Cabozantinib in Patients With Hepatocellular Carcinoma (ACTION)

NCT04316182 | Completed Phase 2 Results

• 2 other identifiers: ACTION2019-004991-20
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 6

Brief Summary

Cabozantinib, a small molecule directed to vascular endothelial growth factor receptors, MET and AXL, has shown to significantly improve the overall survival (OS) over placebo in the randomized phase 3 CELESTIAL trial in patients who had up to two lines of prior systemic therapy (including sorafenib) with progression on at least one in comparison to patients who received best supportive care. Although cabozantinib shares similar targets with sorafenib/regorafenib, they present different toxicity profile. While the most common grade 3-4 Adverse Events reported for sorafenib were fatigue (4%), diarrhea (8%), hand-foot reaction (8%) and hypertension (2%); the most frequent grade 3-4 Adverse Events for cabozantinib were hand-foot reaction (3.6%), hypertension (3.4%) and elevation of AST (2.6%). In clinical practice, regorafenib, ramucirumab and cabozantinib are approved by European Medicines Agency (EMA) as second-line treatment approved by EMA until now. However, more than 40% of candidate patients to 2nd line do not meet the RESORCE criteria or REACH-2 trial and are only candidates to cabozantinib treatment. However, investigators do not have safety data about those patients who are treated with other treatments than sorafenib in first line neither data about the real impact of sorafenib-intolerant patients according to the RESORCE trial definition. For this reason, investigators propose to explore the role of cabozantinib in patients who were not considered in the CELESTIAL trial.

Conditions

Hepatocellular Carcinoma

Keywords

Hepatocellular Carcinoma; Cabozantinib

Outcome Measures

Primary Outcomes (5)

• Rate of Adverse Events (AE) ≥ Grade 3 (CTCAE 5.0) Excluding Palmar-plantar Erythrodysesthesia

  Percentage of patients with Grade 3 AEs in relation with total number of treated patients

  Up to 18 months

• Rate of Adverse Events

  Percentage of patients with AEs in relation with total number of treated patients

  Up to 18 months

• Rate of Related-AEs

  Percentage of patients with related AEs in relation with total number of treated patients

  Up to 18 months

• Rate of Death Due to Adverse Events

  Percentage of patients who die during treatment due to adverse events in relation with total number of treated patients

  Up to 18 months

• Rate of AEs Leading to Treatment Discontinuation

  Percentage of patients with AEs leading to treatment discontinuation in relation with total number of treated patients

  Up to 18 months

Secondary Outcomes (6)

• Time to Progression (TTP)

  Up to 18 months

• Objective Response Rate (ORR)

  Up to 18 months

• Pattern of Progression

  Up to 18 months

• Overall Survival (OS)

  Up to 18 months

• Post-progression Survival (PPS)

  Up to 18 months

Study Arms (1)

Cabozantinib

EXPERIMENTAL

Cabozantinib at 60 mg/day in monotherapy until symptomatic tumor progression, unacceptable adverse events, patient decision or death

Drug: Cabozantinib

Interventions

Cabozantinib DRUG

Cabozantinib 60 mg/day. Cabozantinib dose will be modified upon development of adverse events.

Also known as: Cabometix

Cabozantinib

Eligibility Criteria

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

You may qualify if:

• Hepatocellular Carcinoma (HCC) diagnosed according to criteria of American Association for the Study of Liver Diseases (AASLD) definition in 2010.
• Intolerant to sorafenib according to RESORCE trial definition or patients who received treatment different to sorafenib as first-Line treatment.
• The subject has disease that is not amenable to a curative treatment approach (eg, transplant, surgery, radiofrequency ablation)
• Recovery to ≤ Grade 1 according to (CTCAE) v.5.0. from toxicities related to any prior treatments, unless the adverse events are clinically non-significant and/or stable on supportive therapy
• Respect the 15 days of first-line treatment washout before starting cabozantinib
• Age ≥ 18 years old on the day of consent
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Adequate hematologic function, based upon meeting the following laboratory criteria within 7 days before starting therapy:
• absolute neutrophil count (ANC) ≥ 1200/mm3 (≥ 1.2 x 10\*9/L)
• platelets ≥ 60,000/mm3 (≥ 60 x 10\*9/L)
• hemoglobin ≥ 8 g/dL (≥ 80 g/L)
• Adequate renal function, based upon meeting the following laboratory criteria within 7 days before starting therapy:
• Serum creatinine ≤ 1.5 × upper limit of normal or calculated creatinine clearance ≥ 40 mL/min (using the Cockcroft-Gault equation) AND
• Urine protein/creatinine ratio (UPCR) ≤ 1 mg/mg (≤ 113.1 mg/mmol) or 24-hour urine protein \< 1 g
• Child-Pugh Score of A

