Tislelizumab Consolidation After Liver-Directed Therapy for Hepatocellular Carcinoma
Study Details
Study Description
Brief Summary
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 2 |
Detailed Description
Primary Objective:
To determine if consolidation therapy with Tislelizumab following local therapy improves one year progression-free survival in patients with locally advanced, unresectable Hepatocellular carcinoma ( HCC). Progression-free survival (PFS) is defined as the time from first administration of Tislelizumab until the criteria for disease progression is met by response evaluation criteria in solid tumors (RECIST)1.1 or death as a result of any cause, whichever occurs first.
Secondary Objectives:
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To determine if consolidation therapy with Tislelizumab after definitive therapy improves time to metastatic disease and overall survival (OS) in subjects with localized, inoperable Hepatocellular carcinoma (HCC).
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To assess objective response rate, disease control rate, duration of response with consolidation therapy with Tislelizumab after local therapy in subjects with localized, inoperable Hepatocellular carcinoma (HCC).
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To assess the safety profile of Tislelizumab after definitive therapy.
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To assess biomarker response as measured by Alpha fetoprotein (AFP), should the patient's tumor produce AFP.
Exploratory objectives:
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To determine the association of the tumor molecular profile from next-generation sequencing (NGS), of the tissue prior to the initiation of therapy with the treatment response.
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To analyze Circulating tumor DNA (ct DNA) as a biomarker of response to therapy and early detection of disease progression.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Tislelizumab in conjunction with radiation therapy Participants will receive local therapy including TACE+ RT or Ablation (tumors with incomplete ablation) + RT or RT alone (for patients not eligible for TACE or Ablation) and will be screened for eligibility prior to enrollment. Once eligibility has been confirmed, Tislelizumab will be started before radiation therapy and will continue after radiation therapy. Participants who do not receive Tislelizumab for a total of two cycles will be replaced and interpreted for only toxicity analysis. |
Drug: Tislelizumab
Tislelizumab (also known as BGB A317) is a humanized, immunoglobulin G4 (IgG4)-variant monoclonal antibody against programmed cell death protein-1 (PD-1) under clinical development for the treatment of several human malignancies. Tislelizumab consolidation therapy after radiation therapy can capitalize on the immunomodulatory effect of radiotherapy and improve tumor responses and patient outcomes.
|
Outcome Measures
Primary Outcome Measures
- Safety as assessed by number of participants experiencing adverse events [48 months]
Number of participants experiencing adverse events grade three or higher, as defined by Common Terminology Criteria for Adverse Events version 5.0 (NCI-CTCAE v5.0). Severity is a measure of intensity (eg, grade of a specific AE, mild [Grade 1], moderate [Grade 2], severe [Grade 3], or life-threatening [Grade 4]), whereas seriousness is classified by the criteria based on the regulatory definitions. Seriousness serves as the guide for defining regulatory reporting obligations from the Investigator Sponsor to applicable regulatory authorities as described in CTCAE version 5.0.
Secondary Outcome Measures
- Response and progression will be evaluated in this trial using the international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) Committee (v1.1). [48 months]
Changes in only the largest diameter (uni dimensional measurement) of the tumor lesions are used in the RECIST criteria. Measurable Disease: Tumor lesions: Must be accurately measured in at least 1 dimension (longest diameter in the plane of measurement is to be recorded) with a minimum size of: 10 mm by CT scan (irrespective of scanner type) and MRI (no less than double the slice thickness and a minimum of 10 mm) 10 mm caliper measurement by clinical exam (when superficial) 20 mm by chest X ray (if clearly defined and surrounded by aerated lung) Malignant lymph nodes: To be considered pathologically enlarged and measurable, a lymph node must be ≥ 15 mm in short axis when assessed by CT scan (CT scan slice thickness recommended to be no greater than 5 mm). At baseline and in follow up, only the short axis will be measured and followed.
Eligibility Criteria
Criteria
Inclusion Criteria:
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Have provided signed informed consent for the trial
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Aged ≥18 years at the time of informed consent
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Histologic proof of malignancy
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Radiologic or histologic evidence of bone metastases or non-bone metastases
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Eastern Cooperative Oncology Group (ECOG) Performance Status of ≥3
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Pain Score ≥ 3
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Life expectancy of six months or more
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Willing and able to comply with all aspects of the protocol
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A female participant is eligible to participate if she is not pregnant and not breastfeeding
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Woman of childbearing potential who agrees to follow contraceptive guidance during the treatment period and for at least 120 days after the last dose of study treatment.
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A male participant must agree to use contraception during the treatment period and for at least 120 days after the last dose of study treatment
Exclusion Criteria:
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Metastasis from a highly radiosensitive tumor (eg, lymphoma, myeloma, germ cell tumor)
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Spinal metastasis
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Active compression of spinal cord/cauda equina
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Previous RT or SBRT to the same site
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3 sites requiring radiation treatment
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Rutgers Cancer Institute of New Jersey | New Brunswick | New Jersey | United States | 08903 |
Sponsors and Collaborators
- Rutgers, The State University of New Jersey
- BioGene Pharmaceutical Ltd.
- Natera, Inc.
Investigators
- Principal Investigator: Salma Jabbour, MD, Rutgers Cancer Institute of New Jersey
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- CINJ072105
- Pro2021001725