Trial Title:
Lenvatinib After Progression on Atezolizumab-bevacizumab in Hepatocellular Carcinoma
NCT ID:
NCT06138769
Condition:
Hepatocellular Carcinoma
Conditions: Official terms:
Carcinoma
Carcinoma, Hepatocellular
Lenvatinib
Conditions: Keywords:
hepatocellular carcinoma
lenvatinib
atezolizumab-bevacizumab
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Active, not recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Lenvatinib
Description:
Lenvatinib 12 mg (body weight 60 kg or greater) or 8 mg (body weight < 60 kg) once orally
every day
Arm group label:
Lenvatinib
Summary:
Although atezolizumab-bevacizumab has been positioned as the standard first-line therapy
in unresectable heptocellular carcinoma, eventually most patients progressed on this
regimen. Despite of multiple drugs are approved for the management of unresectable
hepatocellular carcinoma, only a few trials have been conducted to investigate their
efficacy in the second-line setting after the progression on atezolizumab-bevacizumab.
Lenvatinib is approved first-line multikinase inhibitor in unresectable hepatocellular
carcinoma, but has not yet been investigated as second-line therapy in prospective study.
In this single arm phase 2 study, the efficacy and safety of lenvatinib will be
investigated for patients who progressed on first-line atezolizumab-bevacizumab.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Diagnosis of HCC according to AASLD guidelines
2. Disease that is not amenable to a curative treatment (e.g. surgery, transplant,
radiofrequency ablation)
3. Prior treatment with atezolizumab plus bevacizumab as first-line treatment for
unresectable HCC
4. Progression after atezolizumab plus bevacizumab, the duration of these treatments
must be 2 consecutive treatment cycles or more.
5. At least 1 RECIST v1.1 measurable untreated lesion
6. 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
7. Life expectancy of 12 weeks or longer
8. Age ≥ 19 years old
9. ECOG performance status of 0, 1
10. Adequate hematological function
1. Absolute neutrophil count (ANC) ≥ 1.0 x109/L
2. Platelets ≥ 75 x 109/L
3. Hemoglobin ≥ 10 g/dL
11. Adequate renal function
1. serum creatinine ≤ 1.5 × upper limit of normal or calculated creatinine
clearance ≥ 40 mL/min (using the Cockroft-Gault equation) AND
2. urine protein/creatinine ratio (UPCR) ≤ 1 mg/mg (≤ 113.1 mg/mmol) or 24-hour
urine protein < 1 g
12. Child-Pugh Score of 5 or 6
13. Total bilirubin ≤ 2 mg/dL (≤ 34.2 μmol/L)
14. Serum albumin > 2 g/dL (> 20 g/L)
15. Alanine aminotransferase (ALT) < 3.0 upper limit of normal (ULN)
16. Antiviral therapy per local standard of care if active hepatitis B (HBV) infection
17. Capable of understanding and complying with the protocol requirements and signed
informed consent
18. Sexually active fertile subjects and their partners must agree to use medically
accepted methods of contraception (e.g., 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
19. Females of child-bearing potential must be willing to use effective contraception
during study and for 30 days after the last dose.
Exclusion Criteria:
1. Fibrolamellar carcinoma or mixed hepatocellular cholangiocarcinoma
2. Prior lenvatinib treatment
3. Prior systemic treatment for HCC, except for atezolizumab plus bevacizumab (i.e.
lenvatinib must be second-line systemic treatment)
4. 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.
