Regorafenib After Progression on Atezolizumab Plus Bevacizumab in Advanced HCC

NCT05134532 | Unknown Phase 2

• 1 other identifier: 2021-05-048-007
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 2

Brief Summary

To investigate efficacy and toxicity of regorafenib after treatment with atezolizumab and bevacizumab combination

Conditions

Hepatocellular Carcinoma

Keywords

Hepatocellular carcinoma; Liver Cancer

Outcome Measures

Primary Outcomes (1)

• Progression-free survival (PFS) by RECIST v 1.1

  the time from start of study treatment to first documentation of objective tumor progression, or to death due to any cause

  up to 36 months

Secondary Outcomes (5)

• Overall survival

  up to 36 months

• Time to progression by RECIST v 1.1

  up to 36 months

• Overall response rate by RECIST v 1.1

  up to 36 months

• Disease control rate by RECIST v 1.1

  up to 36 months

• Safety profiles by NCI-CTCAE version 5

  up to 36 months

Study Arms (1)

intervention

EXPERIMENTAL

Potential subjects will be screened to determine if they meet the eligibility criteria. The screening period is 21 days. Subjects who meet all the eligibility criteria will be commenced regorafenib 160mg once daily for the first 3 weeks of each 4-week cycle.

Drug: regorafenib

Interventions

regorafenib DRUG

Regorafenib 160 mg orally every day for 3 weeks of every 4-week cycle (i.e. 3 weeks on, 1 week off) plus best supportive care

intervention

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of HCC according to AASLD guidelines
• Disease that is not amenable to a curative treatment (e.g. surgery, transplant, radiofrequency ablation)
• Prior treatment with atezolizumab plus bevacizumab combination as 1st line treatment for unresectable HCC
• Progression after atezolizumab plus bevacizumab treatment, The duration of atezolizumab plus bevacizumab must be 2 consecutive treatment cycles or more
• 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
• Life expectancy of 12 weeks or longer
• Age ≥ 19 years old
• ECOG performance status of 0, 1
• Adequate hematological function
• Absolute neutrophil count (ANC) ≥ 1.5 x109/L
• Platelets ≥ 75 x 109/L
• Hemoglobin ≥ 10 g/dL
• Adequate renal function
• serum creatinine ≤ 1.5 × upper limit of normal or calculated creatinine clearance ≥ 40 mL/min (using the Cockroft-Gault equation) AND
• urine protein/creatinine ratio (UPCR) ≤ 1 mg/mg (≤ 113.1 mg/mmol) or 24-hour urine protein \< 1 g

You may not qualify if:

• Fibrolamellar carcinoma or mixed hepatocellular cholangiocarcinoma
• Prior regorafenib treatment
• Prior systemic treatment for HCC, except for atezolizumab plus bevacizumab (i.e. regorafenib must be 2nd line systemic 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 randomization.
• 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 other ischemic event within 6 months iv. Thromboembolic event within 3 months. Subjects with thromboses of portal/hepatic vasculature attributed to underlying liver disease and/or liver tumour are eligible b. Gastrointestinal (GI) disorders including those associated with a high risk of perforation or fistula formation/bleeding: i. Tumours 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 ii. Abdominal fistula, GI perforation, bowel obstruction, intra-abdominal abscess within 6 months
• Major surgery within 2 months before randomization. Complete healing from major surgery must have occurred 1 month before randomization. Complete healing from minor surgery (eg, simple excision, tooth extraction) must have occurred at least 7 days before registration. Subjects with clinically relevant co d. Cavitating pulmonary lesion(s) or endobronchial disease
• Lesion invading a major blood vessel (eg, pulmonary artery or aorta)
• Clinically significant bleeding risk including the following within 28 days of registration: 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
• Gastric or esophageal varices that require interventional treatment within 28 days prior to registration. Prophylaxis with pharmacologic therapy (e.g. non-selective beta blocker) is permitted.
• Moderate or severe ascites (Radiologically detected but clinically insignificant ascites is allowed)
• Corrected QT interval calculated by the Fridericia formula (QTcF) \> 500 ms within 21 days of registration
• \* If the QTcF is \> 500 ms in first ECG, a total of 3 ECGs should be performed. If the average of these 3 consecutive results for QTcF is ≤ 500 ms, the subject meets eligibility in this regard.
• Previously identified allergy or hypersensitivity to components of the study treatment formulations

Sponsors & Collaborators

• CHA University: lead
• Bayer: collaborator

Study Sites (2)

CHA Bundang Medical Center

Seongnam-si, Gyeonggi-do, 13520, South Korea

Location

Asan Medical Center

Seoul, South Korea

Location

Related Publications (13)

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MeSH Terms

Conditions

Carcinoma, Hepatocellular; Liver Neoplasms

Interventions

regorafenib

Condition Hierarchy (Ancestors)

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

Study Officials

• Cheon

  CHA Bundang Medical Center

  PRINCIPAL INVESTIGATOR

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: Assistant professor, Department of Medical Oncology, CHA Bundang Medical Center

Study Record Dates

• First Submitted: November 2, 2021
• First Posted: November 26, 2021
• Study Start: December 24, 2021
• Primary Completion: October 30, 2024
• Study Completion: October 30, 2024
• Last Updated: April 26, 2023

Record last verified: 2023-04

Data Sharing

• IPD Sharing: Will not share

Locations

KR (2)