Liver CancerPhase 2STRAT-aHCCNCT05622136
Dose-escalation of Regorafenib in Advanced Hepatocellular Carcinoma
A Phase 2 study testing Regorafenib Oral Product in people with Liver Cancer and Hepatocellular Carcinoma, run by Instituto do Cancer do Estado de São Paulo at 1 site in Brazil.
Trial summary
The present protocol (STRAT-aHCC trial) aims to prospectively evaluate the tolerability, quality of life and efficacy of an alternative regimen of regorafenib in patients with advanced hepatocellular carcinoma (HCC) after progression to first-line. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Liver Cancer, Hepatocellular Carcinoma
- What is being tested?
- Regorafenib Oral Product
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 28 participants
- Where
- 1 siteBrazil
- Study dates
- 10 Sep 2023to 15 Dec 2026
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
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
- Age 18 years or older;
- Hepatocellular carcinoma with histological or cytological confirmation or that meet radiological criteria for the diagnosis of HCC21;
- BCLC-B stage not candidate for locoregional treatment or BCLC-C;
- Have been previously treated with at least 1 line of systemic treatment with sorafenib, levantinib, atezolizumab plus bevacizumab or other immunotherapy-based regimen;
- Have received the last dose of first-line systemic treatment between 2 and 6 weeks before starting study treatment;
- Recovery to baseline or ≤ grade 1 from toxicities related to any previous treatments, unless the adverse event is not clinically significant as determined by the investigator (according to the Common Terminology Criteria for Adverse Events (CTCAE) v522);
Show all 16Show fewer
- Not having received previous treatment with regorafenib;
- Child-Pugh A or B7 (in the absence of clinical ascites);
- Measurable disease as defined by the RECIST 1.1 criteria. Target lesions must not have undergone previous local or locoregional treatment (example: ablation, transarterial chemoembolization, radiotherapy or selective internal radiotherapy)
- Performance status: ECOG 0 or 1.
- Adequate hematologic, hepatic and renal functions as defined below:
- Hemoglobin ≥ 8.5 g/dl ii. Absolute neutrophil count ≥ 1,000 /mm3 iii. Platelet count ≥ 50,000 /mm3 iv. Total bilirubin < 2.0 x upper limit of normality (ULN) v. ALT or AST <5 x LSN vi. Creatinine clearance (CrCI) ≥ 30 mL/min (according to Cockroft-Gault formula) vii. Serum albumin ≥ 2.8 mg/dl
- Ability to understand informed consent and comply with the treatment protocol.
- Informed consent form and clarification signed by the patient, impartial witness or legal representative.
- Sexually active patients of childbearing potential and their partners must agree to use highly effective methods of contraception that result in a rate of less than 1% per year when used consistently and correctly throughout the study and 6 months after treatment discontinuation;
- Female participants of childbearing potential cannot be pregnant at screening.
Who cannot join
- Fibrolamellar carcinoma, sarcomatoid HCC or mixed hepatocellular cholangiocarcinoma;
- Previous use of regorafenib;
- Hepatic encephalopathy or medication requirement to control hepatic encephalopathy in the last 60 days before randomization;
- Clinically significant ascites (ie, ascites that requires parcentesis or increased dose of diuretics) within 30 days prior to randomization.
- Patients who have received local therapies (ablation, transarterial chemomebolization or surgery) within 28 days prior to randomization. Radiation treatments with the aim of pain control of bone metastases are allowed.
- Known or suspected brain metastasis or cranial epidural disease unless adequately treated with surgery or radiotherapy and stable for at least 8 weeks from randomization.
Show all 25Show fewer
- Any participant who cannot be submitted neither to computed tomography (CT) nor magnetic resonance imaging (MRI) due to contra-indication to contrast media used.
- The participant has an uncontrolled disease, or a significant complication in the last 28 days of randomization, such as:
- Cardiovascular disorders:
- i. Class III or IV congestive heart failure as defined by the New York Heart Association, unstable angina pectoris, or symptomatic arrhythmias;
- ii. Uncontrolled hypertension (defined as systolic blood pressure greater than 160 mmgHg or diastolic pressure > 95 mmHg despite antihypertensive therapy);
- iii. Stroke, myocardial ischemia, or any ischemic event within the 6-month period prior to randomization;
- Gastrointestinal disorders, including those associated with a high risk of perforation:
- i: active peptic ulcer disease, inflammatory bowel disease, tumors invading the gastrointestinal tract, diverticulitis, cholecystitis, appendicitis, acute pancreatitis and cholangitis;
- ii: Abdominal fistula, gastro-intestinal perforation or abdominal abscess in the last 6 months;
- iii: Esophageal varices that have not been adequately treated or that have been incompletely treated with bleeding or high risk of bleeding. Participants treated with adequate endoscopic therapy with no bleeding in the past 6 months are eligible;
- Clinically detected hematuria, hematemesis, melena, hemoptysis (>2.5 ml) or other clinically significant bleeding within the last 3 months of randomization.
