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.
Patients who are candidates for curative treatments
History of uncontrolled hepatic encephalopathy in the past 6 months; patients who are stable on medical therapy are eligible.
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.
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.
Single group
Tremelimumab
DrugPriming dose of tremelimumab 300 mg IV once (Cycle 1, Day 1 only)
Durvalumab
DrugDurvalumab 1500 mg IV on Day 1 of each 4-week cycle.
Grade 3 or Higher Treatment Related Treatment Emergent-Adverse Events (TRTE-AEs)
The number and grade 1-5 of all adverse events will be documented according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) v5.0; measured at baseline, each cycle, and up to 90 days after treatment discontinued. Grade 3 and higher TRTE-AEs will be reported for this outcome.
Objective Response Rate (ORR)
ORR, complete and partial response, confirmed and unconfirmed as defined by Response evaluation criteria in solid tumors (RECIST) v1.1.9. ORR, complete and partial response, confirmed and unconfirmed) as defined by RECIST v1.1.9. RECIST version 1.1 RECIST is used as tumor response criteria in most trials of solid tumors in general. RECIST1. 1 uses unidimensional diameters of target lesions and the sum of measurements of all target lesions as a quantitative measure of tumor burden.
Progression Free Survival (PFS)
Measured from the date of registration until disease progression, symptomatic deterioration, or death.
Overall Survival (OS)
Measured from date of registration until death
Albumin-Bilirubin (ALBI) grade
Albumin-bilirubin (ALBI) grade is a tool that assesses liver function by combining serum albumin and bilirubin levels. It can be used to predict the prognosis of patients with liver cirrhosis and hepatocellular carcinoma, and has been shown to be more accurate than the Child-Pugh score. ALBI grade can also be used to predict survival for patients treated with radioembolization (RE), and as a prognostic indicator for cancer patients receiving chemotherapy. A calculator is used to generate the score. Based on the score, patients are graded between grade 1 (lowest mortality risk, ALBI score ≤2.60) and grade 3 the highest mortality risk (score \>-1.39).
European Organisation For Research and Treatment of Cancer (EORTC)- Quality of Life Questionnaire (QLC)
A 30-item self-administered questionnaire with 9 multiple-item scales: 5 scales that assess aspects of functioning (physical, role, cognitive, emotional, and social), 3 symptom scales (fatigue, pain, and nausea/vomiting), and a global measure of health status/QOL scale. There are 5 single-item measures assessing additional symptoms commonly reported by cancer patients (dyspnea, loss of appetite, insomnia, constipation, and diarrhea) and 1 item concerning the perceived financial impact of the disease. All but 2 questions have 4-point scales: "Not at all," "A little," "Quite a bit," and "Very much". The 2 questions concerning global health status and QOL have 7-point scales with ratings ranging from "Very poor" to "Excellent". For each of the 15 domains (9 multiple item scales and 6 single-item scales), final scores are transformed such that they range from 0 to 100, where higher scores indicate greater functioning, greater health related quality of life, or lower level of symptoms.
EORTC QLQ-HCC18 (18-item hepatocellular cancer health-related quality of life questionnaire)
The EORTC QLQ-HCC18 module is an 18-item self-administered questionnaire (Appendix) developed and validated specifically for HCC). There are 5 multiple-item symptom scales (fatigue \[3 items\], jaundice \[2 items\], nutrition \[5 items\], pain \[2 items\], and fever \[2 items\]); 2 single-item symptom scales (abdominal swelling and sexual interest); and 1 multiple-item functional scale (body image \[2 items\]). All questions have a 4-point scale: "Not at all," "A little," "Quite a bit," and "Very much". For each of the 8 domains (6 multiple-item scales and 2 single-item scales), final scores are transformed such that they range from 0 to 100, where higher scores indicate greater level of symptoms. All item response scores are converted into 0 to 100 scores; for all scales, a higher score means a worse symptom or a poorer health related quality of life.
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The University of Texas Health Science Center at San Antonio
Lead sponsor
AstraZeneca
Collaborator
