Trial Title:
Cadonilimab and Lenvatinib for Conversion Therapy in Unresectable Hepatocellular Carcinoma
NCT ID:
NCT06215651
Condition:
Cadonilimab and Lenvatinib
Conditions: Official terms:
Carcinoma, Hepatocellular
Lenvatinib
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Cadonilimab lenvatinib
Description:
±TACE/HAIC
Arm group label:
Cadonilimab and lenvatinib
Other name:
AK104
Summary:
This study is a single-arm, open-label, exploratory clinical trial designed to assess the
effectiveness and safety of the combination therapy of Cadonilimab and Lenvatinib for
conversion treatment in unresectable hepatocellular carcinoma. Eligible patients, meeting
the inclusion criteria and providing informed consent, will undergo 3-4 cycles of
Cadonilimab and Lenvatinib conversion therapy. A single imaging assessment will be
conducted, and successfully converted patients will proceed to surgical treatment, with
pathological evaluation of intraoperative specimens. Post-surgery, patients will choose
an appropriate adjuvant treatment based on prior treatment benefits, disease baseline,
and personal preferences.
Patients who do not successfully convert and experience disease progression will exit the
study for alternative treatment. Those who do not successfully convert but do not exhibit
disease progression will continue conversion treatment with Cadonilimab and
Lenvatinib±TACE/HAIC, with tumor imaging assessments every 3 cycles. Successfully
converted patients will undergo surgery, followed by the selection of an appropriate
adjuvant treatment based on prior treatment benefits, disease baseline, and personal
preferences.
Patients who do not successfully convert and experience disease progression will exit the
study for alternative treatment. Those who do not successfully convert but do not exhibit
disease progression will continue conversion treatment with Cadonilimab and
Lenvatinib±TACE/HAIC until disease progression or intolerable toxicity occurs, with a
maximum treatment duration of 2 years. Efficacy assessment will use mRECIST and RECIST
v1.1 criteria, and safety evaluation will follow CTCAE 5.0 standards. Adverse events will
be recorded throughout the study, with a period extending to 60 days after treatment
completion for serious adverse events or those related to Enfortumab Vedotin, and in some
cases extended to 90 days post-treatment.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Participants must sign a written informed consent form before enrollment. Age >18
and ≤75 years, both genders are eligible. Patients with histologically or
pathologically confirmed hepatocellular carcinoma (HCC) or meeting the clinical
diagnostic criteria for HCC according to the American Association for the Study of
Liver Diseases (AASLD).
BCLC stage C without distant or lymphatic metastasis, or BCLC stage B ineligible for
curative surgical treatment.
Presence of measurable lesions (according to RECIST 1.1 criteria, CT scan long diameter
≥10 mm for non-lymph node lesions, CT scan short diameter ≥15 mm for lymph node lesions).
No prior systemic anticancer therapy. No prior local treatment for target lesions,
including TAE, TACE, TARE, surgery, ablation, PEI, or radiotherapy.
Child-Pugh score <7. ECOG PS score: 0-1. At least one untreated measurable lesion
according to RECIST v1.1, or a measurable lesion with confirmed progression after local
treatment (e.g., radiofrequency ablation, ethanol or acetic acid injection, cryoablation,
high-intensity focused ultrasound, arterial embolization, arterial chemoembolization,
etc.) per mRECIST criteria.
Expected survival >12 weeks. Non-surgically sterilized or premenopausal female patients
must use a medically approved contraceptive measure during the study treatment period and
within 3 months after the end of the study treatment. Pregnancy tests for non-surgically
sterilized premenopausal female patients must be negative within 7 days before study
entry, and they must not be lactating. Non-surgically sterilized or fertile male patients
must agree to use a medically approved contraceptive measure with their female partners
during the study treatment period and within 3 months after the end of the study
treatment.
Adequate organ function, excluding any blood component and growth factor use within 14
days:
Hematology: ANC ≥1.5×10^9/L, PLT ≥50×10^9/L, HGB ≥90g/L. Liver function: TBIL ≤3×ULN, ALT
and AST ≤5×ULN, serum albumin ≥28 g/L, ALP ≤5×ULN, and must be stable for at least 1 week
after routine liver protection treatment as assessed by the investigator.
Renal function: Cr ≤1.5×ULN or creatinine clearance ≥50 mL/min (using the standard
Cockcroft-Gault formula), and urine protein <2+; for patients with baseline urine protein
≥2+, a 24-hour urine collection and quantitative measurement with <1g of protein is
required.
Coagulation function: INR and APTT ≤1.5×ULN; for subjects receiving anticoagulant
therapy, PT and INR should be within the planned range.
Exclusion Criteria:
- Previously histologically/cytologically confirmed hepatocellular carcinoma with
fibrolamellar components, sarcomatoid hepatocellular carcinoma, cholangiocarcinoma,
etc.
Prior local or systemic anti-tumor therapy. History of hepatic encephalopathy. History of
liver transplantation. Clinically significant pericardial effusion requiring drainage or
clinically symptomatic pleural effusion.