You may not qualify if:

• Fibrolamellar carcinoma or mixed hepatocellular cholangiocarcinoma
• Radiation therapy (eg, I-131 or Y-90) within 4 weeks (2 weeks for radiation for bone metastases or radionuclide treatment within 6 weeks of starting therapy) (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 starting therapy. Eligible subjects must be without corticosteroid treatment at the time of starting therapy.
• 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
• a. Cardiovascular disorders including:
• i. Symptomatic congestive heart failure, unstable angina pectoris, or serious cardiac arrhythmias ii. Uncontrolled hypertension defined as sustained BP \> 150 mm Hg systolic, or 100 mm Hg diastolic despite optimal antihypertensive treatment iii. Stroke (including TIA), myocardial infarction, or another ischemic event within 6 months before starting therapy iv. Thromboembolic event within 3 months before starting therapy. Subjects with thromboses of portal/hepatic vasculature attributed to underlying liver disease and/or liver tumor are eligible
• b. Gastrointestinal (GI) disorders including those associated with a high risk of perforation or fistula formation:
• i. Tumors invading the GI tract, active peptic ulcer disease, inflammatory bowel disease (eg, Crohn's disease), diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis, acute pancreatitis or acute obstruction of the pancreatic duct or common bile duct, or gastric outlet obstruction ii. Abdominal fistula, GI perforation, bowel obstruction, intra-abdominal abscess within 6 months before starting therapy iii. Note: Complete healing of an intra-abdominal abscess must be confirmed prior to starting therapy
• c. Major surgery within 2 months before starting therapy. Complete healing from major surgery must have occurred 1 month before starting therapy. Complete healing from minor surgery (eg, simple excision, tooth extraction) must have occurred at least 7 days before starting therapy. Subjects with clinically relevant complications from prior surgery are not eligible
• d. Cavitating pulmonary lesion(s) or endobronchial disease
• e. Lesion invading a major blood vessel including, but not limited to: pulmonary artery, or aorta. Subjects with lesions invading the portal vasculature are eligible.
• f. Clinically significant bleeding risk including the following within 3 months of starting therapy: 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
• g. Other clinically significant disorders such as:

Sponsors & Collaborators

• Fundacion Clinic per a la Recerca Biomédica: lead
• Apices Soluciones S.L.: collaborator

Study Sites (6)

Hospital Clinic

Barcelona, Spain

Location

Hospital Vall d'Hebron

Barcelona, Spain

Location

Institut Català D'Oncologia - Hospital Duran I Reynals

Barcelona, Spain

Location

Hospital Puerta de Hierro

Madrid, Spain

Location

Hospital Ramon y Cajal

Madrid, Spain

Location

Hospital Central de Asturias

Oviedo, Spain

Location

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

Results Point of Contact

• Title: Juan Luis Sanz (MW)
• Organization: APICES

juanluis.sanz@apices.es

+34 918166804

Study Officials

• Maria Reig, MD

  BCLC group. Liver Unit. Hospital Clinic. Ciberehd

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

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

Model Details: Single Group Assignment

Study Record Dates

• First Submitted: March 18, 2020
• First Posted: March 20, 2020
• Study Start: July 31, 2020
• Primary Completion: February 22, 2023
• Study Completion: February 22, 2023
• Last Updated: March 30, 2025
• Results First Posted: March 30, 2025

Record last verified: 2025-03

Locations

ES (6)