, 60mg bid) on day 1-7 of each 14 day cycle.<br>|
| Active Comparator: AG：Nanoparticle albumin-bound paclitaxel，Gemcitabine<br>Nanoparticle albumin-bound paclitaxel is given at 125 mg/m2 intravenously on day 1 and 8 of each 21 day cycle. Gemcitabine is given at 1000mg/m2 intravenously on day 1 and 8 of each 21 day cycle. | Drug: nanoparticle albumin-bound paclitaxel<br>* Nanoparticle albumin-bound paclitaxel is given at 125 mg/m2 intravenously on day 1 of each 14 day cycle or day 1 and 8 of 21 day cycle.<br>* Other names: ABI-007;Drug: Gemcitabine<br>* Gemcitabine is given at 1000mg/m2 intravenously on d1 and 8 of each 21 day cycle.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate | Percentage of patients who achieve partial response (PR) or complete response (CR) based on Response Evaluation Criteria In Solid Tumors (RECIST)(every 3 cycles in AS or every 2 cycles in AG). | From date of first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate of primary tumor | Percentage of patients who achieve partial response (PR) or complete response (CR) based on Response Evaluation Criteria In Solid Tumors (RECIST)(every 3 cycles in AS or every 2 cycles in AG). | From date of first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months | 
| Progression-free survival | Measure of time from study treatment to disease progression or death. | up to 15 months | 
| Overall survival | Measure of time from study treatment to patient's death or lost to follow-up. | up to 2 years | 
| Disease control rate | The sum of rates of partial response, complete response and steady disease based on Response Evaluation Criteria In Solid Tumors (RECIST). | From date of first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months | 
| The incidence of treatment related emergent adverse events（Safety and Tolerance） | Adverse reactions evaluation is based on the National Cancer Institute adverse event General terminology Standard [CTCAE] 4.0 version | Until 28 days after the deadline of enrollment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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advanced pancreatic cancer, nanoparticle albumin-bound paclitaxel, S-1, gemcitabine