Advanced hepatocellular carcinoma patients: assessing atezolizumab drug combination and other treatment sequences

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What is this study about?

The study focuses on patients with advanced hepatocellular carcinoma, a type of liver cancer that has spread beyond the liver. It evaluates how different treatment sequences work, using oral medicines such as cabozantinib, regorafenib, lenvatinib and sorafenib, as well as intravenous (given through a vein) agents like atezolizumab, bevacizumab, durvalumab and tremelimumab. The oral drugs are known as targeted therapies because they block signals that help cancer cells grow, while the intravenous drugs are forms of immunotherapy that help the body’s immune system recognize and attack the cancer.

The main goal is to determine which order of these medicines provides the longest overall survival, meaning the length of time a person lives after beginning treatment, while also considering factors such as side effects, quality of life, and treatment costs.

Participants will take the oral pills each day and receive the intravenous infusions at regular clinic visits according to a schedule decided by the treating doctors. Throughout the study, they will have routine medical examinations, imaging scans to see how the cancer is responding, and complete questionnaires that ask about daily wellbeing, side effects, and any financial strain. The study follows each person for months or years, recording what happens as they move from one therapy to the next, to understand which sequence works best.

1 baseline assessment

after you join the study, a series of baseline assessments will be performed. these include a review of your medical history, physical examination, laboratory tests, and imaging studies to document the status of your advanced hepatocellular carcinoma.

the information collected at this stage will be used to determine eligibility for the specific treatment sequences offered in the trial.

2 assignment to first‑line treatment arm

based on the baseline results, you will be assigned to one of the first‑line treatment arms. the study compares two combinations of immunotherapy and anti‑vascular endothelial growth factor (anti‑vegf) agents.

if you are placed in the atezolizumab‑bevacizumab arm, you will receive atezolizumab 1200 mg given by intravenous infusion and bevacizumab 15 mg per kilogram of body weight given by intravenous infusion.

if you are placed in the durvalumab‑tremelimumab arm, you will receive durvalumab 1500 mg given by intravenous infusion and tremelimumab 300 mg given by intravenous infusion.

the exact schedule of the infusions will be determined by the study protocol and your treating physician.

3 first‑line treatment administration and monitoring

you will begin the assigned first‑line therapy according to the dosing schedule. the medications are administered in a clinical setting by qualified staff.

regular follow‑up visits will be scheduled to monitor your safety and to evaluate the effect of the treatment. these visits typically include physical examinations, blood tests, and imaging scans.

any side effects or adverse events will be recorded and managed according to the study guidelines.

4 evaluation for disease progression

periodically, the results of imaging and laboratory tests will be reviewed to determine whether the cancer is responding to the first‑line therapy.

if the disease is found to have progressed, you will be eligible to move to a second‑line treatment sequence as defined by the study.

5 assignment to second‑line treatment arm

for patients who progress after first‑line immunotherapy, the study compares several oral targeted agents with sorafenib as second‑line options.

if you are assigned to the lenvatinib arm, you will take lenvatinib 12 mg by mouth each day.

if you are assigned to the cabozantinib arm, you will take cabozantinib 60 mg by mouth each day.

if you are assigned to the regorafenib arm, you will take regorafenib 160 mg by mouth each day.

if you are assigned to the sorafenib comparator (not listed among the products but part of the study design), you will receive the standard dose of sorafenib as directed by your physician.

6 second‑line treatment administration and monitoring

the selected oral medication will be taken daily as prescribed. you will continue to attend scheduled clinic visits for safety assessments, blood work, and imaging to monitor disease status.

dose adjustments or interruptions may occur based on tolerance and side‑effect profile, following the study protocol.

7 study follow‑up and final assessment

the study will continue to follow you until the end of the trial period, until disease progression that precludes further study treatment, or until death.

final assessments will include overall survival status, quality‑of‑life questionnaires, and collection of any remaining safety data.

the information gathered will contribute to understanding the value of different treatment sequences for advanced hepatocellular carcinoma.

Who Can Join the Study?

