SBRT and Durvalumab for Inoperable/Unresectable Hepatocellular Carcinoma

NCT04913480 | Unknown Phase 2 DMC

• 1 other identifier: UW 19-655
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 1

Brief Summary

The investigators propose a phase II single-arm study on using stereotactic body radiation therapy in combination with durvalumab for inoperable/unresectable hepatocellular carcinoma. In addition, the investigators will also measure the change in number and intensity of PD-L1-positive circulating tumor cells before and after stereotactic body radiation therapy and durvalumab and evaluate their correlation with treatment response.

Conditions

Hepatocellular Carcinoma

Keywords

Immune checkpoint inhibitor; Stereotactic body radiation therapy

Outcome Measures

Primary Outcomes (1)

• Progression-free survival at 1 year

  Progression-free survival at 1 year

  12 months

Secondary Outcomes (6)

• Best objective response

  36 months

• Local control rate

  36 months

• Liver failure-free rate

  36 months

• Overall survival

  36 months

• Incidence of treatment-related side effects

  36 months

Study Arms (1)

Durvalumab and stereotactic body radiation therapy

EXPERIMENTAL

1. Durvalumab 750mg intravenous infusion once every 2 weeks for 26 cycles, starting 1 week before commencement of stereotactic body radiation therapy 2. Stereotactic body radiation therapy of 27.5Gy to 50Gy in 5 fractions to the liver tumors delivered over 5 to 14 days

Drug: Durvalumab; Radiation: Stereotactic body radiation therapy

Interventions

Durvalumab DRUG

Durvalumab 750mg intravenous infusion once every 2 weeks for 26 cycles

Also known as: MEDI4736

Durvalumab and stereotactic body radiation therapy

Stereotactic body radiation therapy RADIATION

Stereotactic body radiation therapy of 27.5Gy to 50Gy in 5 fractions to the liver tumors delivered over 5 to 14 days.

Also known as: Stereotactic body radiotherapy

Durvalumab and stereotactic body radiation therapy

Eligibility Criteria

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

You may qualify if:

• Patients must have histologically or radiologically confirmed HCC. For radiological diagnosis of HCC, a contrast-enhanced computed tomography or magnetic resonance imaging is mandatory to demonstrate the early arterial enhancement in arterial phase and contrast washout in the porto-venous phase on the imaging.
• Inoperable or unresectable non-metastatic HCC (in the form of tumor resection or liver transplantation) amenable to stereotactic body radiation therapy given in 5 fractions. Prior locoregional therapy including radiofrequency ablation, transarterial chemoembolisation, radioembolisation is allowed provided that radiologically progressive disease is demonstrated following these locoregional therapies.
• Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol. Written informed consent and any locally required authorisation (e.g. Health Insurance Portability and Accountability Act in the US, European Union \[EU\] Data Privacy Directive in the EU) obtained from the patient/legal representative prior to performing any protocol-related procedures, including screening evaluations.
• Be \>/= 18 years of age on day of signing informed consent.
• Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale.
• A stage C or earlier HCC based on Barcelona Clinic Liver Cancer (BCLC) staging system.
• A Child-Pugh of 7 or less.
• Adequate serum hematological functions defined as:
• Absolute neutrophil count (ANC) ≥1.0 x 10\^9/l
• Platelet ≥50 x 10\^9/l
• Hemoglobin ≥9 g/dL
• Adequate serum biochemistry functions defined as:
• Serum bilirubin ≤1.5 x institutional upper limit of normal (ULN). \<\<This will not apply to patients with confirmed Gilbert's syndrome (persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of hemolysis or hepatic pathology), who will be allowed only in consultation with their physician.\>\>
• Serum aspartate aminotransferase (AST) / alanine aminotransferase (ALT) ≤2.5 times of institutional upper limit of normal unless liver metastases are present, in which case it must be ≤5 times of ULN
• Measured creatinine clearance (CL) \>40 mL/min or Calculated creatinine CL\>40 mL/min by the Cockcroft-Gault formula (Cockcroft and Gault 1976) or by 24-hour urine collection for determination of creatinine clearance:

You may not qualify if:

• Is currently participating in or has participated in a study of an investigational agent or using an investigational device within 4 weeks of the first dose of treatment or 5 half-lives, whichever is shorter.
• Has a diagnosis of severe active scleroderma, lupus, other rheumatologic or autoimmune disease within the past 3 months before study recruitment. Patients with a documented history of clinically severe autoimmune disease or a syndrome requiring systemic steroids or immunosuppressive agents will not be allowed on this study. Subjects with vitiligo or resolved childhood asthma/atopy are an exception to this rule. Subjects that require intermittent use of bronchodilators or local steroid injections are not excluded from the study. Subjects with hypothyroidism stable on hormone replacement are not excluded from this study.
• Has had a prior monoclonal antibody, immunotherapy or immune checkpoint inhibitors before recruitment into this study .
• Has had prior chemotherapy or targeted small molecule therapy (including sorafenib or other anti-vascular endothelial growth factor inhibitor) within 3 weeks prior to administration of the study drug or who has not recovered (i.e., ≤Grade 1 or at baseline) from adverse events due to a previously administered agent. \*Note: Subjects with permanent ≤ Grade 2 toxicities (e.g. neuropathy) or toxicities corrected through routine medical management (e.g. thyroid replacement for hypothyroidism), are an exception to this criterion and may qualify for the study. \*Note: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy. \*Note: Subjects with ≤ Grade 2 amylase or lipase elevations abnormalities that have no corresponding clinical manifestations (e.g. manifestation of pancreatitis), are an exception to this criterion and may qualify for the study.
• Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, indolent lymphomas, or in situ cervical cancer that has undergone potentially curative therapy
• Has a history of prior solid organ transplants with or without any episodes of graft-versus-host disease.
• Has a history of allogeneic bone marrow transplantation and peripheral stem cell rescue, with or without any episodes of graft-versus-host disease.
• Has clinically significant or symptomatic ascites requiring either diuretic therapy or paracentesis.
• Has known active extra-hepatic metastases. Patients with treated extra-hepatic metastases which are stable and not requiring any systemic treatment for ≥ 4 weeks are eligible.
• Has known carcinomatous meningitis (also known as leptomeningeal carcinomatosis).
• Has an active infection requiring intravenous systemic therapy or hospital admission.
• Has a history or current evidence of any condition, therapy, or laboratory abnormality, including psychiatric or substance abuse disorder, that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
• Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the screening visit through 31 weeks after the last dose of trial treatment.
• Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies). Routine checking for Anti-HIV1 or Anti-HIV2 is not mandatory.
• Untreated hepatitis B infection. Patients with chronic hepatitis B infection (defined as HBsAg positive) are eligible if they have started anti-viral therapy for at least 1 month and is continuing anti-viral treatment throughout the whole duration of this study.

Sponsors & Collaborators

• The University of Hong Kong: lead

Study Sites (1)

Department of Clinical Oncology, Queen Mary Hospital

Hong Kong, Hong Kong

RECRUITING

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

durvalumab; Radiosurgery

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)

Radiotherapy; Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Victor Ho Fun Lee, MD

  The University of Hong Kong

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Victor Ho Fun Lee, MD

CONTACT

852-2255-4352; vhflee@hku.hk

Mike Law, BSc

CONTACT

852-2255-5034; lawhc703@hku.hk

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Masking Details: No masking
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Associate Professor

Model Details: Combination of stereotactic body radiation therapy and immune checkpoint inhibitor for inoperable/unresectable hepatocellular carcinoma

Study Record Dates

• First Submitted: May 22, 2021
• First Posted: June 4, 2021
• Study Start: October 15, 2020
• Primary Completion: December 31, 2023
• Study Completion: December 31, 2024
• Last Updated: June 4, 2021

Record last verified: 2021-05

Data Sharing

• IPD Sharing: Will not share

Locations

HK (1)