Yttrium Y 90 Glass Microspheres, Atezolizumab, and Cabozantinib for the Treatment of Unresectable or Locally Advanced Hepatocellular Carcinoma

NCT05327738 | Withdrawn Phase 2 FDA Drug FDA Device

• 2 other identifiers: STUDY00023365NCI-2022-01840
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

This phase II trial tests whether yttrium Y 90 glass microspheres, atezolizumab, and cabozantinib work to shrink tumors in patients with liver cancer (hepatocellular carcinoma) that cannot be removed by surgery (unresectable) or that has spread to nearby tissue or lymph nodes (locally advanced). Yttrium Y 90 glass microspheres consists of millions of microscopic glass spheres containing yttrium-90, a radioactive substance. Yttrium Y 90 glass microspheres are delivered to the tumor in the liver through a catheter in an artery. Radiation from the Yttrium-90 helps treat the tumor. Immunotherapy with monoclonal antibodies, such as atezolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Cabozantinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. The combination of yttrium Y 90 glass microspheres, atezolizumab, and cabozantinib may kill more tumor cells.

Conditions

BCLC Stage B Hepatocellular Carcinoma; BCLC Stage C Hepatocellular Carcinoma; Locally Advanced Hepatocellular Carcinoma; Recurrent Hepatocellular Carcinoma; Unresectable Hepatocellular Carcinoma

Outcome Measures

Primary Outcomes (1)

• Proportion of progression-free participants

  Using efficacy analysis set, the proportion of participants that are progression free at 6 months will be reported with 95% exact confidence interval.

  From first dose of study intervention up to 6 months from first dose of study intervention

Secondary Outcomes (9)

• Objective response rate (ORR)

  From first dose of study intervention to end of treatment, assessed up to 12 cycles (1 cycle = 21 days)

• Objective response rate (ORR)

  From first dose of study intervention to end of treatment, assessed up to 12 cycles (1 cycle = 21 days)

• Disease control rate (DCR)

  From first dose of study intervention to date of progression, assessed up to 12 months from start of study intervention

• Disease control rate (DCR)

  From first dose of study intervention to date of progression, assessed up to 12 months from start of study intervention

• Time to disease progression (TTP)

  From first dose of study intervention to date of progression, assessed up to 12 months from start of study intervention

Other Outcomes (1)

• Descriptive summary of tumor and tumor immune cell populations

  Baseline (Day 0) up to end of study, assessed up to 5 years

Study Arms (1)

Treatment (atezolizumab, Y-90, cabozantinib)

EXPERIMENTAL

CYCLE 1: Patients receive atezolizumab IV over 60 minutes on day 1. Within 14 days, patients receive Y-90 intra-arterially. CYCLES 2+: Patients receive atezolizumab IV over 60 minutes on day 1 and cabozantinib PO QD on days 1-21. Treatment repeats every 21 days for a total of 12 cycles in the absence of disease progression or unacceptable toxicity. Patients deriving clinical benefit may continue receiving atezolizumab and cabozantinib beyond cycle 12 at the discretion of the PI.

Biological: Atezolizumab; Procedure: Biopsy; Drug: Cabozantinib S-malate; Radiation: Yttrium Y 90 Glass Microspheres

Interventions

Atezolizumab BIOLOGICAL

Given IV

Also known as: MPDL 3280A, MPDL 328OA, MPDL-3280A, MPDL3280A, MPDL328OA, RG7446, RO5541267, Tecentriq

Treatment (atezolizumab, Y-90, cabozantinib)

Biopsy PROCEDURE

Undergo biopsy

Also known as: BIOPSY_TYPE, Bx

Treatment (atezolizumab, Y-90, cabozantinib)

Cabozantinib S-malate DRUG

Given PO

Also known as: BMS-907351, Cabometyx, Cometriq, XL-184, XL184

Treatment (atezolizumab, Y-90, cabozantinib)