Have a diagnosis of advanced liver cancer that cannot be removed by surgery (locally advanced, metastatic, or unresectable hepatocellular carcinoma).
Have good liver health classified as Child‑Pugh class A (a scoring system where class A means the liver works well).
Be at least 18 years old.
Be of any gender.
Sign a written consent form before any study procedures are done.
Follow birth‑control rules: women who could become pregnant must use a highly effective contraceptive method and their male partners must use a condom; men must use a condom and ensure their partner uses another effective method unless they are sterile.
Have an ECOG performance status of 0 to 2 (a scale that measures how well you can carry out daily activities; 0 means fully active, 2 means up and about more than half of waking hours).
Have a life expectancy longer than three months (doctors expect you to live more than three months).
Have adequate kidney and liver function, meaning:
- Blood bilirubin (a waste product) is not higher than 1.5 times the normal upper limit.
- Liver enzymes AST and ALT are not more than five times the normal limit.
- Blood creatinine (a kidney waste marker) is not higher than 1.5 times normal, or your kidney filtration rate is at least 40 mL/min/1.73 m².
Have adequate bone marrow function, meaning:
- Hemoglobin (the protein that carries oxygen) is above 9 g/dL.
- Absolute neutrophil count (a type of white blood cell) is above 1.5 × 10⁹/L.
- Platelet count is above 75 × 10⁹/L for the first part of the study or above 50 × 10⁹/L for the second part.
Have adequate blood clotting ability, meaning INR or PT/aPTT values are ≤1.5 times the normal limit unless you are taking blood‑thinning medication and the values are in the therapeutic range.
If you are a woman who could become pregnant and has not had a hysterectomy or stopped having periods for at least a year, you must have a negative urine or blood pregnancy test at screening.
Provide written consent specific to the part of the study you will join (J‑LI1 or J‑LI2) before any procedures.
For the J‑LI2 part of the study only: must have disease that has gotten worse on scans (radiologically confirmed disease progression) after receiving a first‑line immunotherapy‑based treatment for advanced liver cancer.

Who Cannot Join the Study?

A psychiatric illness that makes it impossible to understand the study and sign the consent form (informed consent).
Having another cancer that has not been completely treated or is still receiving treatment.
Taking any other experimental cancer drug or other cancer treatment at the same time.
Having an active infection, except hepatitis C. Hepatitis B is allowed only if it is controlled with antiviral medicines.
Having brain tumors that cause symptoms or pressure on the spinal cord (symptomatic brain metastases or spinal cord compression).
Having cancer that has spread to the membranes covering the brain and spinal cord (leptomeningeal carcinomatosis).
Having serious heart or blood‑vessel problems, such as:
- A heart attack (myocardial infarction) or unstable chest pain (unstable angina) within the last 6 months.
- Moderate or severe heart failure (New York Heart Association grade II or higher, also called congestive heart failure).
- Blood pressure that is not under control (uncontrolled hypertension).
- A dangerous heart rhythm that needs medication (except common types like atrial fibrillation or paroxysmal supraventricular tachycardia).
- Severe disease of the arteries in the limbs (peripheral vascular disease) that limits daily activities.
- A prolonged heart‑electrical interval (QTc ≥ 470 ms calculated with Fredericia’s correction).
Being allergic (hypersensitivity) to any of the study drugs or their inactive ingredients (excipients).
Any other medical problem, lab result, or personal situation that could make participation unsafe or difficult.
Having had radiation treatment to the brain, chest, or more than 30 % of bone marrow within 4 weeks before starting the study (or 2 weeks if it was only palliative radiation).
Having had major surgery within 28 days before the first dose, unless the wound is fully healed.
Being a breastfeeding mother.
Having ongoing bleeding, a bleeding disorder (coagulopathy), or a condition that makes bleeding likely.
Having enlarged veins in the esophagus (esophageal varices) that have not been properly treated.
Prior medical treatment for advanced liver cancer (advanced hepatocellular carcinoma).
Using medicines that suppress the immune system within 14 days before the first dose (small doses of steroids up to 10 mg prednisone‑equivalent are allowed).
Having an active autoimmune disease (where the body attacks itself) in the past 2 years, except for vitiligo, Graves’ disease, or psoriasis that does not need systemic treatment.
Having inflammatory bowel disease such as Crohn’s disease or ulcerative colitis.
Having had an organ transplant from another person (allogeneic organ transplant).
Having a primary immunodeficiency (a condition that weakens the immune system from birth).
Receiving a live‑attenuated vaccine (a weakened‑virus vaccine) within 30 days before the first dose.
Being unable to swallow pills or having a condition that prevents the drug from being absorbed in the gut (malabsorption).

Where you can join this trial?

