RECRUITING

Tislelizumab Consolidation After Liver-Directed Therapy for Hepatocellular Carcinoma

Conditions

Carcinoma, Hepatocellular Liver Cell Carcinoma Liver-Directed Therapy Tislelizumab Hepatocellular Carcinoma

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

The investigators hypothesize that the addition of Tislelizumab after definitive local therapy for locally advanced inoperable Hepatocellular carcinoma (HCC) will synergize with local therapy as well as treat micro metastatic disease and improve one year progression-free survival rates for participants and optimize local control.

Official Title

Tislelizumab Consolidation After Liver-Directed Therapy for Hepatocellular Carcinoma

Quick Facts

Study Start:2022-07-25

Study Completion:2027-06-01

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT05366829

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
* Each patient eligible to participate in this study must meet all the following criteria: 1. Written informed consent 2. Primary diagnosis of HCC, planned to receive radiation, treatment naïve to systemic therapy for HCC, prior TACE permitted 3. Hepatocellular carcinoma diagnosis by histologic findings and/or imaging criteria of LI-RADS 5 4. Eastern Cooperative Oncology Group performance status score of 0-2 5. Age\>/=18 years 6. Child-Pugh class A liver function or B7, BCLC A-C or deemed not a candidate for surgery or liver transplantation 7. No extrahepatic metastasis detected on CT chest with or without IV contrast, abdomen and pelvis with IV and oral contrast (triphasic-if feasible based on kidney function), or MRI abdomen/liver and chest CT. 8. Females of childbearing potential must be willing to use a highly effective method of birth control for the duration of the study, and ≥ 6 months after the last dose of tislelizumab, and have a negative urine or serum pregnancy test ≤ 7 days of first dose of study drug 9. Non-sterile males must be willing to use a highly effective method of birth control for the duration of the study and for ≥ 6 months after the last dose of tislelizumab. Males must agree not to donate or bank sperm during treatment with tislelizumab and for \> 6 months after treatment stop. 10. Must have 1 target lesion measurable in 1 dimension according to RECIST 1.1. 11. Demonstrate adequate bone marrow and organ function as defined below: 1. Hematologic - Absolute neutrophil count (ANC) ≥ 1,500/mcL, Hemoglobin \> 8.5 g/dL, Platelet count ≥ 75,000/mcL 2. Renal - Serum creatinine OR calculated\* serum creatinine clearance (GFR can be used in place of creatinine or creatinine clearance) ≤ 1.5x upper limit of normal (ULN) OR ≥ 30 mL/min for participants with creatinine levels \> 1.5x institutional ULN * Calculate serum creatinine clearance using the standard Cockcroft-Gault formula. 3. Hepatic - Serum total bilirubin ≤ 3 mg/dL , AST (SGOT) and ALT (SGPT) ≤ 5x ULN , Alkaline phosphatase (ALP) ≤ 8x ULN Coagulation - International Normalized Ratio (INR) or prothrombin time (PT) or activated partial thromboplastin time (aPTT) ≤ 2.0x ULN \*This applies only to participants not receiving therapeutic anticoagulation; participants receiving therapeutic anticoagulation should be on a stable dose.	1. Prior radiotherapy to the region of the liver that would result in excessive doses to normal tissues due to overlap of radiation therapy fields 2. Prior selective internal radiotherapy/hepatic arterial Yttrium therapy, at any time 3. Severe, active co-morbidity as per investigator 4. More than five discrete intrahepatic parenchymal foci of definite HCC or left/right or main portal vein thrombus 5. Direct tumor extension into the stomach, duodenum, small bowel or large bowel 6. Measurable common or main branch biliary duct involvement with HCC 7. Extrahepatic metastases or malignant nodes (that enhance with typical features of HCC) \> 3.0 cm, in sum of maximal diameters (e.g. presence of one 3.4 cm metastatic lymph node or two 2 cm lung lesions). 8. Prior liver transplant 9. HIV positive 10. Immunodeficiency requiring chronic systemic therapy or that may relapse 11. Participants who have received prior immunotherapy. 