The purpose of this research is to compare progression free survival between two available systemic therapies - immunotherapy and tyrosine kinase inhibitors - after Therasphere® (yttrium-90) treatment in adult patients with advanced hepatocellular carcinoma. The immunotherapy consists of a standard-of-care treatment with Atezolizumab and Bevacizumab. Treatment with tyrosine kinase inhibitors consists of standard-of-care Lenvatinib or Cabozantinib.
3.1.1 Patients must have a diagnosis of hepatocellular carcinoma (HCC) confirmed by American Association for Study of Liver Diseases (AASLD) guidelines with a Childs-Pugh score of A or B7 [Appendix 5] NOTE: If the patient does not have histological confirmation of disease by biopsy, diagnosis of HCC must be documented with approval by a tumor board or other multidisciplinary conference. Please refer to the appropriate source documents.
3.1.2 Patients must have at least 1 lesion that is measurable using RECIST guidelines. NOTE: A previously irradiated lesion can be considered a target lesion if the lesion is well defined, measurable per RECIST, and has clearly progressed.
3.1.3 Patients may be treatment -naïve or have received any number of prior therapies. NOTE: Prior cancer targeted immunotherapy for any other cancer is contraindicated and not permitted.
3.1.4 Adults ≥18 years old of either gender are eligible.
3.2.1 Patients who are concurrently enrolled in another clinical study unless it is an observational (noninterventional) clinical study or the follow-up period of an interventional study.
3.2.2 Patients who are receiving any other investigational agents within 28 days of registration.
3.2.3 Patients who have a history of allergic reactions attributed to compounds of similar chemical or biologic composition to Y-90, PD-1 &PD-L1 antagonists and TKI's. Note: Patients must not have a history of severe allergic reactions (i.e., Grade 4 allergy, anaphylactic reaction from which the subject did not recover within 6 hours of initiation of supportive care) to any unknown allergens or any components of the systemic therapy
3.2.4 Patients must not have had prior treatment any PDL1 or PD-1 antagonists.
Single group
Y90 + Atezolizumab and Bevacizumab
DrugPatients will receive Durvalumumab + Tremelimumab if Bevacizumab is contraindicated. Patients should begin systemic therapy anytime within 90 days after completion of Y-90 treatment. Treatment will continue until disease progression (clinical or radiological) or unacceptable toxicity/death. Patients will be continued on therapy till either progression is noted (clinical and/or radiological) or if patient is not tolerating therapy. However, there is the possibility of treatment beyond progression per PI discretion.
Y90 + TKI
DrugPatients should begin systemic therapy anytime within 90 days after completion of Y-90 treatment. Treatment will continue until disease progression (clinical or radiological) or unacceptable toxicity/death. Patients will be continued on therapy till either progression is noted (clinical and/or radiological) or if patient is not tolerating therapy. However, there is the possibility of treatment beyond progression per PI discretion.
Progression Free Survival (PFS)
To compare PFS by RECIST v1.1 criteria, with Y90 followed by immunotherapy (atezolizumab + bevacizumab, Arm A) or Y90 followed by TKI treatment (lenvatinib or cabozantinib, Arm B). Progression is defined as either radiological progression (with MRI or CT scan) OR clinical progression.
Time to Progression (TTP)
To compare the TTP in patients with advanced HCC who receive Immunotherapy combination compared to TKI following Y90. The TTP will be measured as the time of the last available radiographical or clinical disease assessment documenting lack of disease progression.
Objective Response Rate (ORR)
To compare the ORR as assessed by RECIST v1.1 in patients with advanced HCC who receive immunotherapy combination and those who receive TKI treatment after Y90. This will be assessed based on imaging.
Duration of Response (DOR)
To compare the DOR in patients by RECIST v1.1 criteria and is defined as either radiological progression (with MRI or CT scan) OR clinical progression.
Clinical Benefit Rates (CBR)
To compare the CBR as assessed by RECIST v1.1, CBR is defined as the percentage of patients with best response documented as Complete Response (CR), plus those with Partial Response (PR) plus those with Stable Disease (SD).
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Northwestern University
Lead sponsor
National Cancer Institute (NCI)
Collaborator