Verified and Recommended Sites

No sites found in this category

Verified Sites

Site Name	City	Country
IRCCS Humanitas Research Hospital	Rozzano	Italy
Azienda Ospedaliera Universitaria Federico II Di Napoli	Naples	Italy
Azienda Ospedaliero Universitaria Di Sassari	Sassari	Italy
Azienda Ospedaliera Universitaria Universita’ Degli Studi Della Campania Luigi Vanvitelli	Naples	Italy

Other Sites

Site Name	City	Country
Pia Fondazione Di Culto E Religione Card G Panico	Tricase	Italy
Azienda Ospedaliero-Universitaria San Luigi Gonzaga	Orbassano	Italy
Universita’ Campus Bio-medico Di Roma	Rome	Italy
Ospedale P. Pederzoli Casa Di Cura Privata S.p.A.	Peschiera Del Garda	Italy
Azienda Ospedaliero-Universitaria Maggiore Della Carita	Novara	Italy
Azienda Ospedaliera Sant Anna E San Sebastiano Di Caserta	Caserta	Italy
A.O.U. Policlinico G. Martino Di Messina	Messina	Italy
Centro Di Riferimento Oncologico Di Aviano	Aviano	Italy
Azienda Sanitaria Locale Napoli 2 Nord	Frattamaggiore	Italy
AORN San Giuseppe Moscati Avellino	Avellino	Italy
Azienda Sanitaria Locale Napoli 1 Centro	Naples	Italy
Amsnzkr Ootyaaorcio Pmcq Gfrfcvtf Xqrei	Bergamo	Italy

Trial status

Country	Status	Recruitment Start
Italy	Not yet recruiting	15.09.2026

Trial locations

Investigated Drugs:

CABOZANTINIB is an oral medicine that blocks several signals that help cancer cells grow and spread. In this study it is tested as a possible second‑line treatment for liver cancer after the first therapy has stopped working. Participants receive the drug by swallowing a tablet.

REGORAFENIB is another oral drug that stops the growth of blood vessels that feed tumors and also interferes with cancer cell signals. It is being evaluated as a second‑line option for patients whose disease has progressed after initial therapy. The medication is taken as a tablet.

LENVATINIB is taken by mouth and works by blocking proteins that tumors need to grow and form new blood vessels. The trial is looking at whether this drug can improve survival when used after an immunotherapy‑based first line treatment.

ATEZOLIZUMAB is given by intravenous infusion and belongs to a class of medicines called immune checkpoint inhibitors. It helps the body’s immune system recognize and attack liver cancer cells. In the trial it is compared as the starting immunotherapy in combination with an anti‑VEGF drug.

DURVALUMAB is also an intravenously administered immune checkpoint inhibitor. It is tested together with another immune‑stimulating drug (tremelimumab) to see if this combination works as well as the atezolizumab‑based regimen for first‑line treatment.

BEVACIZUMAB is an intravenous medication that blocks a protein (VEGF) that tumors use to create new blood vessels. It is combined with atezolizumab in the study to evaluate whether this pairing provides better outcomes as an initial therapy.

TREMELIMUMAB is given by IV infusion and works by enhancing the activity of the immune system against cancer. In the trial it is paired with durvalumab to test an alternative first‑line immunotherapy strategy.

SORAFENIB is an oral drug that stops the formation of blood vessels that supply the tumor and also blocks cancer cell growth signals. It serves as the standard comparison treatment (control) for patients receiving a second‑line therapy after immunotherapy.

SORAFENIB (standard comparator) is used in the study as the reference drug against which the newer oral agents (lenvatinib, cabozantinib, and regorafenib) are measured for effectiveness in the second‑line setting. It is taken as a tablet.

Investigated Diseases:

Hepatocellular carcinoma

Advanced hepatocellular carcinoma – Advanced hepatocellular carcinoma is a type of liver cancer that has grown beyond the original tumor site. It begins as a small mass of abnormal liver cells that multiply uncontrollably. As it progresses, the tumor can invade nearby blood vessels and spread to other parts of the liver or to distant organs. The disease often leads to increasing size of the tumor and worsening liver function. Patients may experience symptoms such as abdominal swelling, fatigue, or loss of appetite as the cancer advances.

Trial ID:

2026-525898-39-00

Protocol code:

J-LI

Trial Phase:

Therapeutic use (Phase IV)

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Advanced hepatocellular carcinoma patients: assessing atezolizumab drug combination and other treatment sequences

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