12. Participants with clinically meaningful ascites, defined as ascites requiring non-pharmacologic intervention (e.g. paracentesis) to maintain symptomatic control 13. Participants with clinically meaningful encephalopathy 14. Participants who have undergone prior solid organ or bone marrow transplant except for patients with prior renal transplant for whom dialysis may be employed in the event of graft rejection. 15. Patients must have documented hepatitis virology status. 16. Participants with a history of autoimmune hypothyroidism on a stable dose of thyroid replacement hormone are eligible. 17. Participants with controlled Type 1 diabetes mellitus on a stable insulin regimen are eligible. 18. Participants with eczema, psoriasis, lichen simplex chronicus of vitiligo with dermatologic manifestations only are eligible provided: 1) rash covers \< 10% of body surface area (BSA), disease is well controlled at baseline and requires only low potency topical steroids (e.g., hydrocortisone 2.5%, hydrocortisone butyrate 0.1%, flucinolone 0.01%, desonide 0.05%, aclometasone dipropionate 0.05%). 19. Any malignancy ≤ 5 years before first dose of study drug except for the specific cancer under investigation in this study and any locally recurring cancer that has been treated curatively (e.g. resected basal or squamous cell skin cancer, superficial bladder cancer, carcinoma in situ of the cervix or breast). 20. Treatment with a live, attenuated vaccine within four weeks prior to initiation of study treatment with Tislelizumab. 1. Note: Seasonal vaccines for influenza and COVID-19 are generally inactivated vaccines and are allowed. Intranasal vaccines are live vaccines and are not allowed. 21. Any condition that required systemic treatment with either corticosteroids (\> 10 mg daily of prednisone or equivalent) or other immunosuppressive medication ≤ 14 days before first dose of study drug a. Note: Participants who are currently or have previously been on any of the following steroid regimens are not excluded: i. Adrenal replacement steroid (dose ≤ 10 mg daily of prednisone or equivalent) ii. Topical, ocular, intra-articular, intranasal, or inhaled corticosteroid with minimal systemic absorption iii. Short course (≤ 7 days) of corticosteroid prescribed prophylactically (e.g., for contrast dye allergy) or for the treatment of a non- autoimmune condition (e.g., delayed-type hypersensitivity reaction caused by contact allergen) 22. With uncontrolled diabetes or \> Grade 1 laboratory test abnormalities in potassium, sodium, or corrected calcium despite standard medical management or ≥ Grade 3 hypoalbuminemia ≤ 14 days before first dose of study drug 23. With history of interstitial lung disease, non-infectious pneumonitis or uncontrolled diseases including pulmonary fibrosis, acute lung diseases, etc. 24. With severe chronic or active infections requiring systemic antibacterial, antifungal or antiviral therapy, including tuberculosis infection, etc. 25. Severe infections within 4 weeks before first dose of study drug, including but not limited to hospitalization for complications of infection, bacteremia, or severe pneumonia. 26. Received therapeutic oral or intravenous antibiotics within two weeks before first dose of study drug 27. Any major surgical procedure requiring general anesthesia ≤ 28 days before first dose of study drug 28. Any of the following cardiovascular risk factors: 29. Has received any herbal medicine used to control cancer within fourteen days of the first study drug administration 30. Participants with toxicities (because of prior anticancer therapy) which have not recovered to baseline or stabilized, except for AEs not considered a likely safety risk (e.g., alopecia, neuropathy and specific laboratory abnormalities) 31. Underlying medical conditions (including laboratory abnormalities) or alcohol or drug abuse or dependence that, will be unfavorable for the administration of study drug or affect the explanation of drug toxicity or AEs or result in insufficient or might impair compliance with study c conduct. 32. Concurrent participation in another therapeutic clinical study.

