Immunotherapy with or without targeted high-dose liver radiation (SBRT) for advanced liver cancer

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

This Phase III randomized trial compares standard immunotherapy-based systemic treatment alone versus the same immunotherapy combined with stereotactic body radiation therapy (SBRT) to the liver in patients with hepatocellular carcinoma (HCC) with macrovascular invasion. Standard immunotherapy regimens may include combinations such as atezolizumab plus bevacizumab, durvalumab plus tremelimumab, or ipilimumab plus nivolumab. Primary outcome is overall survival, with secondary endpoints including progression-free survival, objective response rate, vascular recanalization, AFP decline, toxicity, liver decompensation measures, and quality of life; biospecimens will be collected for exploratory correlative studies. Participants are limited to patients meeting HCC diagnostic criteria with macrovascular invasion and a defined number/size of intrahepatic lesions, and extrahepatic disease is permitted per protocol.

Why it matters

Who can join: the full rules

Inclusion Criteria:

* PRIOR TO STEP 1 REGISTRATION:
* Diagnosis of hepatocellular carcinoma (HCC) by at least 1 criterion listed below:

  * Pathologically (histologically or cytologically) proven diagnosis of HCC (strongly recommended)
  * Radiographically proven (American Association for the Study of Liver Diseases \[AASLD\] criteria) diagnosis of HCC by multiphasic MRI and/or CT scan is allowed.
  * For patients with a prior or concurrent malignancy, pathologic confirmation of hepatocellular cancer is required.
* HCC macrovascular invasion, defined as enhancing vascular thrombosis demonstrating arterial enhancement and venous or delayed venous washout on multiphasic MRI and/or CT is required.
* Presence of extrahepatic metastatic disease on CT chest and CT or MRI pelvis, or PET/CT chest/abdomen/pelvis is permitted.
* 5 or fewer discrete intrahepatic parenchymal foci of HCC.
* Total maximal sum of hepatocellular carcinoma tumors, as a single conglomerate, multiple lesions, or infiltrative HCC \< 20 cm in total summed diameter.
* No direct primary tumor extension into the stomach, duodenum, small bowel, or large bowel.
* No known fibrolamellar HCC, sarcomatoid HCC, or biphenotypic HCC.
* Child-Pugh class A or B7 liver function.
* Age ≥ 18.
* Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
* Not pregnant and not nursing

  * Negative urine or serum pregnancy test (in persons of childbearing potential) within 30 days prior to registration. Childbearing potential is defined as any person who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or who is not postmenopausal.
* Absolute neutrophil count (ANC) ≥ 1,500 cells/mm\^3.
* Platelets ≥ 60,000 cells/mm\^3.
* Hemoglobin ≥ 8g/dl (Note: The use of transfusion or other intervention to achieve hemoglobin \[Hgb\] ≥ 8g/dl is acceptable).
* Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 6 x institutional upper limit of normal (ULN).
* Total bilirubin \< 4 x institutional ULN.
* Creatinine clearance (CrCL) ≥ 30 mL/min/1.73 m\^2 by the Cockcroft-Gault formula.
* For treatment of HCC:

  * Prior surgical resection, transarterial chemoembolization (TACE), and ablation are permitted.
  * No prior systemic therapy or transarterial radioembolization (TARE) for HCC.
  * No history of liver transplantation.
* For prior treatment for any malignancy:

  * Prior systemic therapy for a different cancer is allowable, except for prior immunotherapy.
  * No prior radiotherapy to the region of the study cancer that would result in significant overlap of radiation therapy fields that would lead to excessive cumulative toxicity at the discretion of the investigator.
* No medical contraindication to the standard of care immunotherapy.
* For patients to be treated with atezolizumab/bevacizumab:

  * No history of a gastrointestinal (GI) bleed or other clinically significant bleeding event within 6 months prior to study registration.
* Systemic immunostimulatory agents (including, but not limited to, interferons and interleukin-2 \[IL-2\]) are prohibited within 4 weeks or five drug elimination half-lives (whichever is longer) prior to registration and during the study period.
* No history of allergic reaction to the systemic therapy agent(s), compounds of similar chemical or biologic composition to the systemic therapy agent(s) (or any of its excipients).
* PRIOR TO STEP 2 RANDOMIZATION:
* Obtain confirmation of payment coverage (insurance or other) for both possible treatment arms.

Where it's running

• Alta Bates Summit Medical Center-Herrick Campus
  Berkeley, California, United States Recruiting
• Sutter Cancer Centers Radiation Oncology Services-Cameron Park
  Cameron Park, California, United States Recruiting
• Palo Alto Medical Foundation-Fremont
  Fremont, California, United States Recruiting
• UCI Health - Chao Family Comprehensive Cancer Center and Ambulatory Care
  Irvine, California, United States Recruiting
• Palo Alto Medical Foundation-Camino Division
  Mountain View, California, United States Recruiting
• UC Irvine Health/Chao Family Comprehensive Cancer Center
  Orange, California, United States Recruiting

+89 more sites. See ClinicalTrials.gov for the full list.

Study contacts

• Principal investigator: Jennifer Y Wo — NRG Oncology

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How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.