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

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.

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.

Study Overview

• Status: Not yet recruiting
• Conditions: PDAC - Pancreatic Ductal Adenocarcinoma
• Intervention / Treatment: Drug: Combination of sitagliptin+ gemcitabine + nab-paclitaxel

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.

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Jihui Hao, Dr.; Phone Number: 86-022-23340123; Email: haojihui@tjmuch.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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:

1. Aspartate transaminase (AST) and alanine transaminase (ALT) levels ≤ 3 x upper limits of normal (ULN)
2. Total bilirubin level ≤ 2 x ULN
3. 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).
4. 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
5. Life expectancy estimated at ≥ 3 months

Exclusion Criteria:

1. With any cancer other than PDAC in recent 5 years;
2. With myocardial infarction;
3. Uncontrolled hypertension (systolic pressure>150mmHg or diastolic pressure>100mmHg after treatment)
4. LVEF<50%
5. History of hemorrhage or thromboembolism in the last 6 months
6. Psychiatric history
7. Pregnant or breastfeeding
8. Interstitial pneumonia or extensive and symptomatic interstitial fibrosis of the lung
9. Autoimmune disease
10. Uncontrolled active infection
11. Other drugs that must be used during the trial may affect the metabolism of the experimental drugs (Sitagliptin, gemcitabine, nab-paclitaxel)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Experimental: Combination of sitagliptin+ gemcitabine + nab-paclitaxel; 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; 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.

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

Collaborators and Investigators

• Sponsor: Tianjin Medical University Cancer Institute and Hospital
• Investigators: Principal Investigator: Jihui Hao, Dr., Tianjin Medical University affiliated Cancer Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): July 30, 2023
• Primary Completion (Estimated): August 1, 2024
• Study Completion (Estimated): August 1, 2024

Study Registration Dates

• First Submitted: July 9, 2023
• First Submitted That Met QC Criteria: July 9, 2023
• First Posted (Actual): July 17, 2023

Study Record Updates

• Last Update Posted (Actual): July 17, 2023
• Last Update Submitted That Met QC Criteria: July 9, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: sitagliptin; PDAC
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Carcinoma; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Protease Inhibitors; Antineoplastic Agents, Phytogenic; Incretins; Dipeptidyl-Peptidase IV Inhibitors; Paclitaxel; Sitagliptin Phosphate; Gemcitabine
• Other Study ID Numbers: Sitagliptin plus AG-Tianjin

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No