Hepatocellular CarcinomaPhase 2ACTIONNCT04316182
Cabozantinib in Patients With Hepatocellular Carcinoma (ACTION)
A Phase 2 study testing Cabozantinib in people with Hepatocellular Carcinoma, run by Fundacion Clinic per a la Recerca Biomédica at 6 sites in Spain.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hepatocellular Carcinoma
- What is being tested?
- Cabozantinib
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 6 sitesSpain
- Study dates
- 31 Jul 2020to 22 Feb 2023
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 24Show fewer
- 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
- Total bilirubin ≤ 2 mg/dL (≤ 34.2 μmol/L) within 7 days before starting therapy
- Serum albumin ≥ 2.8 g/dL (≥28 g/L) within 7 days before starting therapy
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 5.0 upper limit of normal (ULN) within 7 days before starting therapy
- Hemoglobin A1c (HbA1c) ≤ 8% within 28 days before starting therapy (if HbA1c results are unavailable [eg, hemoglobin variant], a fasting serum glucose ≤ 160 mg/dL)
- Antiviral therapy per local standard of care if active hepatitis B (HBV) infection
- Capable of understanding and complying with the protocol requirements and signed informed consent
- Sexually active fertile subjects and their partners must agree to use medically accepted methods of contraception (eg, barrier methods, including male condom, female condom, or diaphragm with spermicidal gel) during the course of the study and for 4 months after the last dose of study treatment
- Female subjects of childbearing potential must not be pregnant at screening.
- Subjects must consent to perform a tumor liver biopsy within 4 weeks before starting cabozantinib, allowing the acquisition of a tumor sample for performance of correlative studies.
Who cannot join
- 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
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- Cardiovascular disorders including:
- 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
- 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 (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
- 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
- Cavitating pulmonary lesion(s) or endobronchial disease
- Lesion invading a major blood vessel including, but not limited to: pulmonary artery, or aorta. Subjects with lesions invading the portal vasculature are eligible.
- 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
- 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. Subjects with active hepatitis virus infection controlled with antiviral therapy are eligible.
- Serious non-healing wound/ulcer/bone fracture iii. Malabsorption syndrome iv. Uncompensated/symptomatic hypothyroidism v. Requirement for hemodialysis or peritoneal dialysis vi. History of solid organ transplantation
- Subjects with untreated or incompletely treated varices with bleeding or high risk for bleeding. Subjects treated with adequate endoscopic therapy (according to institutional standards) without any episodes of recurrent GI bleeding requiring transfusion or hospitalization for at least 6 months prior to study entry are eligible.
- Moderate or severe ascites. Note that controlled ascites with stable dose of diuretics in the last month is allowed.
- Corrected QT interval calculated by the Fridericia formula (QTcF) > 500 ms within 7 days before starting therapy
- Inability to swallow tablets
- Previously identified allergy or hypersensitivity to components of the study treatment formulations
- Pregnant or lactating females
- Diagnosis of another malignancy within 2 years before starting therapy, except for superficial skin cancers, or localized, low-grade tumors deemed cured and not treated with systemic therapy
- History of allergy to study drug components.
- Prisoners or subjects who are involuntarily incarcerated
- Subjects who are compulsorily detained for treatment of either a psychiatric or physical (eg. infectious disease) illness
- Inability to comply with restrictions and prohibited activities/treatments.
Trial locations and contacts
6 sites in 1 country.
6 sites in 1 country
Spain6 sites
Hospital Clinic
Barcelona
Hospital Vall d'Hebron
Barcelona
Institut Català D'Oncologia - Hospital Duran I Reynals
Barcelona
Hospital Puerta de Hierro
Madrid
Hospital Ramon y Cajal
Madrid
Hospital Central de Asturias
Oviedo
About this study
Official title: A Phase II triAl of Cabozantinib for hepaTocellular carcInoma Patients intOlerant to Sorafenib Treatment or First Line Treatment Different to sorafeNib. (ACTION Trial)
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%).
Read more
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
- Being tested
- Cabozantinib
- Keywords
- Hepatocellular Carcinoma, Cabozantinib
- Medical subject headings
- Carcinoma, Hepatocellular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CabozantinibDrug
Also called Cabometix
Cabozantinib 60 mg/day. Cabozantinib dose will be modified upon development of adverse events.
