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New treatment option for Locally Advanced Hepatocellular Carcinoma
Official title Atezolizumab in Combination With a Multi-Kinase Inhibitor for the Treatment of Unresectable, Locally Advanced, or Metastatic Liver Cancer
ClinicalTrials.gov ID: NCT05168163
What this study is testing
What is Atezolizumab?
Atezolizumab is an investigational medicine, given as an once-daily infusion into a vein, being studied as a potential treatment for locally advanced hepatocellular carcinoma.
Also referred to as MPDL 3280A, MPDL 328OA.
Plain-language explanation of the investigational treatment - it is being studied and is not an approved or proven therapy. The study team can confirm the details.
- What it's testing
- This phase II trial tests whether atezolizumab in combination with a multi-kinase inhibitor (cabozantinib or lenvatinib) compared to multi-kinase inhibitor alone in treating patients with liver cancer that cannot be removed by surgery (unresectable), has spread to has spread to nearby tissue or lymph nodes (locally advanced), or has spread to other places in the body (metastatic), for which the patient has received treatment in the past (previously treated). 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.
- Phase 2: a mid-size study of how well it works
- Time commitment: about 2 years
- Which group you join is decided by chance.
A plain-language read of the study's public ClinicalTrials.gov listing. The study team confirms the details.
Who can take part
Ages 18 and older
You may be able to join if
- Provide written informed consent =\< 28 days prior to randomization
- Willing to return to enrolling institution for follow-up (during the Active Monitoring Phase of the study)
- NOTE: During the Active Monitoring Phase of a study (i.e., active treatment and clinical follow-up), participants must be willing to return to the...
- Age \>= 18 years
- Hepatocellular carcinoma (HCC) confirmed by histological/cytological diagnosis or clinically per the American Association for the Study of Liver...
You likely can't join if
- Known diagnosis of fibrolamellar carcinoma, sarcomatoid carcinoma or mixed hepatocellular cholangiocarcinoma
- Prior multi-kinase inhibitor treatment for advanced disease (e.g., cabozantinib, lenvatinib, sorafenib, regorafenib)
- NOTE: Use of multi-kinase inhibitor(s) for adjuvant or as part of loco-regional therapies is allowed as long as the therapy was completed \>= 6...
- Any of the following prior therapies:
- Major surgery =\< 4 weeks prior to randomization; Minor surgery =\< 7 days prior to randomization (e.g., simple excision, tooth extraction, insertion...
- Any anti-cancer agent =\< 2 weeks prior to randomization
See the full eligibility criteria
Who can join
- Provide written informed consent =\< 28 days prior to randomization
- Willing to return to enrolling institution for follow-up (during the Active Monitoring Phase of the study)
- NOTE: During the Active Monitoring Phase of a study (i.e., active treatment and clinical follow-up), participants must be willing to return to the consenting institution for follow-up
- Age \>= 18 years
- Hepatocellular carcinoma (HCC) confirmed by histological/cytological diagnosis or clinically per the American Association for the Study of Liver Diseases (AASLD) or WASL 2018 criteria
- Locally advanced, metastatic and/or unresectable disease that is not amendable to curative treatment
- Previously progressed on atezolizumab in combination with bevacizumab as first line systemic therapy for advanced disease
- NOTE: 2nd line patients only
- Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1
- Child Pugh class A
- Documented virology status of hepatitis, as confirmed by screening hepatitis B virus (HBV) and hepatitis C virus (HCV) serology tests.
- For people with active HBV, HBV deoxyribonucleic acid (DNA) \< 500 IU/mL obtained ≤ =\< 28 days prior to randomization, and anti-HBV treatment (per local standard of care; e.g., entecavir) for a minimum of 14 days prior...
- At least one measurable untreated malignant lesion per RECIST v1.1. people who previously received local therapy (e.g., ablation, percutaneous ethanol injection, trans-arterial embolization/chemo-embolization) are...
- Consent to using archival tumor tissues, if available
- NOTE: Non-availability of tumor tissue does not exclude the subject.
