Phase II Trial of Durvalumab (MEDI4736) With/Without Tremelimumab for Advanced Hepatocellular Carcinoma After Palliative Hypofractionated Radiotherapy
This phase II trial studies how well standard of care hypofractionated radiation therapy followed by durvalumab with or without tremelimumab works in treating patients with hepatocellular cancer (liver cancer) that has spread to other places in the body (advanced) and that is growing, spreading, or getting worse (progressing). In some patients, cancer cells and immune cells start to express signals that stop the body's immune system from killing the cancer. New drugs being developed, such as durvalumab and tremelimumab, are designed to target and block these signals and may help increase the immune response to prevent or slow down cancer growth. Hypofractionated radiation therapy delivers higher doses of radiation therapy over a shorter period of time and may help the immune system work even better. Giving durvalumab with or without tremelimumab after radiation therapy may work better than radiation therapy alone in treating patients with liver cancer.
• Histologically-diagnosed HCC with progression during or after prior PD-(L)1 checkpoint inhibitor immunotherapy (e.g., nivolumab and/or pembrolizumab or atezolizumab; prior durvalumab excluded), or without prior PD-(L)1 checkpoint inhibitor immunotherapy.
• a. For patients without prior histologic or cytologic diagnosis, radiographic diagnosis is allowed provided patients meet American Association for the Study of Liver Diseases (AASLD) criteria for radiographic diagnosis.
• At least 1 Response Evaluation Criteria in Solid Tumors (RECIST) 1.1-measurable tumor present which has not received RT or other local therapy prior to enrollment.
• Clinical indication for RT to any site (e.g. painful primary or metastatic tumor, local complication risk such as impending biliary or vascular obstruction).
• Child Pugh score of A, B7, or B8 provided other liver function criteria are met.
• Eastern Cooperative Oncology Group (ECOG) 0 or 1
• Appropriate antiviral therapy for hepatitis B virus (HBV) according to institutional standard of care with HBV deoxyribonucleic acid (DNA) polymerase chain reaction (PCR) \< 2000 IU/mL.
• Adequate organ function as defined below:
‣ Hemoglobin \>= 9.0 g/dL
⁃ Absolute neutrophil count \>= 1,200/microliter (mcL)
⁃ Platelet count \>= 60,000/mcL
⁃ Serum bilirubin =\< 1.5 x institutional upper limit of normal. This will not apply to patients with confirmed Gilbert's syndrome (persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of hemolysis or hepatic pathology), who will be allowed only in consultation with their physician
⁃ Aspartate aminotransferase (AST) =\< 2.5 x institutional upper limit of normal unless liver metastases are present in which case it can be =\< 5 x upper limit of normal (ULN)
⁃ International normalized ratio (INR) \< 1.5
⁃ Creatinine clearance \> 30 mL/min by Cockcroft Gault formula.
• No contraindication to immune checkpoint inhibitor immunotherapy.
• No contraindication to RT.
⁃ Age \>=18 years at time of study entry.
⁃ Life expectancy of \>= 12 weeks.
⁃ Body weight \> 30 kg (66.1 pounds).
⁃ Evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal patients. Women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause. The following age-specific requirements apply:
∙ Women \< 50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution or underwent surgical sterilization (bilateral oophorectomy or hysterectomy)
‣ Women \>= 50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments, had radiation-induced menopause with last menses \> 1 year ago, had chemotherapy-induced menopause with last menses \> 1 year ago, or underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or hysterectomy)
⁃ Women of childbearing potential and men must agree to use adequate contraception from the time of screening through the duration of study participation and for at least 6 months after receiving combination of durvalumab plus tremelimumab and 3 months after last dose of durvalumab.
⁃ 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.
⁃ 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 United States (US) obtained from the patient/legal representative prior to performing any protocol-related procedures, including screening evaluations.