Sequential TACE and SBRT Followed by ImmunoTherapy for Downstaging HCC for Hepatectomy

NCT03817736 | Completed Phase 2

• 1 other identifier: UW 18-541
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 1

Brief Summary

This study is a prospective phase II, single arm clinical study conducted in Queen Mary Hospital (Hong Kong) assessing the efficacy and safety of the sequential administration of trans-arterial chemo-embolization (TACE) and stereotactic body radiotherapy (SBRT) with an immune checkpoint inhibitor in hepatocellular carcinoma (HCC) patients.

Conditions

HCC

Keywords

HCC; START-FIT; TACE; SBRT; immunotherapy; hepatectomy; hepatocellular carcinoma; liver cancer

Outcome Measures

Primary Outcomes (1)

• Number of Patients Amendable to Curative Surgical Interventions

  Number of patients amendable to curative surgical interventions defined as number of patients receiving curative surgical resection or transplantation after successful down-sizing of tumor(s) by intervention.

  from the date of first study treatment to the date of last study treatment, an average of 3 years

Secondary Outcomes (12)

• Response rate measured by mRECIST criteria

  from the date of screening to radiographically documented progression according to mRECIST 1.1, assessed up to 3 years

• Time to progression (TTP)

  from the date of first study treatment to radiographically documented progression according to mRECIST 1.1, assessed up to 3 years

• Progression-free survival (PFS)

  from the date of first study treatment to radiographically documented progression according to mRECIST 1.1 or death from any cause, whichever occurs first, assessed up to 3 years

• Overall survival (OS)

  from the date of first study treatment to the date of death from any cause, assessed up to 5 years

• European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC-QLQ-C30) Score

  from the date of screening to radiographically documented progression according to mRECIST 1.1, an average of 3 years

Study Arms (1)

START-FIT

EXPERIMENTAL

Single group assignment combining TACE and SBRT with immune checkpoint inhibitor as treatment in HCC patients. Procedure of TACE will be standardized. SBRT screening and planning will be performed by radiation therapists, medical physicists, and oncologists. An immune checkpoint inhibitor may be administered up to 3 days before or after the scheduled day of administration of each cycle due to administrative reasons.

Procedure: TACE; Radiation: SBRT; Drug: Immune Checkpoint Inhibitor

Interventions

TACE PROCEDURE

Procedure of TACE will be standardized.

START-FIT

SBRT RADIATION

SBRT screening and planning will be performed by radiation therapists, medical physicists, and oncologists.

START-FIT

Immune Checkpoint Inhibitor DRUG

An immune checkpoint inhibitor may be administered up to 3 days before or after the scheduled day of administration of each cycle due to administrative reasons.

START-FIT

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of HCC confirmed pathologically or made according to American Association for the Study of Liver Diseases (AASLD) practice guideline 2010: patients with cirrhosis of any etiology and patients with chronic hepatitis B (HBV) who may not have fully developed cirrhosis, the presence of liver nodule \>1cm and demonstrated in a single contrast-enhanced dynamic imaging \[magnetic resonance imaging (MRI)\] of intense arterial uptake and "washout" in portal venous and delayed phases.
• Male or female subjects with age: 18-75 years old
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1
• Tumor size 5-15cm or number of lesions ≤3 or segmental portal vein involvement
• Child-Pugh liver function class A-B7
• Liver volume minus intrahepatic GTV \>700 cc.
• Minimal distance from GTV to stomach, duodenum, small or large bowel \>1 cm.
• No prior systemic therapy nor immunotherapy
• No prior trans-arterial chemo-embolization (TACE)
• No prior radiotherapy to the liver or selective internal radiation (SIRT)
• Written informed consent obtained for clinical trial participation and providing archival tumor tissue, if available.
• At least one measurable lesion according to RECIST v1.1.
• Adequate organ and marrow function, as defined below:
• Hemoglobin ≥9 g/dL
• Absolute neutrophil count ≥1,500/μL

You may not qualify if:

