Phase II Single Arm Study of Tremelimumab and Durvalumab (MEDI4736) (T300+D) in Advanced Hepatocellular Carcinomas with Child-Pugh-B Cirrhosis (STRIDE in CP-B)
This is a single-arm, phase II study of patients with advanced liver cancer or hepatocellular carcinoma (HCC) who are eligible for first-line treatment with T300+D. The invesitgators hypothesize that T300+D will be safe and tolerated in CP-B patients with HCC. HCC mostly affects disadvantaged populations with higher rates among racial/ethnic minorities, who are often not included in clinical trials (i.e., Hispanics, Blacks, underserved, low socioeconomic status) and present with more severe disease. Given there is not much data in the US patient cohort, this study provides a chance to gain that knowledge.
• Patients diagnosed with HCC based on pathologic diagnosis from biopsy or radiographic diagnosis on CT liver or MRI liver (i.e., Barcelona Clinic Liver Cancer (BCLC) stage B and not candidate for locoregional therapies or BCLC stage C)10
• Patients with Child-Pugh-B7 or -B8 liver cirrhosis11
• ECOG performance status score 0-1
• Patients with Hepatitis B Virus (HBV) infection are required to receive effective antiviral therapy and have a viral load less than 500 IU/mL at screening; antiviral therapy is not required for patients with Hepatitis C Virus (HCV) infection.
• Adequate organ and bone marrow function:
∙ Absolute neutrophil counts ≥1000/uL
‣ Platelets ≥60 × 100/uL
‣ Hemoglobin ≥8.0 g/dL
‣ ALT and AST ≤5× upper limit of normal each
‣ Bilirubin ≤3 mg/dL,
‣ International normalized ratio (INR) ≤2.3 or prothrombin time ≤6 seconds above control)
‣ Measured creatinine clearance (CL) \>40 mL/min or Calculated creatinine clearance CL\>40 mL/min by the Cockcroft-Gault formula (Cockcroft and Gault 1976) or by 24-hour urine collection for determination of creatinine clearance:
• Males:
• Creatinine CL (mL/min)=Weight (kg) x (140 - Age) /72 x serum creatinine (mg/dL)
• Females:
• Creatinine CL (mL/min)=Weight (kg) x (140 - Age) x 0.85 /72 x serum creatinine (mg/dL)
• Body weight \>30 kilogram (kg)
• Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol. Written informed consent and any locally required authorization (e.g., Health Insurance Portability and Accountability Act in the US) obtained from the patient/legal representative prior to performing any protocol-related procedures, including screening evaluations.
• Age \>18 years at time of study entry or adult male or female (according to age of majority as defined as ≥18 years)
• Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.
⁃ Must have a life expectancy of at least 12 weeks.
⁃ At least 1 lesion, not previously irradiated, that qualifies as a RECIST 1.1 target lesion (TL) at baseline.