A Pilot Study to Evaluate the Safety of a 3 Weeks Sitagliptin Treatment in HCC Patients Undergoing Liver Resection

NCT02650427 | Completed Phase 1 DMC

• 2 other identifiers: C15-412015-002968-17
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

Brief Summary

Boosting of tumor cell killing by cytotoxic lymphocytes may be a promising means to enhance anti-tumor immunity. Prior studies demonstrated that tumor infiltration by cytotoxic lymphocytes correlates with control of tumor growth and is associated with an improved prognosis in cancer patients. Trafficking of activated lymphocytes is a tightly regulated mechanism and the specific nature of the chemokine milieu is a crucial determinant for permitting T cell entry into the tumor microenvironment. CXCL10 is an interferon-inducible chemokine particularly important for the recruitment of activated T, and it has been shown to enhance anti-tumor responses through its action on cytotoxic T cells (e.g., glioblastoma, colorectal adenocarcinoma and lung carcinoma). Additionally, roles for CXCL10 as an anti-tumor effector include its ability to chemo-attract NK cells into sites of inflammation, and its ability to inhibit development of new vasculature and induce the regression of newly formed vessels. Adding a layer of complexity, the function of CXCL10 can be regulated by dipeptidylpeptidase IV (DPPIV), leading to the formation of a dominant negative, antagonist form of the chemokine. This was initially demonstrated in vitro, and recent work has provided convincing in vivo evidence that antagonist forms of CXCL10 regulate lymphocyte trafficking. The main goal of this protocol is to evaluate the tolerance of sitagliptin treatment in HCC patients, and secondary DPPIV inhibitors as a strategy for protecting CXCL10 chemokine agonist activity as a means to enhance tumor regression.

Conditions

Hepato Carcinoma

Outcome Measures

Primary Outcomes (1)

• Safety (Number of adverse events. Toxicity grade > 3)

  After Day 0 until the end of the trial, i.e. a duration of 3 weeks +/- 7 days for each patient

Secondary Outcomes (4)

• DPPIV Activity

  Baseline; week 1, 3 of sitagliptin therapy , 3 days after end of sitagliptin therapy

• CXCL10 truncation

  Baseline; week 1, 3 of sitgaliptin therapy, 3 days after end of sitagliptin therapy

• Immune cells trafficking

  Baseline; week 1, 3 of sitagliptin therapy, 3 days after end of sitagliptin therapy

• Infiltration of leucocytes in tumor tissue

  Baseline, week 3 of sitagliptin therapy

Study Arms (1)

DPPIV Inhibition

EXPERIMENTAL

The study will include 3 weeks administration (± 7 days) of sitagliptin as monotherapy (taken orally). The study will use 3 doses: the first five patients will receive 100 mg/day, the next five 200 mg/day and the last five patients 600 mg/day. During this time, arrangements will be made for surgical resection, as per the standard of care treatment of patients. Blood samples will be obtained for immunology studies. The study will end one week after surgery. Patients will continue their treatment for HCC as prescribed by the clinician.

Drug: Sitagliptin

Interventions

Sitagliptin DRUG

100mg or 200mg or 600mg, daily for 3 weeks ± 7 days

Also known as: Januvia

DPPIV Inhibition

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• HCC based on medical imaging with indication of liver resection and without contra-indication of preoperative liver biopsy.
• Minor resection not exceeding 2 liver segments
• No cirrhosis or cirrhosis with a Child-Pugh Score Class A. Note: this score is used worldwide to assess liver function in cirrhosis.
• Informed consent must be obtained for all subjects prior to study entry.
• Patients affiliated to health policy insurance.

You may not qualify if:

• Presence of HIV Infection.
• Presence of renal impairment (CrCl \<60 ml / min).
• Liver function compromised (Child Pugh B, MELD score \> 9)
• Indirect sign of portal hypertension (Oesophagal Varices, splenomegaly, platelet count less than 100.000)
• A need for major hepatic resection (more than 2 segments)
• Taking digoxin (digitalis) within 6 months of starting treatment.
• History of severe hypersensitivity reaction (such as anaphylactic shock or angioedema) to sitagliptin.
• Patients with diabetes.
• Pregnant or absence of an effective contraception for women.
• A person deprived of liberty by judicial or administrative decision, person subject to a legal protection measure.
• Living conditions suggesting an inability to track all scheduled visits by the protocol.
• Life expectancy less than 3 months.

Sponsors & Collaborators

• Institut National de la Santé Et de la Recherche Médicale, France: lead

Study Sites (1)

Pitié-Salpêtrière Hospital

Paris, 75013, France

Location

Related Links

• This paper reports results of this study

MeSH Terms

Interventions

Sitagliptin Phosphate

Intervention Hierarchy (Ancestors)

Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrazines

Study Officials

• Olivier SCATTON

  Pitié-Salpêtrière Hospital, Paris, France

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 22, 2015
• First Posted: January 8, 2016
• Study Start: February 1, 2016
• Primary Completion: September 1, 2018
• Study Completion: September 1, 2018
• Last Updated: September 2, 2025

Record last verified: 2018-10

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)