- Cavitating pulmonary lesion or known manifestation of endobronchial disease;
- Other clinically significant diseases, at the discretion of the attending physician.
- Majority surgery within 28 days of randomization. Minor surgeries within 10 days of randomization. Participants must have complete healing of the procedures prior to randomization;
- History of psychiatric illness that is likely to interfere with the ability to understand the study procedures;
- Pregnant or breastfeeding women;
- Inability to swallow pills;
- Known allergies to study drug components;
- Any other known malignancy active at the time of randomization or diagnosis of another malignancy within two years of randomization, except superficial skin carcinomas or low-grade localized tumors considered cured and not treated with systemic therapy.
Trial locations and contacts
1 site in 1 country.
Brazil1 site
ICESP - Instituto do Câncer do Estado de São Paulo
São Paulo, São Paulo, 01246-000
About this study
Official title: Dose-escalation Strategy of Regorafenib in Patients With Advanced Hepatocellular Carcinoma
The present protocol (STRAT-aHCC trial) aims to prospectively evaluate the tolerability, quality of life and efficacy of an alternative regimen of regorafenib in patients with advanced hepatocellular carcinoma (HCC) after progression to first-line. Patients will receive increasing dose of regorafenib in the first 2 treatment cycles (initial dose of 80mg, with weekly increments of 40mg up to 160mg in the first 2 treatment cycles). From the 3rd cycle on, the maximum tolerated dose during the first 2 cycles will be maintained. The maximum tolerated dose will be considered the highest dose in which the patient does not present grade ≥3 adverse events. The primary endpoint is the proportion of evaluable patients completing cycle 4. Radiologic response rate, quality of life, time to progression and overall survival will be evaluated as secondary endpoints.
Read the detailed description
In patients who are refractory to first-line treatment with sorafenib, regorafenib was tested in the phase III RESORCE study. In this study, a standard dose of 160mg/day was used (in cycles of 4 weeks, with 3 weeks on treatment and 1 week off) until tumor progression or limiting toxicity. Regorafenib was superior to placebo with a significant increase in overall survival and became a sequential treatment option.
However, regorafenib is associated with relevant adverse events such as fatigue, hand-foot reaction, diarrhea and hypertension. Such events are more frequent in the first 2 cycles. In the RESORCE trial, 54% of patients had adverse events requiring interruption or dose reduction, and treatment discontinuation was required in 10% of patients. This toxicity profile limits the wide adoption of this drug in clinical practice.
Dose escalation strategies for regorafenib have been evaluated in patients with colorectal cancer and have resulted in better tolerability with comparable efficacy. However, there are no prospective studies with alternative doses of regorafenib in patients with advanced HCC.
The present protocol (STRAT-aHCC trial) aims to prospectively evaluate the tolerability, quality of life and efficacy of an alternative regimen of regorafenib in patients with advanced HCC. Patients will receive increasing dose of regorafenib in the first 2 treatment cycles (initial dose of 80mg, with weekly increments of 40mg up to 160mg in the first 2 treatment cycles - Figure 1). From the 3rd cycle on, the maximum tolerated dose during the first 2 cycles will be maintained. The maximum tolerated dose will be considered the highest dose in which the patient does not present grade ≥3 adverse events. The primary endpoint is the proportion of evaluable patients completing cycle 4. Radiologic response rate, quality of life, time to progression and overall survival will be evaluated as secondary endpoints.
Medical visits will be carried out weekly in the first 2 treatment cycles and every 4 weeks after the 3rd cycle. Laboratory tests will be performed every 2 weeks during the first 2 cycles and every 4 weeks after the 3rd cycle. Response assessment by imaging exams will be performed every 8 weeks. Quality of life assessments will be performed every 4 weeks using the EuroQol EQ-5D-5L7 questionnaire. The planned sample size is 28 patients with an expected duration of 25-30 months.
- Conditions
- Liver Cancer, Hepatocellular Carcinoma
- Being tested
- Regorafenib Oral Product
- Keywords
- Regorafenib, Hepatocellular carcinoma, Dose, Tolerability, Quality of life
- Medical subject headings
- Liver Neoplasms, Carcinoma, Hepatocellular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Regorafenib Oral ProductDrug
Dose escalation strategy
| Study group | Role | What they receive |
|---|---|---|
| Regorafenib | Experimental | Cycles 1 and 2:
* Week 1: 80mg/day
* Week 2: 120mg/day
* Week 3: 160mg/day
* Week 4: off-treatment Cycles 3 on (up to treatment discontinuation)
* Weeks 1 to 3: Maximum dose tolerated daily, defined as the highest dose at which the patient had no adverse events grade ≥3 by CTCAE version 5.0 during cycles 1 and 2.