Inclusion Criteria

Exclusion Criteria

* Each patient eligible to participate in this study must meet all the following criteria:
1. Written informed consent
2. Primary diagnosis of HCC, planned to receive radiation, treatment naïve to systemic therapy for HCC, prior TACE permitted
3. Hepatocellular carcinoma diagnosis by histologic findings and/or imaging criteria of LI-RADS 5
4. Eastern Cooperative Oncology Group performance status score of 0-2
5. Age\>/=18 years
6. Child-Pugh class A liver function or B7, BCLC A-C or deemed not a candidate for surgery or liver transplantation
7. No extrahepatic metastasis detected on CT chest with or without IV contrast, abdomen and pelvis with IV and oral contrast (triphasic-if feasible based on kidney function), or MRI abdomen/liver and chest CT.
8. Females of childbearing potential must be willing to use a highly effective method of birth control for the duration of the study, and ≥ 6 months after the last dose of tislelizumab, and have a negative urine or serum pregnancy test ≤ 7 days of first dose of study drug
9. Non-sterile males must be willing to use a highly effective method of birth control for the duration of the study and for ≥ 6 months after the last dose of tislelizumab. Males must agree not to donate or bank sperm during treatment with tislelizumab and for \> 6 months after treatment stop.
10. Must have 1 target lesion measurable in 1 dimension according to RECIST 1.1.
11. Demonstrate adequate bone marrow and organ function as defined below:
1. Hematologic - Absolute neutrophil count (ANC) ≥ 1,500/mcL, Hemoglobin \> 8.5 g/dL, Platelet count ≥ 75,000/mcL
2. Renal - Serum creatinine OR calculated\* serum creatinine clearance (GFR can be used in place of creatinine or creatinine clearance) ≤ 1.5x upper limit of normal (ULN) OR ≥ 30 mL/min for participants with creatinine levels \> 1.5x institutional ULN
* Calculate serum creatinine clearance using the standard Cockcroft-Gault formula.
3. Hepatic - Serum total bilirubin ≤ 3 mg/dL , AST (SGOT) and ALT (SGPT) ≤ 5x ULN , Alkaline phosphatase (ALP) ≤ 8x ULN Coagulation - International Normalized Ratio (INR) or prothrombin time (PT) or activated partial thromboplastin time (aPTT) ≤ 2.0x ULN \*This applies only to participants not receiving therapeutic anticoagulation; participants receiving therapeutic anticoagulation should be on a stable dose.

