A Study to Evaluate the Safety, Tolerability and Efficacy of Cabozantinib in Patients With Hepatocellular Carcinoma and Impaired Liver Function

NCT04454762 | Unknown Phase 2

• 1 other identifier: CaboCHILD
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

This is an prospective, interventional, non-randomized multicenter phase II study to evaluate the safety, tolerability and efficacy of Cabozantinib as a second-line therapy (after one prior systemic therapy) in patients with intermediate to advanced HCC (BCLC B/C) and concomitant impaired liver function CP score B7-8. Subjects who meet all study eligibility criteria will receive Cabozantinib 40 mg daily orally. Subjects will receive Cabozantinib as long as they continue to experience clinical benefit in the opinion of the Investigator or until there is unacceptable toxicity or the need for subsequent systemic anti-cancer treatment or liver directed local anti-cancer therapy. Treatment may continue in this fashion after radiographic progression as long as the Investigator believes that the subject is still receiving clinical benefit from Cabozantinib and that the potential benefit of continuing Cabozantinib outweighs potential risk. In addition, all subjects will be treated with best supportive care. This excludes systemic anti-cancer therapy and liver-directed local anti-cancer therapy.

Conditions

Hepatocellular Carcinoma

Keywords

Hepatocellular carcinoma; HCC; Child-Pugh; cabozantinib

Outcome Measures

Primary Outcomes (6)

• Incidence of Adverse Events (AEs) [Safety and Tolerability]

  An AE is any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants who experience an AE will be presented.

  Through study completion, up to approximately 2 years

• Number of Participants Who Discontinue Study Treatment Due to Adverse Events (AEs) [Safety and Tolerability]

  The number of participants who discontinue study treatment due to an AE will be presented.

  Through study completion, up to approximately 2 years

• ALBI [Safety and Tolerability]

  Assessment of the Albumin-Bilirubin (ALBI) Grade. Grade range 1-3, with 3 indicating greatest severity

  Through study completion, up to approximately 2 years

• ECOG [Safety and Tolerability]

  Eastern Cooperative Oncology Group (ECOG) performance status. Score range 0 (normal activity) to 5 (dead).

  Through study completion, up to approximately 2 years

• Child-Pugh [Safety and Tolerability]

  Used to assess the prognosis of chronic liver disease. Classification of severity of liver disease according to the degree of ascites, total bilirubin and albumin, prothrombin time, and degree of encephalopathy. Each measure is scored 1-3, with 3 indicating greatest severity

  Through study completion, up to approximately 2 years

• Blood pressure [Safety and Tolerability]

  mmHg

  Through study completion, up to approximately 2 years.

Secondary Outcomes (5)

• Overall survival (OS)

  Through study completion, up to approximately 2 years

• Progression-free survival (PFS)

  Through study completion, up to approximately 2 years

• Objective response rate (ORR)

  Through study completion, up to approximately 2 years

• Pharmacokinetics (PK) of Cabozantinib administration.

  6 weeks

• Health-related quality of life (HRQOL)

  Through study completion, up to approximately 2 years

Study Arms (1)

Cabozantinib

EXPERIMENTAL

40 mg cabozantinib oral daily. When dose reduction is necessary, it is recommended to reduce to 20 mg daily.

Drug: Cabozantinib

Interventions

Cabozantinib DRUG

oral administration (40 mg daily, reduced dose 20 mg daily)

Also known as: Cabometyx

Cabozantinib

Eligibility Criteria

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

You may qualify if:

• Written informed consent
• Age ≥ 18
• Histological/cytological or non-invasive (according to EASL/AASLD guidelines) diagnosis of HCC
• Availability of a recent (up to 28 days old) CT/MRI images of thorax and abdomen
• Subject's HCC is not amenable to a curative treatment approach (e.g., transplant, surgery, radiofrequency ablation) corresponding to BCLC classification B/C
• Progression or toxicities following one prior systemic therapy for HCC
• Recovery to ≤ grade 1 from toxicities related to any prior treatments, unless the adverse events are clinically non-significant and/or stable on supportive therapy
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
• 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 Cockcroft-Gault equation)
• Liver function Child-Pugh (CP) score B7-8
• ALBI (albumin-bilirubin) grade 1-2
• Alanine aminotransferase (ALT) and aspartate amino-transferase (AST) \< 7.0 × upper limit of normal (ULN) within 7 days before enrollment
• Antiviral therapy per local standard of care if active hepatitis B (HBV) infection
• Capability to understand and comply with the protocol requirements (e.g. sufficient knowledge of German language to answer the questionnaires, ability to swallow intact tablets).

You may not qualify if:

• Fibrolamellar carcinoma or mixed hepatocellular cholangiocarcinoma
• Receipt of more than 1 prior systemic therapy for advanced HCC. Additional prior systemic therapies used as adjuvant therapy are allowed.
• Any type of anti-cancer agent (including investigational) within 2 weeks before enrollment
• Radiation therapy within 4 weeks (2 weeks for radiation for bone metastases) or radionuclide treatment (e.g., I-131 or Y-90) within 6 weeks of enrollment. Subject cannot be enrolled 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 activated coagulation factor X (FXa) inhibitors, or antiplatelet agents (e.g., 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, instable 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
• 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; abdominal fistula, GI perforation, bowel obstruction, intra-abdominal abscess within 6 months before enrollment, Note: Complete healing of an intra-abdominal abscess must be confirmed prior to enrollment
• Major surgery within 2 months before enrollment. Complete healing from major surgery must have occurred 1 month before enrollment. Complete healing from minor surgery (e.g., simple excision, tooth extraction) must have occurred at least 7 days before enrollment. Subjects with clinically relevant complications from prior surgery are not eligible
• Cavitating pulmonary lesion(s) or endobronchial disease
• Lesion invading a major blood vessel (e.g., pulmonary artery or aorta)
• Clinically significant bleeding risk within 3 months of enrollment including the following: hematuria, hematemesis, hemoptysis of \> 0.5 teaspoon (\> 2.5 mL) of red blood, or other signs indicative of pulmonary hemorrhage, or history of other significant bleeding if not due to reversible external factors
• Other clinically significant disorders such as: Active infection requiring systemic treatment, known infection with human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS)-related illness; serious non-healing wound/ulcer/bone fracture; malabsorption syndrome; uncompensated/symptomatic hypothyroidism; requirement for hemodialysis or peritoneal dialysis; history of solid organ transplantation

Sponsors & Collaborators

• Johannes Gutenberg University Mainz: lead
• Interdisciplinary Center Clinical Trials (IZKS), University Medical Center Mainz: collaborator

Study Sites (1)

Department of Internal Medicine I, Johannes Gutenberg University Mainz

Mainz, 55131, Germany

RECRUITING

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

• Marcus-Alexander Wörns, Prof. MD

  University Medical Center Mainz

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Marcus-Alexander Wörns, Prof. MD

CONTACT

+49 6131 177389; marcus-alexander.woerns@unimedizin-mainz.de

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Senior consultant, Department of Internal Medicine I

Study Record Dates

• First Submitted: June 22, 2020
• First Posted: July 1, 2020
• Study Start: July 22, 2020
• Primary Completion: August 1, 2023
• Study Completion: February 1, 2024
• Last Updated: October 5, 2020

Record last verified: 2020-09

Locations

DE (1)