- Willingness to provide mandatory blood specimens for correlative research
- Willingness to provide mandatory tissue specimens for correlative research for the first 10 patients per arm (Mayo Clinic Rochester and Mayo Clinic Arizona ONLY)
- Absolute neutrophil count (ANC) \>= 1.5 x 10\^9/L (1500/uL) without granulocyte colony-stimulating factor support (obtained =\< 28 days prior to randomization)
- Lymphocyte count \>= 0.5 x 10\^9/L (500/uL) (obtained =\< 28 days prior to randomization)
- Platelet count \>= 75 x 10\^9/L (75,000/uL) (obtained =\< 28 days prior to randomization)
- Hemoglobin \>= 90 g/L (9 g/dL) (obtained =\< 28 days prior to randomization)
- people may be transfused to meet this criterion
- Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) =\< 5 x upper limit of normal (ULN) (obtained =\< 28 days prior to randomization)
- Total bilirubin =\< 3 x ULN (obtained =\< 28 days prior to randomization)
- Serum albumin \>= 30 g/L (3.0 g/dL) (obtained =\< 28 days prior to randomization)
- For people not receiving therapeutic anticoagulation: international normalized ratio (INR) or partial thromboplastin time (aPTT) =\< 1.5 × ULN (obtained =\< 28 days prior to randomization)
- Serum creatinine =\ = 30 mL/min (calculated using the Cockcroft-Gault formula) (obtained =\< 28 days prior to randomization)
- Negative pregnancy test done =\< 14 days prior to randomization, for women of childbearing potential only
- NOTE: If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
- Resolution of any acute, clinically significant treatment-related toxicity from prior therapy to grade =\< 1 prior to randomization, with the exception of alopecia and peripheral sensory neuropathy.
- people of childbearing potential agree to use two forms of medically approved contraception while taking the study drug and for at least 5 months after the last dose of atezolizumab or multi-kinase inhibitor. people...
- Ability to take oral medications
What rules you out
- Known diagnosis of fibrolamellar carcinoma, sarcomatoid carcinoma or mixed hepatocellular cholangiocarcinoma
- Prior multi-kinase inhibitor treatment for advanced disease (e.g., cabozantinib, lenvatinib, sorafenib, regorafenib)
- NOTE: Use of multi-kinase inhibitor(s) for adjuvant or as part of loco-regional therapies is allowed as long as the therapy was completed \>= 6 months prior to randomization
- Any of the following prior therapies:
- Major surgery =\< 4 weeks prior to randomization; Minor surgery =\< 7 days prior to randomization (e.g., simple excision, tooth extraction, insertion of central lines/Mediport). people with clinically relevant...
- Any anti-cancer agent =\< 2 weeks prior to randomization
- Radiation therapy =\< 4 weeks (1 week for palliative radiation for bone metastases and/or for pain control) or radionuclide treatment (e.g., I-131 or Y-90) =\< 6 weeks prior to randomization
- Treatment with investigational therapy =\< 28 days prior to randomization
- Known brain or leptomeningeal metastasis
- Known co-infection of HBV and HCV. people with a history of HCV infection but who are negative for HCV ribonucleic acid (RNA) by polymerase chain reaction (PCR) will be considered non-infected with HCV
- Active or history of autoimmune disease or immune deficiency, including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel...
- people with a history of autoimmune-related hypothyroidism who are on thyroid-replacement hormone are eligible for the study
- people with controlled Type 1 diabetes mellitus who are on an insulin regimen are eligible for the study
- people with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only (e.g., people with psoriatic arthritis are excluded) are eligible for the study provided all of the following...
- Rash must cover \< 10% of body surface area
- Disease is well controlled at baseline and requires only low-potency topical corticosteroids
- No occurrence of acute exacerbations of the underlying condition requiring psoralen plus ultraviolet A radiation, methotrexate, retinoids, biologic agents, oral calcineurin inhibitors, or high-potency or oral...
- History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed...
- NOTE: History of radiation pneumonitis in the radiation field (fibrosis) is permitted
- Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that contraindicates the use of an investigational drug, may affect the interpretation of the results, or may render...
- Treatment with a live, attenuated vaccine =\< 4 weeks prior to randomization, or anticipation of need for such a vaccine during atezolizumab treatment or =\< 5 months after the last dose of atezolizumab
- History of severe allergic anaphylactic reactions to chimeric or humanized antibodies or fusion proteins
- Known hypersensitivity to Chinese hamster ovary cell products or to any component of the atezolizumab formulation
- people with untreated or incompletely treated esophageal/gastric varices with bleeding or high risk for bleeding. people treated with adequate endoscopic therapy (according to local institutional standards) without any...
- Treatment with systemic immunostimulatory agents (including, but not limited to, interferon and interleukin 2 [IL-2]) =\< 4 weeks or 5 drug elimination half-lives (whichever is longer) prior to randomization
- Prior treatment with CD137 agonists or immune checkpoint blockade therapies, including anti-CTLA-4, anti-PD-1, and anti-PD-L1 therapeutic antibodies
- Note: Prior treatment with atezolizumab is permitted
- Treatment with systemic immunosuppressive medication (including, but not limited to, corticosteroids, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-TNF alpha agents) =\< 2 weeks prior to...
