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)
Overview
- Phase
- Phase 2
- Status
- Recruiting
- Enrollment
- 32
- Locations
- 1
- Primary Endpoint
- Grade 3 or Higher Treatment Related Treatment Emergent-Adverse Events (TRTE-AEs)
Overview
Brief Summary
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.
Detailed 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.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •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,
Exclusion Criteria
- •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.
- •Prior systemic therapy for locally advanced or metastatic HCC
- •Participation in another clinical study with an investigational product during the last 1 month.
- •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.
- •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. \<\<amend as required based on any combination studies with other anticancer agents\>\>
- •Radiotherapy treatment to more than 30% of the bone marrow or with a wide field of radiation within 4 weeks of the first dose of study drug
- •Major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose of IP. Note: Local surgery of isolated lesions for palliative intent is acceptable.
Arms & Interventions
Stride (Single T Regular Interval D) Arm
Tremelimumab dosed once at the beginning of the first cycle, 300mg IV infusion and Durvalumab 1500mg IV dosed with the first dose of Tremelimumab and then once per cycle (every 4 weeks)
Intervention: Tremelimumab (Drug)
Stride (Single T Regular Interval D) Arm
Tremelimumab dosed once at the beginning of the first cycle, 300mg IV infusion and Durvalumab 1500mg IV dosed with the first dose of Tremelimumab and then once per cycle (every 4 weeks)
Intervention: Durvalumab (Drug)
Outcomes
Primary Outcomes
Grade 3 or Higher Treatment Related Treatment Emergent-Adverse Events (TRTE-AEs)
Time Frame: Baseline up to 1 year
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.
Secondary Outcomes
- Progression Free Survival (PFS)(Baseline to 1 year)
- Overall Survival (OS)(Baseline to 1 year)
- Albumin-Bilirubin (ALBI) grade(Baseline to 1 year)
- Objective Response Rate (ORR)(Baseline to 1 year)
Investigators
Sukeshi Patel
Principal Investigator
The University of Texas Health Science Center at San Antonio