Dose-escalation of Regorafenib in Advanced Hepatocellular Carcinoma

NCT05622136 | Active Not Recruiting Phase 2

• 1 other identifier: NP3005
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Liver Cancer; Hepatocellular Carcinoma

Keywords

Regorafenib; Hepatocellular carcinoma; Dose; Tolerability; Quality of life

Outcome Measures

Primary Outcomes (1)

• Proportion of patients who complete 4 cycles of treatment

  4 months

Secondary Outcomes (4)

• Proportion of patients with disease control after 4 treatment cycles;

  4 months

• Median overall survival: time from treatment initiation to death;

  5 years

• Median progression-free survival: time from treatment initiation to progression or death

  5 years

• Score in the The 5-level EuroQol EQ-5D-5L questionnaire

  5 years

Study Arms (1)

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.

Drug: Regorafenib Oral Product

Interventions

Regorafenib Oral Product DRUG

Dose escalation strategy

Regorafenib

Eligibility Criteria

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

You may qualify if:

• 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);
• 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:
• i. 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;

You may not qualify if:

• 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.
• 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;

Sponsors & Collaborators

• Instituto do Cancer do Estado de São Paulo: lead

Study Sites (1)

ICESP - Instituto do Câncer do Estado de São Paulo

São Paulo, São Paulo, 01246-000, Brazil

Location

MeSH Terms

Conditions

Liver Neoplasms; Carcinoma, Hepatocellular

Condition Hierarchy (Ancestors)

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator,

Study Record Dates

• First Submitted: November 11, 2022
• First Posted: November 18, 2022
• Study Start: September 10, 2023
• Primary Completion (Estimated): November 15, 2026
• Study Completion (Estimated): December 15, 2026
• Last Updated: March 27, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

BR (1)