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

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.

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.