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HCCPhase 2START-FITNCT03817736

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

A Phase 2 study testing TACE, SBRT and Immune Checkpoint Inhibitor in people with HCC, run by The University of Hong Kong at 1 site in Hong Kong.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 to 75 years
Conditions the study is for
HCC
What is being tested?
TACE, SBRT and Immune Checkpoint Inhibitor
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
33 participants
Where
1 siteHong Kong
Study dates
1 Mar 2019to 26 Jul 2023
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
Show all 24Show fewer
  • 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.
  • Subjects with confirmed concomitant HBV infection (defined as HBsAg positive or HBV DNA detectable) that are eligible for inclusion must be treated with antiviral therapy (per local institutional practice) prior to enrollment to ensure adequate viral suppression (HBV DNA <2000 IU/mL), must remain on antiviral therapy for the study duration, and continue therapy for 6 months after the last dose of investigational product(s)
  • 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
  • Platelet count ≥100,000/μL
  • Total bilirubin ≤2.0 × ULN
  • ALT ≤3 × ULN
  • Albumin ≥2.8 g/dL
  • INR ≤1.6
  • Calculated creatinine clearance ≥45 mL/minute as determined by Cockcroft-Gault (using actual body weight) or 24-hour urine creatinine clearance
  • Females of childbearing potential or non-sterilized male who are sexually active must use a highly effective method of contraception
  • Females of childbearing potential must have negative serum or urine pregnancy test

Who cannot join

  • 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
Show all 24Show fewer
  • 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);
  • Systemic corticosteroids at physiologic doses <=10 mg/day of prednisone or equivalent;
  • Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication).
  • Active or prior documented autoimmune or inflammatory disorders in the past 2 years, except diabetes type I, vitiligo, psoriasis, or hypo- or hyperthyroid diseases not requiring immunosuppressive treatment
  • History of primary immunodeficiency or solid organ transplantation
  • Receipt of live, attenuated vaccine within 28 days prior to the study treatment
  • Active infection requiring systemic therapy
  • Severe hypersensitivity reaction to treatment with another monoclonal antibody (mAb)
  • Females who are pregnant, lactating, or intend to become pregnant during their participation in the study
  • Psychiatric disorders and substance (drug/alcohol) abuse

Trial locations and contacts

1 site in 1 country.

Hong Kong1 site

  • Department of Clinical Oncology

    Hong Kong

Other trials in Hong Kong

About this study

Official title: Sequential TransArterial Chemoembolization and Stereotactic RadioTherapy Followed by ImmunoTherapy for Downstaging Hepatocellular Carcinoma for Hepatectomy (START-FIT)

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.

Read the detailed description

All the patients must be registered with the Investigator(s) prior to initiation of treatment. The registration desk will confirm all eligibility criteria and obtain essential information (including patient number).

TACE should start within 28 days of study registration and its procedure will be standardised.

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

Conditions
HCC
Being tested
TACE, SBRT, Immune Checkpoint Inhibitor
Keywords
HCC, START-FIT, TACE, SBRT, immunotherapy, hepatectomy, hepatocellular carcinoma, liver cancer
Medical subject headings
Carcinoma, Hepatocellular, Liver Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • TACEProcedure or surgery

    Procedure of TACE will be standardized.

  • SBRTRadiation

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

  • Immune Checkpoint InhibitorDrug

    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.

Study groups in NCT03817736
Study groupRoleWhat they receive
START-FITExperimentalSingle 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.
Receives: Procedure: TACE; Radiation: SBRT; Drug: Immune Checkpoint Inhibitor

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

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

Secondary outcomes (12)

  1. Response rate measured by mRECIST criteria

    Complete response (CR): Disappearance of any intra-tumoral arterial enhancement in all target lesions Partial response (PR): At least a 30% decrease in the sum of diameters of viable (enhancement in the arterial phase) target lesions, taking as reference the baseline sum of the diameters of target lesions Stable disease (SD): Any cases that do not qualify for either partial response or progressive disease Progressive disease (PD): An increase of at least 20% in the sum of the diameters of viable (enhancing) target lesions, taking as reference the smallest sum of the diameters of viable (enhancing) target lesions recorded since treatment started

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

  2. Time to progression (TTP)

    Time to progression (TTP): measured from the date of first study treatment to radiographically documented progression according to mRECIST 1.1. This does not include death from any cause.

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

  3. Progression-free survival (PFS)

    Progression-free survival (PFS): measured from the date of first study treatment to radiographically documented progression according to mRECIST 1.1 or death from any cause (whichever occurs first). Participants alive and without disease progression or lost to follow-up will be censored at the date of their last radiographic assessment.

    Measured: 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

  4. Overall survival (OS)

    Overall survival (OS): measured from date of first study treatment to the date of death from any cause. Participants alive or lost to follow-up will be censored at the date of their last visit.

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

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

    Quality-of-Life (QoL) is assessed by the European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC-QLQ-C30).

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

  6. Functional Assessment of Cancer Therapy-Hepatobiliary (FACT-Hep) Score

    Quality-of-Life (QoL) is also assessed by the Functional Assessment of Cancer Therapy-Hepatobiliary (FACT-Hep) questionnaires.

