A Phase 2, Single Arm Study of Cabozantinib in Patients With Hepatocellular Carcinoma Who Have Received Prior Atezolizumab and Bevacizumab

NCT06535737 | Not Yet Recruiting Phase 2

• 1 other identifier: onco-059/67
• Study Type: interventional
• Target: 40
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Hepatocellular Carcinoma Non-resectable

Keywords

Hepatocellular carcinoma; Cabozantinib

Outcome Measures

Primary Outcomes (1)

• Disease control rate (DCR) per RECIST 1.1 at 4th month

  Proportion of participants with stable disease, partial response and complete response at 4th month of cabozantinib treatment based on RECIST 1.1

  4th month of treatment

Secondary Outcomes (3)

• 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

• Overall survival (OS)

  Time from treatment initiation to patient death, assessed up to 36 months

Study Arms (1)

cabozantinib

EXPERIMENTAL

Open-labelled

Drug: Cabozantinib

Interventions

Cabozantinib DRUG

Cabozantinib (Cabometyx) 60, 40 and 20 mg

cabozantinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)
• hemoglobin ≥ 8 g/dL (≥ 80 g/L)
• Adequate renal function, based upon meeting the following laboratory criteria within 7 days before enrollment:
• serum creatinine ≤ 1.5 × upper limit of normal or calculated creatinine clearance ≥ 40 mL/min (using the Cockroft-Gault equation: (140 - age) x weight (kg)/(serum creatinine × 72 \[mg/dL\]) for males. (For females multiply by 0.85.) AND
• urine protein/creatinine ratio (UPCR) ≤ 1 mg/mg (≤ 113.1 mg/mmol) or 24-hour urine protein \< 1g
• Child-Pugh Score of A or B7

You may not qualify if:

• 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
• Uncontrolled hypertension defined as sustained BP \> 150 mm Hg systolic, or \> 100 mm Hg diastolic despite optimal antihypertensive treatment
• Stroke (including TIA), myocardial infarction, or other ischemic event within 6 months before enrollment
• Thromboembolic event within 3 months before enrollment. Subjects with thromboses of portal/hepatic vasculature attributed to underlying liver disease and/or liver tumor are eligible
• o Gastrointestinal (GI) disorders including those associated with a high risk of perforation or fistula formation:
• Tumors invading the GI tract, active peptic ulcer disease, inflammatory bowel disease, diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis, acute pancreatitis or acute obstruction of the pancreatic duct or common bile duct, or gastric outlet obstruction

Sponsors & Collaborators

• Chulalongkorn University: lead
• Mahidol University: collaborator

Related Publications (15)

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MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

cabozantinib

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Study Officials

• Suebpong Tanasanvimon, M.D.

  Chulalongkorn University

  STUDY CHAIR

• Nuttapong Ngamphaiboon, M.D.

  Marisol University

  PRINCIPAL INVESTIGATOR

• Krittaya Korphaisarn, M.D.

  Mahidol University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Suebpong Tanasanvimon, M.D.

CONTACT

+666494000; surbpong@yahoo.com

Nattaya Teeyapan, M.D.

CONTACT

+666494000; nattaya.te@chula.ac.th

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 24, 2024
• First Posted: August 2, 2024
• Study Start: August 1, 2024
• Primary Completion: July 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: August 2, 2024

Record last verified: 2024-07