Overview
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.
Description
Priming dose of tremelimumab 300 mg IV once (Cycle 1, Day 1 only) with durvalumab 1500 mg IV on Day 1 of each 4-week cycle. Patients will stay on study treatment until evidence of disease progression, unacceptable toxicity, or death.
All eligible patients who consent to this study must have a baseline evaluation (CT or MRI) within 28 days of the start of treatment.
Follow-up: A repeat CT/MRI scan will be performed after 2 cycles of treatment regimen to evaluate response based on RECIST 1.1 criteria (See Appendix for definitions of response).12 Serum tumor marker AFP (every cycle) and CT/MRI scans will be repeated at least every 2 cycles, or 8 weeks, to ensure no progression of disease. Patients will continue treatment until disease progression, unacceptable toxicity, withdrawal of consent by the patient, or decision of physician for patient's best interest. Each patient will be followed for survival for up to one year.
Eligibility
Inclusion Criteria:
1. 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
2. Patients with Child-Pugh-B7 or -B8 liver cirrhosis11
3. ECOG performance status score 0-1
4. 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.
5. Adequate organ and bone marrow function:
1. Absolute neutrophil counts ≥1000/uL
2. Platelets ≥60 × 100/uL
3. Hemoglobin ≥8.0 g/dL
4. ALT and AST ≤5× upper limit of normal each
5. Bilirubin ≤3 mg/dL,
6. International normalized ratio (INR) ≤2.3 or prothrombin time ≤6 seconds above control)
7. 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)
6. Body weight \>30 kilogram (kg)
7. 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.
8. Age \>18 years at time of study entry or adult male or female (according to age of majority as defined as ≥18 years)
9. 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.
10. Must have a life expectancy of at least 12 weeks.
11. At least 1 lesion, not previously irradiated, that qualifies as a RECIST 1.1 target lesion (TL) at baseline.
Exclusion Criteria:
1. Patients who are candidates for curative treatments
2. History of uncontrolled hepatic encephalopathy in the past 6 months; patients who are stable on medical therapy are eligible.
3. Active substance abuse or alcohol abuse at the time of consent or enrollment, which in the opinion of the treating physician would interfere with the safety of the patient and/or adherence to the study protocol.
4. Participants must not have a prior or concurrent malignancy whose natural history or treatment (in the opinion of the treating physician) has the potential to interfere with the safety or efficacy assessment of the investigational regimen.
5. Prior systemic therapy for locally advanced or metastatic HCC
6. Participation in another clinical study with an investigational product during the last 1 month.
7. Concurrent enrolment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study.
8. Any concurrent chemotherapy, IP, biologic, or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for non-cancer-related conditions (e.g., hormone replacement therapy) is acceptable. \<\
