A Phase 2, Single Arm Study of Cabozantinib in Patients With Hepatocellular Carcinoma Who Have Received Prior Atezolizumab and Bevacizumab
Overview
- Phase
- Phase 2
- Intervention
- Cabozantinib
- Conditions
- Hepatocellular Carcinoma Non-resectable
- Sponsor
- Chulalongkorn University
- Enrollment
- 40
- Primary Endpoint
- Disease control rate (DCR) per RECIST 1.1 at 4th month
- Status
- Not yet recruiting
- Last Updated
- last year
Overview
Brief Summary
Hepatocellular carcinoma (HCC) is the most common liver cancer and a leading cancer death worldwide. Currently, atezolizumab and bevacizumab combination is the standard of care for patients with advanced HCC. There have not been proven therapy for patients with advanced HCC previously treated with atezolizumab and bevacizumab. Cabozantinib is a proven therapy for patients with advanced HCC previously treated with sorafenib. The study aims to demonstrate the efficacy and safety of cabozantinib in patients with advanced previously treated with atezolziumab and bevacizumab. It is a multi-center single-arm study which all participants will receive cabozantinib. Participants will continue cabozantinib until. disease progression or unacceptable toxicities.
Detailed Description
Currently, atezolizumab and bevacizumab combination is the standard of care for patients with advanced HCC. There have not been proven therapy for patients with advanced HCC previously treated with atezolizumab and bevacizumab. Cabozantinib is a proven therapy for patients with advanced HCC previously treated with sorafenib. The study aims to demonstrate the efficacy and safety of cabozantinib in patients with advanced previously treated with atezolziumab and bevacizumab. This is a phase II, single-arm, multi-center trial which all participants will receive cabozantinib. Eligible patients will provide informed consent to participate the trial. The study will enroll 40 patients. All participants will receive cabozantinib until disease progression or unacceptable toxicities. Efficacy assessment will be performed with CT scan or MRI every 8 weeks. Clinical assessments and laboratory tests will be scheduled every 2-4 weeks for safety assessments.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Radiological, histological or cytological diagnosis of HCC
- •The subject has disease that is not amenable to a curative treatment approach (eg, transplant, surgery, radiofrequency ablation)
- •Received prior atezolizumab and bevacizumab
- •Progression following atezolizumab and bevacizumab treatment for advanced HCC
- •Recovery to ≤ Grade 1 from toxicities related to any prior treatments, unless the adverse events are clinically nonsignificant and/or stable on supportive therapy
- •Age ≥ 18 years old on the day of consent
- •ECOG performance status of 0 or 1
- •Adequate hematologic function, based upon meeting the following laboratory criteria within 7 days before enrollment:
- •absolute neutrophil count (ANC) ≥ 1200/mm3 (≥ 1.2 x 109/L)
- •platelets ≥ 60,000/mm3 (≥ 60 x 109/L)
Exclusion Criteria
- •• Fibrolamellar carcinoma or mixed hepatocellular cholangiocarcinoma
- •Receipt of more than one prior systemic therapy for advanced HCC. Additional prior systemic therapies used as adjuvant or local therapy are allowed.
- •Any type of anticancer agent (including investigational) within 2 weeks before enrollment
- •Radiation therapy within 4 weeks (2 weeks for radiation for bone metastases) or radionuclide treatment (eg, I-131 or Y-90) within 6 weeks of enrollment. Subject is excluded if there are any clinically relevant ongoing complications from prior radiation therapy.
- •Prior cabozantinib treatment
- •Known brain metastases or cranial epidural disease unless adequately treated with radiotherapy and/or surgery (including radiosurgery) and stable for at least 3 months before enrollment. Eligible subjects must be without corticosteroid treatment at the time of enrollment.
- •Concomitant anticoagulation, at therapeutic doses, with anticoagulants such as warfarin or warfarin-related agents, low molecular weight heparin (LMWH), thrombin or coagulation factor X (FXa) inhibitors, or antiplatelet agents (eg, clopidogrel). Low-dose aspirin for cardioprotection (per local applicable guidelines), low-dose warfarin (≤ 1 mg/day), and low-dose LMWH are permitted.
- •The subject has uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions:
- •Cardiovascular disorders including
- •Symptomatic congestive heart failure, unstable angina pectoris, or serious cardiac arrhythmias
Arms & Interventions
cabozantinib
Open-labelled
Intervention: Cabozantinib
Outcomes
Primary Outcomes
Disease control rate (DCR) per RECIST 1.1 at 4th month
Time Frame: 4th month of treatment
Proportion of participants with stable disease, partial response and complete response at 4th month of cabozantinib treatment based on RECIST 1.1
Secondary Outcomes
- Overall survival (OS)(Time from treatment initiation to patient death, assessed up to 36 months)
- Objective response rate (ORR) per RECIST 1.1 at 4th month(4th month of treatment)
- Progression-free survival (PFS) per RECIST 1.1(Time from treatment initiation to documented disease progression per RECIST 1.1 or death, whichever came first, assessed up to 24 months)