Sitagliptin Combined With Gemcitabine and Albumin-bound Paclitaxel in PDAC Patients

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to determine the safety and tolerance of sitagliptin combined with gemcitabine and albumin-bound paclitaxel in subjects with locally advanced and metastatic pancreatic ductal adenocarcinoma.

Detailed Description
-----------------
This is a single-institution, prospective, open, one-armed phase Ⅱ clinical trial of sitagliptin combined with gemcitabine and nab-paclitaxel. This study will enroll 30 PDAC patients over 12-15 months.

Official Title
-----------------
The Safety and Tolerance of Sitagliptin Combined With Gemcitabine and Albumin-bound Paclitaxel in Subjects With Locally Advanced and Metastatic Pancreatic Adenocarcinoma: an Open, One-Armed, Single-Center, Phase Ⅱ Study.

Conditions
-----------------
PDAC - Pancreatic Ductal Adenocarcinoma

Intervention / Treatment
-----------------
* Drug: Combination of sitagliptin+ gemcitabine + nab-paclitaxel


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: 1.≥ 18 years old at the time of informed consent 2.Ability to provide written informed consent and HIPAA authorization 3.Untreated locally advanced or metastatic Pancreatic Ductal Adenocarcinoma (PDAC) as defined by National Comprehensive Cancer Network (NCCN) guidelines or, untreated metastatic PDAC (prior adjuvant therapy is permitted if it's been greater than 6 months since completion) 4.Histologically or cytologically confirmed PDAC 5.Confirmed PDAC that is measurable or evaluable per RECIST 1.1 6.Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 7.Gastrointestinal symptoms (nausea, vomiting, and diarrhea) of Grade 1 or less 8.Adequate organ function as defined by: Aspartate transaminase (AST) and alanine transaminase (ALT) levels ≤ 3 x upper limits of normal (ULN) Total bilirubin level ≤ 2 x ULN Creatinine level < 1.7mg/dL For patients with a Body Mass Index (BMI) > 30 kg/m2, lean body weight should be used to calculate the glomerular filtration rate (GFR). Hemoglobin (Hgb) ≥ 90 g/L, Absolute neutrophil count (ANC) ≥ 1.5 x 109/L, Platelets ≥ 80 x 109/L, Acceptable coagulation studies as demonstrated by prothrombin time (PT) within normal limits (+/-15%) unless they are on anticoagulation therapy Life expectancy estimated at ≥ 3 months Exclusion Criteria: With any cancer other than PDAC in recent 5 years; With myocardial infarction; Uncontrolled hypertension (systolic pressure>150mmHg or diastolic pressure>100mmHg after treatment) LVEF<50% History of hemorrhage or thromboembolism in the last 6 months Psychiatric history Pregnant or breastfeeding Interstitial pneumonia or extensive and symptomatic interstitial fibrosis of the lung Autoimmune disease Uncontrolled active infection Other drugs that must be used during the trial may affect the metabolism of the experimental drugs (Sitagliptin, gemcitabine, nab-paclitaxel)

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

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

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

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

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental: Combination of sitagliptin+ gemcitabine + nab-paclitaxel<br>Drug: Sitagliptin Sitagliptin will be administered orally once a day at a dose of 100 mg depending on cohort assignment. Drug: Gemcitabine Gemcitabine will be intravenously administered on Days 1 and 8 of every 21-day cycle at a dose of 1000 mg/m2 depending on cohort assignment. Drug: Nab-Paclitaxel Nab-Paclitaxel will be intravenously administered on Days 1 and 8 of every 28-day cycle at a dose of 125 mg/m2 depending on cohort assignment. | Drug: Combination of sitagliptin+ gemcitabine + nab-paclitaxel<br>* Drug1: Sitagliptin will be administered orally once a day at a dose of 100 mg depending on cohort assignment. Drug2: Gemcitabine will be intravenously administered on Days 1 and 8 of every 21-day cycle at a dose of 1000 mg/m2 depending on cohort assignment. Drug3: Nab-Paclitaxel will be intravenously administered on Days 1 and 8 of every 28-day cycle at a dose of 125 mg/m2 depending on cohort assignment.<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival time | Rrogression-free survival time of PDAC patients | from start of treatment until progression or last known follow up (i.e up to 2 years) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate | Objective Response Rate | from start of treatment until 30 days after treatment discontinuation (i.e up to 2 years) Using RECIST 1.1 | 
| Frequency of adverse events in the safety evaluable population | Frequency of adverse events in the safety evaluable population | Time Frame: from start of treatment until 30 days after treatment discontinuation (i.e up to 2 years) | 
| Median Overall Survival (mOS) of the treated population | Median Overall Survival (mOS) of the treated population | from start of treatment until death or last known follow up (i.e up to 2 years) | 
| Disease control rate (DCR) | Disease control rate (DCR) | 8 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
PDAC, sitagliptin