| Study group | Role | What they receive |
|---|---|---|
| Cabozantinib | Experimental | Cabozantinib at 60 mg/day in monotherapy until symptomatic tumor progression, unacceptable adverse events, patient decision or death Receives: Drug: Cabozantinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: Up to 18 months
Rate of Adverse Events
Percentage of patients with AEs in relation with total number of treated patients
Measured: Up to 18 months
Rate of Related-AEs
Percentage of patients with related AEs in relation with total number of treated patients
Measured: 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
Measured: 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
Measured: Up to 18 months
Secondary outcomes (6)
Time to Progression (TTP)
Time from the date of start of treatment until the date of objective disease progression or death
Measured: Up to 18 months
Objective Response Rate (ORR)
ORR is defined as the number of subjects with a best overall response of a complete response (CR) or partial response (PR) divided by the number of included patients
Measured: Up to 18 months
Pattern of Progression
Type of progression divided by number of patients
Measured: Up to 18 months
Overall Survival (OS)
Time from the date of start of treatment until the date of death
Measured: Up to 18 months
Post-progression Survival (PPS)
Time from the date of disease progression until the date of death
Measured: Up to 18 months
Rate of Patients Who Develop New Extra-hepatic Spread
Number of subjects who develop new extra-hepatic spread divided by number of included patients
Measured: Up to 18 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Mar 2020
- Study start31 Jul 2020
- Primary completion22 Feb 2023
- Study completion22 Feb 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Hepatocellular CarcinomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Single Group Assignment
- Masking
- None (open label)
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- Fundacion Clinic per a la Recerca Biomédica
- Sponsor type
- University, hospital or other
- Collaborators
- Apices Soluciones S.L.
- Responsible party
- Sponsor
- Investigators
- Maria Reig, MD, Principal investigator, BCLC group. Liver Unit. Hospital Clinic. Ciberehd
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04316182
- Sponsor's protocol ID
- ACTION
- Other IDs
- 2019-004991-20, 2019
- Acronym
- ACTION
- Status last verified
- Mar 2025
- First submitted
- 18 Mar 2020
- Last updated
- 30 Mar 2025
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 30 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II triAl of Cabozantinib for hepaTocellular carcInoma Patients intOlerant to Sorafenib Treatment or First Line Treatment Different to sorafeNib. (ACTION Trial)
- ClinicalTrials.gov ID
- NCT04316182
- Acronym / sponsor ID
- ACTION / ACTION
- Conditions
- Hepatocellular Carcinoma
- Keywords
- Hepatocellular Carcinoma, Cabozantinib
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- Fundacion Clinic per a la Recerca BiomédicaUniversity, hospital or other
- Collaborators
- Apices Soluciones S.L.
- Study start
- 31 Jul 2020 (actual)
- Primary completion
- 22 Feb 2023 (actual)
- Study completion
- 22 Feb 2023 (actual)
- First posted
- 20 Mar 2020 (actual)
- Results
- Posted 30 Mar 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Single Group Assignment
| Arm | Type | Receives |
|---|---|---|
| Cabozantinib | Experimental | Drug: CabozantinibCabozantinib at 60 mg/day in monotherapy until symptomatic tumor progression, unacceptable adverse events, patient decision or death |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (24 listed)
- 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
Key exclusion criteria (28 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CabozantinibAlso: CabometixCabozantinib 60 mg/day. Cabozantinib dose will be modified upon development of adverse events. | Drug | Cabozantinib |
Primary outcome
Rate of Adverse Events (AE) ≥ Grade 3 (CTCAE 5.0) Excluding Palmar-plantar Erythrodysesthesia
Time frame: Up to 18 months
Percentage of patients with Grade 3 AEs in relation with total number of treated patients
Rate of Adverse Events
Time frame: Up to 18 months
Percentage of patients with AEs in relation with total number of treated patients
Rate of Related-AEs
Time frame: Up to 18 months
Percentage of patients with related AEs in relation with total number of treated patients
Rate of Death Due to Adverse Events
Time frame: Up to 18 months
Percentage of patients who die during treatment due to adverse events in relation with total number of treated patients
Rate of AEs Leading to Treatment Discontinuation
Time frame: Up to 18 months
Percentage of patients with AEs leading to treatment discontinuation in relation with total number of treated patients
6 secondary outcomes
Time to Progression (TTP)
Time frame: Up to 18 months
Objective Response Rate (ORR)
Time frame: Up to 18 months
Pattern of Progression
Time frame: Up to 18 months
Overall Survival (OS)
Time frame: Up to 18 months
Post-progression Survival (PPS)
Time frame: Up to 18 months
Rate of Patients Who Develop New Extra-hepatic Spread
Time frame: Up to 18 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Mar 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Maria Reig, MD principal investigator
BCLC group. Liver Unit. Hospital Clinic. Ciberehd
6 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Cabozantinib in people with Hepatocellular Carcinoma, run by Fundacion Clinic per a la Recerca Biomédica at 6 sites in Spain.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 24 inclusion and 28 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 30 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 30 Mar 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Rate of Adverse Events (AE) ≥ Grade 3 (CTCAE 5.0) Excluding Palmar-plantar Erythrodysesthesia (time frame: Up to 18 months). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Mar 2025.