- people who received acute, low-dose systemic immunosuppressant medication or a one-time pulse dose of systemic immunosuppressant medication (e.g., 48 hours of corticosteroids for a contrast allergy) are eligible for the...
- people who received mineralocorticoids (e.g., fludrocortisone), corticosteroids for chronic obstructive pulmonary disease (COPD) or asthma, or low-dose corticosteroids for orthostatic hypotension or adrenal...
- For people who are to receive cabozantinib: Treatment with strong inducers and/or strong inhibitors of CYP3A4 =\< 14 days prior to randomization, including rifampin (and its analogues) or St. John's wort. See...
- Active tuberculosis
- Other uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions:
- Cardiovascular disorders including:
- Symptomatic congestive heart failure, unstable angina, or serious cardiac arrythmias
- Uncontrolled hypertensions defined as sustained blood pressure (BP) \> 150 mmHg systolic BP, or \> 100 mmHg diastolic BP despite optimal antihypertensive treatment
- Stroke (including transient ischemic attack), myocardial infarction, or other ischemic event =\< 3 months prior to randomization.
- Unstable arrythmia
- Thromboembolic event =\< 3 months prior to randomization. people with thromboses of portal/hepatic vasculature attributed to underlying liver disease and/or liver tumor are eligible.
- Active bacterial infection requiring systemic treatment. people on prophylactic antibiotics are eligible.
- Known human immunodeficiency virus (HIV) infection or known acquired immunodeficiency syndrome (AIDS) related illness. people with known HIV but without clinical evidence of an immunocompromised state and receiving...
- Prior allogenic stem cell or solid organ transplantation
- Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently)
- people with indwelling catheters (e.g., PleurX) are allowed.
- Uncontrolled or symptomatic hypercalcemia (ionized calcium \> 1.5 mmol/L, calcium \> 12 mg/dL or corrected serum calcium \> ULN)
- Uncontrolled tumor-related pain
- Patients requiring pain medication must be on a stable regimen at the time of randomization
- Symptomatic lesions (e.g., bone metastases or metastases causing nerve impingement) amenable to palliative radiotherapy should be treated prior to randomization. Patients should be recovered from the effects of...
- Asymptomatic metastatic lesions that would likely cause functional deficits or intractable pain with further growth (e.g., epidural metastasis that is not currently associated with spinal cord compression) should be...
- Other malignancy(ies) =\< 5 years prior to randomization except adequately treated non-melanotic skin cancer, carcinoma-in-situ of the cervix, localized prostate cancer, ductal carcinoma in situ or stage I uterine cancer
- Pregnancy or breastfeeding, or intention of becoming pregnant during study treatment or within at least 5 months after the last dose of study medication
- Uncontrolled hepatic encephalopathy occurring =\< 6 weeks prior to randomization NOTE: Patients with =\< grade 2 encephalopathy =\< 6 weeks prior to randomization are eligible and supportive measures such as lactulose...
The study team makes the final eligibility decision.
Where it's taking place
- Scottsdale, Arizona, United States
- Jacksonville, Florida, United States
- Weston, Florida, United States
- Chicago, Illinois, United States
- Urbana, Illinois, United States
- New Orleans, Louisiana, United States
- Ann Arbor, Michigan, United States
- Rochester, Minnesota, United States
- Buffalo, New York, United States
- Durham, North Carolina, United States
- Cleveland, Ohio, United States
- Pittsburgh, Pennsylvania, United States
- Rapid City, South Dakota, United States
- Milwaukee, Wisconsin, United States
Questions & answers
Do participants get paid in this trial?
This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.
Is it free to join, and do I need insurance?
Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.
How long does this study last?
The study runs about 2 years per participant, based on its public description. The team confirms the exact schedule and number of visits before you enroll.
Who can join this trial?
This study is enrolling all sexes, 18 years and older. The study team makes the final eligibility decision.
Where is this trial taking place?
Study sites include Scottsdale, Arizona, United States; Jacksonville, Florida, United States; Weston, Florida, United States; Chicago, Illinois, United States; Urbana, Illinois, United States; New Orleans, Louisiana, United States and 8 more location(s). Enter your location above to see the nearest site and check your eligibility.
Explore other conditions
BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from ClinicalTrials.gov; the study team decides eligibility.