• Prior invasive malignancy within 2 years except for noninvasive malignancies such as cervical carcinoma in situ, in situ prostate cancer, non-melanomatous carcinoma of the skin, lobular or ductal carcinoma in situ of the breast that has been surgically cured
• Contraindicated of SBRT: Any one hepatocellular carcinoma \>15 cm; Total maximal sum of hepatocellular carcinoma \>20 cm; More than 3 discrete hepatic nodule; Direct tumor extension into the stomach, duodenum, small bowel, large bowel, common or main branch of biliary tree
• Severe, active co-morbidity
• Presence of extra-hepatic metastases (M1)
• Left portal vein, right portal vein, main portal vein or inferior vena cava (IVC) thrombosis or involvement
• Presence of clinically meaningful ascites as ascites requiring non pharmacologic intervention (eg, paracentesis) or escalation in pharmacologic intervention to maintain symptomatic control
• Hepatic encephalopathy
• Active or untreated gastrointestinal varices
• Untreated central nervous system (CNS) metastatic disease, lepto-meningeal disease, or cord compression
• Clinically significant (i.e., active) cardiovascular disease: cerebral vascular accident/stroke ( \<6 months prior to enrollment), myocardial infarction ( \<6 months prior to enrollment), unstable angina, congestive heart failure (\>= New York Heart Association Classification Class II), or serious cardiac arrhythmia requiring medication.
• Prior treatment with any immune checkpoint inhibitors or an antibody targeting immuno-regulatory receptors or mechanisms
• Irritable bowel syndrome or other serious gastrointestinal chronic conditions associated with diarrhea within the past 3 years prior to the start of treatment
• Known history of testing positive for HIV or known acquired immunodeficiency syndrome.
• On chronic systemic steroid or any other forms of immunosuppressive medication within 14 days prior to the treatment. Except:
• intranasal, inhaled, topical steroids, or local steroid injection (e.g., intra-articular injection);

Sponsors & Collaborators

• The University of Hong Kong: lead
• Merck KGaA, Darmstadt, Germany: collaborator

Study Sites (1)

Department of Clinical Oncology

Hong Kong, Hong Kong

Location

Related Publications (18)

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• Shim SJ, Seong J, Han KH, Chon CY, Suh CO, Lee JT. Local radiotherapy as a complement to incomplete transcatheter arterial chemoembolization in locally advanced hepatocellular carcinoma. Liver Int. 2005 Dec;25(6):1189-96. doi: 10.1111/j.1478-3231.2005.01170.x.

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• Llovet JM, Ricci S, Mazzaferro V, Hilgard P, Gane E, Blanc JF, de Oliveira AC, Santoro A, Raoul JL, Forner A, Schwartz M, Porta C, Zeuzem S, Bolondi L, Greten TF, Galle PR, Seitz JF, Borbath I, Haussinger D, Giannaris T, Shan M, Moscovici M, Voliotis D, Bruix J; SHARP Investigators Study Group. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med. 2008 Jul 24;359(4):378-90. doi: 10.1056/NEJMoa0708857.

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• Radiation Therapy Oncology Group RTOG 1112 protocol. Available from: https://www.rtog.org/ClinicalTrials/ProtocolTable/StudyDetails.aspx?study=1112.

  BACKGROUND

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• Postow MA, Callahan MK, Barker CA, Yamada Y, Yuan J, Kitano S, Mu Z, Rasalan T, Adamow M, Ritter E, Sedrak C, Jungbluth AA, Chua R, Yang AS, Roman RA, Rosner S, Benson B, Allison JP, Lesokhin AM, Gnjatic S, Wolchok JD. Immunologic correlates of the abscopal effect in a patient with melanoma. N Engl J Med. 2012 Mar 8;366(10):925-31. doi: 10.1056/NEJMoa1112824.

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• Chiang CL, Chiu KWH, Chan KSK, Lee FAS, Li JCB, Wan CWS, Dai WC, Lam TC, Chen W, Wong NSM, Cheung ALY, Lee VWY, Lau VWH, El Helali A, Man K, Kong FMS, Lo CM, Chan AC. Sequential transarterial chemoembolisation and stereotactic body radiotherapy followed by immunotherapy as conversion therapy for patients with locally advanced, unresectable hepatocellular carcinoma (START-FIT): a single-arm, phase 2 trial. Lancet Gastroenterol Hepatol. 2023 Feb;8(2):169-178. doi: 10.1016/S2468-1253(22)00339-9. Epub 2022 Dec 15.

  PMID: 36529152 DERIVED

MeSH Terms

Conditions

Carcinoma, Hepatocellular; Liver Neoplasms

Interventions

Immune Checkpoint Inhibitors

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Antineoplastic Agents, Immunological; Antineoplastic Agents; Therapeutic Uses

Study Officials

• Chi Leung Chiang, Chiang

  The University of Hong Kong

  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: Clinical Assistant Professor

Study Record Dates

• First Submitted: December 6, 2018
• First Posted: January 25, 2019
• Study Start: March 1, 2019
• Primary Completion: June 14, 2022
• Study Completion: July 26, 2023
• Last Updated: May 9, 2024

Record last verified: 2024-05

Locations

HK (1)