Clinically evident ascites defined as detectable on physical examination or requiring
drainage during screening.
Concurrent HBV and HCV infection (HCV RNA negative patients with a history of HCV
infection are considered uninfected).
Central nervous system metastasis or leptomeningeal metastasis. History of esophageal or
gastric variceal bleeding due to portal hypertension in the first 6 months before the
initial dose. Participants must have undergone esophagogastroduodenoscopy within 6 months
before the first dose; participants with severe (Grade 3) varices are not allowed to
participate in the study.
Patients with any bleeding diathesis signs or history, experiencing any bleeding or
hemorrhagic events ≥CTCAE Grade 3 within the first 4 weeks before the initial dose.
Occurrence of arterial or venous thromboembolic events in the first 6 months before the
initial dose, including myocardial infarction, unstable angina, cerebrovascular accident
or transient ischemic attack, pulmonary embolism, deep vein thrombosis, or any severe
history of thromboembolism. Exclusion criteria do not apply to stable thrombosis after
routine anticoagulation therapy for implanted venous infusion ports or catheter-related
thrombosis.
Uncontrolled hypertension, with systolic blood pressure >150 mmHg or diastolic blood
pressure >90 mmHg after optimal medical treatment, hypertensive crisis, or a history of
hypertensive encephalopathy.
Symptomatic congestive heart failure (New York Heart Association Class II-IV) or
echocardiographic left ventricular ejection fraction (EF) <50%. Symptomatic or poorly
controlled arrhythmias, including atrial fibrillation or flutter with a ventricular rate
>100 beats/min, a history of congenital long QT syndrome, or a corrected QT interval
(QTc) >450 ms (male) or QTc >470 ms (female) on screening (using the Fridericia method).
A history of myocarditis, cardiomyopathy, or malignant arrhythmias.
Severe bleeding tendency or coagulation disorders, or receiving thrombolytic therapy.
Currently using or recently used (within 10 days before the first dose of study
treatment) aspirin (>325 mg/day) or anticoagulants requiring INR monitoring (such as
warfarin).
History of gastrointestinal perforation and/or fistula within the first 6 months before
the initial dose, history of bowel obstruction (including incomplete bowel obstruction
requiring parenteral nutrition), extensive colon resection (partial colon resection or
extensive small bowel resection with chronic diarrhea), Crohn's disease, ulcerative
colitis, or long-term chronic diarrhea.
Received radiation therapy within the first 3 weeks before the initial dose. Patients who
received radiation therapy more than 7 days before the first dose can be enrolled.
Presence of interstitial lung disease or interstitial lung disease requiring steroid
treatment, either past or current.
Active pulmonary tuberculosis (TB), receiving anti-TB treatment, or having received
anti-TB treatment within the past 1 year before the initial dose.
Subjects with any active autoimmune disease or a history of autoimmune disease (including
but not limited to autoimmune hepatitis, interstitial pneumonia, uveitis, enteritis,
hepatitis, vasculitis, nephritis, hyperthyroidism, hypothyroidism, and those who have
undergone thyroid surgery cannot be included). Subjects with resolved childhood asthma
without the need for intervention can be included; subjects with asthma requiring
bronchodilators for medical intervention cannot be included.
Subjects using immunosuppressive agents, either systemic or locally absorbable steroids
for immunosuppressive purposes (dose >10 mg/day prednisone or equivalent), and still
continuing within the last 2 weeks before enrollment.
Subjects with active infection or unexplained fever >38.5°C during screening or within
the first 4 weeks before the initial dose (subjects with fever related to tumor-induced
fever can be included according to the investigator's judgment).
Patients with objective evidence of past or present lung fibrosis, interstitial
pneumonia, pneumoconiosis, radiation pneumonitis, drug-related pneumonia, or severe
impairment of lung function.
Subjects with congenital or acquired immunodeficiency, such as HIV infection. Subjects
who have not received live vaccines within 4 weeks before the study medication or may
receive live vaccines during the study period.
Subjects with a known history of substance abuse, alcohol abuse, or drug abuse. Patients
unable to take oral medication. The investigator deems it necessary to exclude subjects
from this study. For instance, based on the investigator's judgment, if a participant has
other factors that could potentially lead to the premature termination of the study, such
as the presence of other serious illnesses (including mental disorders) requiring
concurrent treatment, severe gastroesophageal varices, significant laboratory
abnormalities, or factors related to family or social circumstances that could impact the
safety of the participant or the collection of data and samples.
Gender:
All
Minimum age:
18 Years
Maximum age:
75 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Hai-Tao Zhao
Address:
City:
Beijing
Zip:
100730
Country:
China
Status:
Recruiting
Contact:
Last name:
Hai-Tao Zhao, M.D.
Phone:
01069156042
Email:
zhaoht@pumch.cn
Start date:
March 11, 2024
Completion date:
January 2027
Lead sponsor:
Agency:
Peking Union Medical College Hospital
Agency class:
Other
Source:
Peking Union Medical College Hospital
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06215651
