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

Study Purpose

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.

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

 No
Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.


An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.


Searching Both is inclusive of interventional and observational studies.

 Interventional
Eligible Ages 18 Years and Over
Gender All
More Inclusion & Exclusion Criteria

Inclusion Criteria:

  • - Patients with 18 years old the day of inclusion.
  • - For women, a negative blood pregnancy test before inclusion is necessary.
Note: this test will be done only to women of childbearing age and non menopausal.
  • - 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.

Exclusion Criteria:

  • - 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.

Trial Details

Trial ID:

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.

 NCT02650427
Phase

Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

 Phase 1
Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

 Institut National de la Santé Et de la Recherche Médicale, France
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

 Olivier SCATTON
Principal Investigator Affiliation Pitié-Salpêtrière Hospital, Paris, France
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

 Other
Overall Status Completed
Countries France
Conditions

The disease, disorder, syndrome, illness, or injury that is being studied.

 Hepato Carcinoma
Additional Details

The study will be conducted in 15 patients. Patient selection will be made based on medical records during a weekly staff meeting. After collection of informed consent, the patients will undergo a biopsy of the tumor and of the not-tumoral liver and 2-4 weeks later HCC resection. The study will include a phase of 3 weeks [± 7 days] administration of sitagliptin as monotherapy (taken orally) after liver biopsy and before HCC resection. The window of ± 7 days is deliberately wide to take in account the variable arrangements made for surgical resection. Nevertheless we will make our efforts to focus on a three weeks regimen. Three doses of sitagliptin will be used: 1) 100mg/day (dose recommended in the SmCP), 2) 200mg/day and 3) 600mg/day; with 5 patients in each group. Arrangements will be made for surgical resection upon standard care. Blood samples will be obtained for immunology studies at each visit. The study will end one week after surgery (or less if the state of health of the patient does not require to stay longer in the hospital). Patients will continue their treatment for HCC as prescribed by the clinician.

Arms & Interventions

Arms

Experimental: DPPIV Inhibition

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.

Interventions

Drug: - Sitagliptin

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

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

International Sites

Pitié-Salpêtrière Hospital, Paris, France

Status

Address

Pitié-Salpêtrière Hospital

Paris, , 75013

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