5. The subject has uncontrolled, significant intercurrent or recent illness including,
but not limited to, the following conditions:
a. Cardiovascular disorders including i. Significant cardiovascular impairment:
history of congestive heart failure greater than New York Heart Association (NYHA)
Class II, unstable angina, myocardial infarction or stroke within 6 months of the
first dose of study drug, or cardiac arrhythmia requiring medical treatment at
Screening.
ii. Uncontrolled blood pressure (Systolic BP>150 mmHg or diastolic BP >90 mmHg) in
spite of an optimized regimen of antihypertensive medication.
iii. Stroke (including TIA), myocardial infarction, or other ischemic event within 6
months iv. Bleeding or thrombotic disorders or subjects at risk for severe
hemorrhage. The degree of tumor invasion/infiltration of major blood vessels (e.g.
carotid artery) should be considered because of the potential risk of severe
hemorrhage associated with tumor shrinkage/necrosis following lenvatinib therapy.
b. Gastrointestinal (GI) disorders including those associated with a high risk of
perforation or fistula formation/bleeding: i. Tumors 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
6. 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
7. Moderate or severe ascites (Radiologically detected but clinically insignificant
ascites is allowed)
8. 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.
9. Subjects having > 1+ proteinuria on urine dipstick testing unless a 24-hour urine
collection for quantitative assessment indicates that the urine protein is <1 g/24
hours.
10. Previously identified allergy or hypersensitivity to components of the study
treatment formulations
11. Females who are breastfeeding or pregnant at Screening or Baseline (as documented by
a positive beta-human chorionic gonadotropin [ß-hCG] (or human chorionic
gonadotropin [hCG]) test with a minimum sensitivity of 25 IU/L or equivalent units
of ß-hCG [or hCG]).
12. Diagnosis of another malignancy within 2 years before randomization, except for
superficial skin cancers, or localized, low-grade tumors deemed cured and not
treated with systemic therapy
13. Electrolyte abnormalities that have not been corrected.
14. Subjects who have not recovered adequately from any toxicity from other anti- cancer
treatment regimens and/or complications from major surgery prior to starting
therapy. Withhold lenvatinib for at least 1 week prior to elective surgery. Do not
administer for at least 2 weeks following major surgery and until adequate wound
healing.
15. The participant has severe hypersensitivity (≥Grade 3) to lenvatinib and/or any of
its excipients.
16. Other clinically significant disorders that are judged by investigators to be
unsuitable for the clinical trial
Gender:
All
Minimum age:
19 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Asan Medical Center
Address:
City:
Seoul
Zip:
05505
Country:
Korea, Republic of
Start date:
July 20, 2023
Completion date:
November 1, 2027
Lead sponsor:
Agency:
Asan Medical Center
Agency class:
Other
Collaborator:
Agency:
Eisai Inc.
Agency class:
Industry
Collaborator:
Agency:
Chonnam National University Hospital
Agency class:
Other
Collaborator:
Agency:
Seoul National University
Agency class:
Other
Collaborator:
Agency:
Gangneung Asan Hospital
Agency class:
Other
Collaborator:
Agency:
Ulsan University Hospital
Agency class:
Other
Collaborator:
Agency:
Chosun University Hospital
Agency class:
Other
Collaborator:
Agency:
Dong-A University Hospital
Agency class:
Other
Collaborator:
Agency:
Bundang CHA Hospital
Agency class:
Other
Collaborator:
Agency:
Seoul National University Bundang Hospital
Agency class:
Other
Collaborator:
Agency:
Yonsei University
Agency class:
Other
Collaborator:
Agency:
Hanyang University Seoul Hospital
Agency class:
Other
Collaborator:
Agency:
Chungnam National University Hospital
Agency class:
Other
Collaborator:
Agency:
Saint Vincent's Hospital, Korea
Agency class:
Other
Collaborator:
Agency:
Gyeongsang National University Hospital
Agency class:
Other
Collaborator:
Agency:
Ewha Womans University
Agency class:
Other
Collaborator:
Agency:
Chungbuk National University Hospital
Agency class:
Other
Collaborator:
Agency:
Severance Hospital
Agency class:
Other
Collaborator:
Agency:
Gachon University Gil Medical Center
Agency class:
Other
Collaborator:
Agency:
The Catholic University of Korea
Agency class:
Other
Collaborator:
Agency:
Bucheon St. Mary's Hospital
Agency class:
Other
Source:
Asan Medical Center
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06138769