1. Prior radiotherapy to the region of the liver that would result in excessive doses to normal tissues due to overlap of radiation therapy fields
2. Prior selective internal radiotherapy/hepatic arterial Yttrium therapy, at any time
3. Severe, active co-morbidity as per investigator
4. More than five discrete intrahepatic parenchymal foci of definite HCC or left/right or main portal vein thrombus
5. Direct tumor extension into the stomach, duodenum, small bowel or large bowel
6. Measurable common or main branch biliary duct involvement with HCC
7. Extrahepatic metastases or malignant nodes (that enhance with typical features of HCC) \> 3.0 cm, in sum of maximal diameters (e.g. presence of one 3.4 cm metastatic lymph node or two 2 cm lung lesions).
8. Prior liver transplant
9. HIV positive
10. Immunodeficiency requiring chronic systemic therapy or that may relapse
11. Participants who have received prior immunotherapy.
12. Participants with clinically meaningful ascites, defined as ascites requiring non-pharmacologic intervention (e.g. paracentesis) to maintain symptomatic control
13. Participants with clinically meaningful encephalopathy
14. Participants who have undergone prior solid organ or bone marrow transplant except for patients with prior renal transplant for whom dialysis may be employed in the event of graft rejection.
15. Patients must have documented hepatitis virology status.
16. Participants with a history of autoimmune hypothyroidism on a stable dose of thyroid replacement hormone are eligible.
17. Participants with controlled Type 1 diabetes mellitus on a stable insulin regimen are eligible.
18. Participants with eczema, psoriasis, lichen simplex chronicus of vitiligo with dermatologic manifestations only are eligible provided: 1) rash covers \< 10% of body surface area (BSA), disease is well controlled at baseline and requires only low potency topical steroids (e.g., hydrocortisone 2.5%, hydrocortisone butyrate 0.1%, flucinolone 0.01%, desonide 0.05%, aclometasone dipropionate 0.05%).
19. Any malignancy ≤ 5 years before first dose of study drug except for the specific cancer under investigation in this study and any locally recurring cancer that has been treated curatively (e.g. resected basal or squamous cell skin cancer, superficial bladder cancer, carcinoma in situ of the cervix or breast).
20. Treatment with a live, attenuated vaccine within four weeks prior to initiation of study treatment with Tislelizumab.
1. Note: Seasonal vaccines for influenza and COVID-19 are generally inactivated vaccines and are allowed. Intranasal vaccines are live vaccines and are not allowed.
21. Any condition that required systemic treatment with either corticosteroids (\> 10 mg daily of prednisone or equivalent) or other immunosuppressive medication ≤ 14 days before first dose of study drug a. Note: Participants who are currently or have previously been on any of the following steroid regimens are not excluded: i. Adrenal replacement steroid (dose ≤ 10 mg daily of prednisone or equivalent) ii. Topical, ocular, intra-articular, intranasal, or inhaled corticosteroid with minimal systemic absorption iii. Short course (≤ 7 days) of corticosteroid prescribed prophylactically (e.g., for contrast dye allergy) or for the treatment of a non- autoimmune condition (e.g., delayed-type hypersensitivity reaction caused by contact allergen)
22. With uncontrolled diabetes or \> Grade 1 laboratory test abnormalities in potassium, sodium, or corrected calcium despite standard medical management or ≥ Grade 3 hypoalbuminemia ≤ 14 days before first dose of study drug
23. With history of interstitial lung disease, non-infectious pneumonitis or uncontrolled diseases including pulmonary fibrosis, acute lung diseases, etc.
24. With severe chronic or active infections requiring systemic antibacterial, antifungal or antiviral therapy, including tuberculosis infection, etc.
25. Severe infections within 4 weeks before first dose of study drug, including but not limited to hospitalization for complications of infection, bacteremia, or severe pneumonia.
26. Received therapeutic oral or intravenous antibiotics within two weeks before first dose of study drug
27. Any major surgical procedure requiring general anesthesia ≤ 28 days before first dose of study drug
28. Any of the following cardiovascular risk factors:
29. Has received any herbal medicine used to control cancer within fourteen days of the first study drug administration
30. Participants with toxicities (because of prior anticancer therapy) which have not recovered to baseline or stabilized, except for AEs not considered a likely safety risk (e.g., alopecia, neuropathy and specific laboratory abnormalities)
31. Underlying medical conditions (including laboratory abnormalities) or alcohol or drug abuse or dependence that, will be unfavorable for the administration of study drug or affect the explanation of drug toxicity or AEs or result in insufficient or might impair compliance with study c conduct.
32. Concurrent participation in another therapeutic clinical study.

Contacts and Locations

Study Contact

Salma Jabbour, MD

CONTACT

732-253-3961

jabbousk@cinj.rutgers.edu

Patrick Boland, MD

CONTACT

732-235-6628

pb564@cinj.rutgers.edu

Principal Investigator

Salma Jabbour, MD

PRINCIPAL_INVESTIGATOR

Rutgers Cancer Institute of New Jersey

Study Locations (Sites)

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, 08903

United States

Montefiore Medical Center

Bronx, New York, 10451

United States

Collaborators and Investigators

Sponsor: Rutgers, The State University of New Jersey

Salma Jabbour, MD, PRINCIPAL_INVESTIGATOR, Rutgers Cancer Institute of New Jersey

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2022-07-25

Study Completion Date2027-06-01

Study Record Updates

Study Start Date2022-07-25

Study Completion Date2027-06-01

Terms related to this study

Keywords Provided by Researchers

Liver-Directed Therapy
Tislelizumab
Hepatocellular Carcinoma

Additional Relevant MeSH Terms

Carcinoma, Hepatocellular
Liver Cell Carcinoma