* Week 4: off treatment
* Dose adjustments may be required. Appendix 11.1 guide dose adjustments. Individual decisions at the occurrence of particular adverse events may be discussed individually within the study team and investigators.
Treatment will be administered until any of the following events occur:
* Both radiological and clinical progression according to definition of mRECIST or clinical deterioration that prevents treatment continuation according to the judgment of the attending physician
* Limiting toxicity as defined by a grade 3 adverse event that does not resolve to grade < 3 within 7 days; adverse event grade 4 or 5.
* Subject decision. Receives: Drug: Regorafenib Oral Product |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of patients who complete 4 cycles of treatment
Measured: 4 months
Secondary outcomes (4)
Proportion of patients with disease control after 4 treatment cycles;
Patients with partial response or stable disease after 4 cycles
Measured: 4 months
Median overall survival: time from treatment initiation to death;
Time from treatment initiation to death
Measured: 5 years
Median progression-free survival: time from treatment initiation to progression or death
Time from treatment initiation to progression or death
Measured: 5 years
Score in the The 5-level EuroQol EQ-5D-5L questionnaire
- 0.532 (worst health state) and 1 (most optimal health state)
Measured: 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Nov 2022
- Study start10 Sep 2023
- Primary completion15 Nov 2026 (estimated)
- Study completion15 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Liver CancerStudies 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
- Sequential
- Masking
- None (open label)
- Enrolment
- 28 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Instituto do Cancer do Estado de São Paulo
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Leonardo Gomes da Fonseca, Instituto do Cancer do Estado de São Paulo
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05622136
- Sponsor's protocol ID
- NP3005
- Acronym
- STRAT-aHCC
- Status last verified
- Mar 2026
- First submitted
- 11 Nov 2022
- Last updated
- 27 Mar 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Dose-escalation Strategy of Regorafenib in Patients With Advanced Hepatocellular Carcinoma
- ClinicalTrials.gov ID
- NCT05622136
- Acronym / sponsor ID
- STRAT-aHCC / NP3005
- Conditions
- Liver Cancer, Hepatocellular Carcinoma
- Keywords
- Regorafenib, Hepatocellular carcinoma, Dose, Tolerability, Quality of life
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 28 participants (estimated)
- Lead sponsor
- Instituto do Cancer do Estado de São PauloUniversity, hospital or other
- Study start
- 10 Sep 2023 (actual)
- Primary completion
- 15 Nov 2026 (estimated)
- Study completion
- 15 Dec 2026 (estimated)
- First posted
- 18 Nov 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The present protocol (STRAT-aHCC trial) aims to prospectively evaluate the tolerability, quality of life and efficacy of an alternative regimen of regorafenib in patients with advanced hepatocellular carcinoma (HCC) after progression to first-line. Patients will receive increasing dose of regorafenib in the first 2 treatment cycles (initial dose of 80mg, with weekly increments of 40mg up to 160mg in the first 2 treatment cycles). From the 3rd cycle on, the maximum tolerated dose during the first 2 cycles will be maintained. The maximum tolerated dose will be considered the highest dose in which the patient does not present grade ≥3 adverse events. The primary endpoint is the proportion of evaluable patients completing cycle 4. Radiologic response rate, quality of life, time to progression and overall survival will be evaluated as secondary endpoints.
Detailed description
In patients who are refractory to first-line treatment with sorafenib, regorafenib was tested in the phase III RESORCE study. In this study, a standard dose of 160mg/day was used (in cycles of 4 weeks, with 3 weeks on treatment and 1 week off) until tumor progression or limiting toxicity. Regorafenib was superior to placebo with a significant increase in overall survival and became a sequential treatment option.
However, regorafenib is associated with relevant adverse events such as fatigue, hand-foot reaction, diarrhea and hypertension. Such events are more frequent in the first 2 cycles. In the RESORCE trial, 54% of patients had adverse events requiring interruption or dose reduction, and treatment discontinuation was required in 10% of patients. This toxicity profile limits the wide adoption of this drug in clinical practice.
Dose escalation strategies for regorafenib have been evaluated in patients with colorectal cancer and have resulted in better tolerability with comparable efficacy. However, there are no prospective studies with alternative doses of regorafenib in patients with advanced HCC.
The present protocol (STRAT-aHCC trial) aims to prospectively evaluate the tolerability, quality of life and efficacy of an alternative regimen of regorafenib in patients with advanced HCC. Patients will receive increasing dose of regorafenib in the first 2 treatment cycles (initial dose of 80mg, with weekly increments of 40mg up to 160mg in the first 2 treatment cycles - Figure 1). From the 3rd cycle on, the maximum tolerated dose during the first 2 cycles will be maintained. The maximum tolerated dose will be considered the highest dose in which the patient does not present grade ≥3 adverse events. The primary endpoint is the proportion of evaluable patients completing cycle 4. Radiologic response rate, quality of life, time to progression and overall survival will be evaluated as secondary endpoints.
