PErioperative CISGEM + Rilvegostomig in High-Risk Resectable Intra Hepatic CholangioCarcinoma

Korábbi kezelés

• Contraindication to immunotherapy: Active or prior documented autoimmune or inflammatory disorders or any severe or uncontrolled systemic disease
• Current or prior use of immunosuppressive medication within 14 days before the first dose of protocol treatment
• Live vaccine administration within 30 days prior to the first dose of study treatment Note: Patients, if enrolled, should not receive live vaccine whilst receiving investigational product and up to 6 months after the last dose of investigational product.
• History of clinically significant arrhythmia, cardiomyopathy of any etiology; symptomatic congestive heart failure (as defined by New York Heart Association class ≥ 3), history of myocardial infarction within the past 6 months. Participation in another clinical study with an investigational product during the last 4 weeks

Más betegség

• Locally advanced disease considered as definitively non resectable
• Persistent toxicities (> grade 2 NCI-CTCAE version 5.0) caused by previous cancer therapy.
• History of allogenic organ transplantation
• Known or suspected allergy or hypersensitivity to any of the study drugs or any of the study drug excipients (cisplatin, gemcitabine and Rilvegostomig)
• Active and untreated infection with hepatitis B and/or hepatitis C Note: Patients with past HBV infection or resolved HBV infection (defined as having a negative HBsAg test and a positive hepatitis B core antigen [HBc] antibody test) are eligible.
• Other active cancer or history of cancer within 2 years, except for carcinoma in situ of the cervix or basal cell or squamous cell skin carcinoma or any other carcinoma in situ, considered cured

Laborértékek

• Cirrhosis with Child Pugh ≥ B7
  • Any history of liver decompensation: hepatic encephalopathy, presence of ascites
  • Presence of clinically significant portal hypertension (platelets counts < 150G/L and/or liver stiffness > 20kPa and/or presence of oesophageal and/or gastric varices)
• Uncontrolled infection with human immunodeficiency virus (HIV). Required conditions for inclusion are as follows: undetectable viral RNA, CD4+ count ≥350 cells/μL no history of AIDS-defining opportunistic infection within the past 12 months, stable condition for at least 4 weeks on the same anti-HIV medications.

Egyéb

• Existence of metastases or distant lymph node involvement considered as metastatic
• Mixed histology (hepatocholangiocarcinoma)
• Pregnant or breastfeeding woman.
• Person deprived of liberty or under guardianship or incapable of giving consent
• Inability to undergo the medical follow-up of the trial for geographical, social or psychological reasons.

• Age ≥ 18 years
• WHO Performance Status 0-1
• Body weight > 30kg
• Histo/cytologically proven intrahepatic cholangiocarcinoma.
• Measurable disease as defined by RECIST 1.1 criteria (Response Evaluation Criteria in Solid Tumors).
• Naive to systemic treatment and loco regional treatment for biliary tract cancer
• At least one of the following high-risk criteria of post resection relapse:
  • Tumor Size ≥ 50 mm and/or multiple nodules
  • cN+
  • Risk of narrow margin (< 10 mm)
  • Macrovascular invasion
• Adequate organ function, as defined by the following:
  • Serum aspartate aminotransferase (AST) and serum alanine aminotransferase (ALT) ≤ 2,5 x Upper Limit of Normal (ULN)
  • Total serum bilirubin ≤ 1.5 ULN This will not apply to patients with confirmed Gilbert's syndrome
  • Prothrombin ratio > 70 % and/or Factor V > 70 % in case of oral anticoagulation therapy
  • Serum albumin ≥ 30 g/L
  • Haemoglobin ≥ 10 g/dl and no transfusion within 4 weeks before inclusion
  • Absolute Neutrophil Count (ANC) ≥ 1.5 G/L
  • Platelets ≥ 150 G/L
• Creatinine clearance ≥ 45 ml/min (calculated by CKD - EPI formula)
• Life expectancy ≥ 3 months
• Female postmenopausal for at least one year or surgically infertile for at least 6 weeks, or highly effective contraception for male and female patients of childbearing potential for the duration of study and for 7 months after the last dose of drug for female and 4 months for male.
• A negative pregnancy test for inclusion for all female patients of child-bearing potential.
• Patient covered by a plan of the French Social Security system.
• Written informed consent obtained from the patient prior to performing any protocol-related procedures
• Patient with available tumor tissue sample for the study or willing to have a biopsy