Yttrium Y 90 Glass Microspheres RADIATION

Given intra-arterially

Also known as: TheraSphere

Treatment (atezolizumab, Y-90, cabozantinib)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participant must provide written informed consent before any study-specific procedures or interventions are performed
• Participants aged \>= 18 years
• Capable of understanding and complying with the protocol requirements and must have signed the informed consent document
• Patients must have histologically or cytologically confirmed hepatocellular cancer that is not amenable to transplant or resection:
• Barcelona Clinic Liver Cancer Stage B or C
• Cirrhosis grade of Child-Pugh class A
• Fibrolamellar and mixed hepatocellular/cholangiocarcinoma subtypes are not eligible
• Disease must not be amenable to surgical resection, transplantation, or thermal ablation, or recurrent hepatocellular carcinoma (HCC) after a previous definitive therapy (surgery or thermoablative therapy)
• Venous invasion (portal, hepatic, inferior vena cava \[IVC\], biliary) and infiltrative growth pattern are eligible
• Eastern Cooperative Oncology Group (ECOG) 0 - 1
• Recovery to baseline or =\< grade 1 (per Common Terminology Criteria for Adverse Events \[CTCAE\] version \[v\]5.0) from toxicities related to any prior treatments, unless adverse events (AE\[s\]) are clinically non-significant and/or stable on supportive therapy
• Hemoglobin \>= 9 g/dL (\>= 90 g/L) (within 14 days before first dose of study treatment)
• White blood cell count \>= 2500/uL (within 14 days before first dose of study treatment)
• Absolute neutrophil count (ANC) \>= 1.5 x 10\^9/L (1500/uL), without granulocyte colony-stimulating factor (GSF) support (within 14 days before first dose of study treatment)
• Platelet count \>= 60 x 10\^9/L (\>= 60,000/uL), without transfusion (within 14 days before first dose of study treatment)

You may not qualify if:

• Another primary tumor
• Extrahepatic metastases
• Advanced liver disease with a Child-Pugh B or C, or active gastrointestinal bleeding or encephalopathy or refractory ascites
• Prior systemic therapy for HCC
• Prior Y-90 radioembolization. Prior chemoembolization is permitted
• Radiation therapy for bone metastasis within 2 weeks or any other radiation therapy within 4 weeks before first dose of study treatment. Systemic treatment with radionuclides within 6 weeks before first dose of study treatment. Subjects with clinically relevant ongoing complications from prior radiation therapy are not eligible
• Prior treatment with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent, or with an agent directed to another co-inhibitory T-cell receptor (e.g. CTLA-4, OX-40, and CD137). Note: Patients who have received their first dose of atezolizumab as a first-line treatment of their HCC no longer than 21 days from signing consent, may still be eligible
• Prior treatment with cabozantinib
• Receipt of any type of small molecule kinase inhibitor (including investigational kinase inhibitor) within 2 weeks before first dose of study treatment
• Participants cannot be on other forms of anti-cancer therapy at the same time, except as described within this protocol
• Concomitant anticoagulation with coumarin agents (e.g., warfarin), direct thrombin inhibitors (e.g., dabigatran), direct factor Xa inhibitors (e.g., rivaroxaban), or platelet inhibitors (e.g., clopidogrel). Allowed anticoagulants are the following:
• Prophylactic use of low-dose aspirin for cardio-protection (per local applicable guidelines) and low dose low molecular weight heparins (LMWH)
• Therapeutic doses of LMWH in participants with a screening platelet count \> 100,000/uL, without known brain metastases, and who are on a stable dose of the anticoagulant for at least 1 week before first dose of study treatment without clinically significant hemorrhagic complications from the anticoagulation regimen or the tumor
• Participant has uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions:
• Cardiovascular disorders:

Sponsors & Collaborators

• OHSU Knight Cancer Institute: lead
• Oregon Health and Science University: collaborator

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

atezolizumab; Biopsy; cabozantinib

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Intervention Hierarchy (Ancestors)

Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Specimen Handling; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Adel Kardosh, M.D., Ph.D.

  OHSU Knight Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: April 7, 2022
• First Posted: April 14, 2022
• Study Start: December 10, 2022
• Primary Completion (Estimated): December 4, 2027
• Study Completion (Estimated): December 4, 2027
• Last Updated: December 14, 2022

Record last verified: 2022-12