Medical visits will be carried out weekly in the first 2 treatment cycles and every 4 weeks after the 3rd cycle. Laboratory tests will be performed every 2 weeks during the first 2 cycles and every 4 weeks after the 3rd cycle. Response assessment by imaging exams will be performed every 8 weeks. Quality of life assessments will be performed every 4 weeks using the EuroQol EQ-5D-5L7 questionnaire. The planned sample size is 28 patients with an expected duration of 25-30 months.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Regorafenib | Experimental | Drug: Regorafenib Oral ProductCycles 1 and 2: * Week 1: 80mg/day * Week 2: 120mg/day * Week 3: 160mg/day * Week 4: off-treatment Cycles 3 on (up to treatment discontinuation) * Weeks 1 to 3: Maximum dose tolerated daily, defined as the highest dose at which the patient had no adverse events grade ≥3 by CTCAE version 5.0 during cycles 1 and 2. * Week 4: off treatment * Dose adjustments may be required. Appendix 11.1 guide dose adjustments. Individual decisions at the occurrence of particular adverse events may be discussed individually within the study team and investigators. Treatment will be administered until any of the following events occur: * Both radiological and clinical progression according to definition of mRECIST or clinical deterioration that prevents treatment continuation according to the judgment of the attending physician * Limiting toxicity as defined by a grade 3 adverse event that does not resolve to grade < 3 within 7 days; adverse event grade 4 or 5. * Subject decision. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- Age 18 years or older;
- Hepatocellular carcinoma with histological or cytological confirmation or that meet radiological criteria for the diagnosis of HCC21;
- BCLC-B stage not candidate for locoregional treatment or BCLC-C;
- Have been previously treated with at least 1 line of systemic treatment with sorafenib, levantinib, atezolizumab plus bevacizumab or other immunotherapy-based regimen;
- Have received the last dose of first-line systemic treatment between 2 and 6 weeks before starting study treatment;
Key exclusion criteria (25 listed)
- Fibrolamellar carcinoma, sarcomatoid HCC or mixed hepatocellular cholangiocarcinoma;
- Previous use of regorafenib;
- Hepatic encephalopathy or medication requirement to control hepatic encephalopathy in the last 60 days before randomization;
- Clinically significant ascites (ie, ascites that requires parcentesis or increased dose of diuretics) within 30 days prior to randomization.
- Patients who have received local therapies (ablation, transarterial chemomebolization or surgery) within 28 days prior to randomization. Radiation treatments with the aim of pain control of bone metastases are allowed.
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 |
|---|---|---|
| Regorafenib Oral ProductDose escalation strategy | Drug | Regorafenib |
Primary outcome
Proportion of patients who complete 4 cycles of treatment
Time frame: 4 months
4 secondary outcomes
Proportion of patients with disease control after 4 treatment cycles;
Time frame: 4 months
Median overall survival: time from treatment initiation to death;
Time frame: 5 years
Median progression-free survival: time from treatment initiation to progression or death
Time frame: 5 years
Score in the The 5-level EuroQol EQ-5D-5L questionnaire
Time frame: 5 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Mar 2026.
- Individual participant dataSharing planned: No
Related trials for Liver Cancer
Not yet recruitingPhase 1
Hepatic Artery Infusion of Carfilzomib in Participants With Liver Metastatic Disease Previously Treated With Hepatic Artery Infusion Pump Therapy
Colorectal Neoplasms, Neoplasms
RecruitingObservational study
Real-world Evaluation of the HistoSonics Edison System for Treatment of Liver Tumors Across Multidisciplinary Users (BOOMBOX: Master Study)
Liver Neoplasms, Primary Liver Cancer
Recruiting
The Vanguard Study: Testing a New Way to Screen for Cancer
Bladder Carcinoma, Breast Carcinoma
Not yet recruitingPhase 2
SAMe in Prevention of Oxaliplatin-associated Liver Injury
Colorectal Cancer, Liver Metastases
Active, not recruitingPhase 1
Prospective Exploratory Study of FAPi PET/CT With Histopathology Validation in Patients With Various Cancers
Bladder Carcinoma, Cervical Carcinoma
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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Regorafenib Oral Product in people with Liver Cancer and Hepatocellular Carcinoma, run by Instituto do Cancer do Estado de São Paulo at 1 site in Brazil.
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 16 inclusion and 25 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: under way, not looking for participants, as of the sponsor's last update on 27 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Brazil. 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?
This study is still under way. Results are not available in the source record yet.
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?
Proportion of patients who complete 4 cycles of treatment (time frame: 4 months). 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 27 Mar 2026.