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

  7. Incidence of Study-Related Adverse Events [Safety and Tolerability]

    Incidence, nature, and severity of adverse events graded according to the United States National Cancer Institute The Common Terminology Criteria for Adverse Events (NCI CTCAE 4.0)

    Measured: from the date of screening to 90 days after last treatment, around 3 years and 90 days

  8. Pathological response

    Pathological response is assessed as the percentage of surface with non-viable cancer cells (represented by necrosis or fibrosis, the ultimate stage of necrosis) in relation to the total tumor area and will be equal to: 100% - viable cancer cells (%). If there are multiple tumors, the mean percentage will be used. Pathological complete response (pCR) is defined by the absence of viable tumor cells in any nodule.

    Measured: 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 5 years

  9. Disease control rate

    Percentage of patients that had a CR, PR, or SD ≥ 6 months per mRECIST

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

  10. Local control

    Defined as absence of recurrence within the high-dose region (80% isodose volume), demonstrated by new enhancement or mRECIST progressive disease

    Measured: from the date of first study treatment to radiographically documented in-field progression according to mRECIST 1.1, censored at the time of intervention to target lesion, assessed up to 3 years

  11. Duration of response

    Defined as the time from first documented evidence of CR or PR until the first documented sign of disease progression (PD) or death from any cause

    Measured: from the date of first documented evidence of CR or PR to first documented sign of PD or death from any cause according to mRECIST 1.1, assessed up to 3 years

  12. Pattern of failure

    (1) In-field failure: defined as recurrence within the high-dose region (80% iso-dose volume), demonstrated by new enhancement or mRECIST progressive disease; (2) Out-field (intra-hepatic): defined as new or mRECIST progressive disease within liver parenchyma, but outside the SBRT treated volume; (3) New vascular invasion: defined as new portal or hepatic vein invasion; (4) Distant failure: defined as new disease outside liver parenchyma

    Measured: from the date of first study treatment to radiographically documented failure type according to mRECIST 1.1, assessed up to 3 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted25 Jan 2019
  2. Study start1 Mar 2019
  3. Primary completion14 Jun 2022
  4. Study completion26 Jul 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
33 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03817736
Sponsor's protocol ID
UW 18-541
Acronym
START-FIT
Status last verified
May 2024
First submitted
6 Dec 2018
Last updated
9 May 2024
Results posted
No
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • Lo CM, Ngan H, Tso WK, Liu CL, Lam CM, Poon RT, Fan ST, Wong J. Randomized controlled trial of transarterial lipiodol chemoembolization for unresectable hepatocellular carcinoma. Hepatology. 2002 May;35(5):1164-71. doi: 10.1053/jhep.2002.33156.

    PubMed 11981766

  • Llovet JM, Real MI, Montana X, Planas R, Coll S, Aponte J, Ayuso C, Sala M, Muchart J, Sola R, Rodes J, Bruix J; Barcelona Liver Cancer Group. Arterial embolisation or chemoembolisation versus symptomatic treatment in patients with unresectable hepatocellular carcinoma: a randomised controlled trial. Lancet. 2002 May 18;359(9319):1734-9. doi: 10.1016/S0140-6736(02)08649-X.

    PubMed 12049862

  • 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.

    PubMed 16343071

  • 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.

    PubMed 18650514

  • Cheng AL, Kang YK, Chen Z, Tsao CJ, Qin S, Kim JS, Luo R, Feng J, Ye S, Yang TS, Xu J, Sun Y, Liang H, Liu J, Wang J, Tak WY, Pan H, Burock K, Zou J, Voliotis D, Guan Z. Efficacy and safety of sorafenib in patients in the Asia-Pacific region with advanced hepatocellular carcinoma: a phase III randomised, double-blind, placebo-controlled trial. Lancet Oncol. 2009 Jan;10(1):25-34. doi: 10.1016/S1470-2045(08)70285-7. Epub 2008 Dec 16.

    PubMed 19095497

  • Blomgren H, Lax I, Naslund I, Svanstrom R. Stereotactic high dose fraction radiation therapy of extracranial tumors using an accelerator. Clinical experience of the first thirty-one patients. Acta Oncol. 1995;34(6):861-70. doi: 10.3109/02841869509127197.

    PubMed 7576756

  • Cardenes HR, Price TR, Perkins SM, Maluccio M, Kwo P, Breen TE, Henderson MA, Schefter TE, Tudor K, Deluca J, Johnstone PA. Phase I feasibility trial of stereotactic body radiation therapy for primary hepatocellular carcinoma. Clin Transl Oncol. 2010 Mar;12(3):218-25. doi: 10.1007/s12094-010-0492-x.

    PubMed 20231127

  • Andolino DL, Johnson CS, Maluccio M, Kwo P, Tector AJ, Zook J, Johnstone PA, Cardenes HR. Stereotactic body radiotherapy for primary hepatocellular carcinoma. Int J Radiat Oncol Biol Phys. 2011 Nov 15;81(4):e447-53. doi: 10.1016/j.ijrobp.2011.04.011. Epub 2011 Jun 7.

    PubMed 21645977

  • Kang JK, Kim MS, Cho CK, Yang KM, Yoo HJ, Kim JH, Bae SH, Jung DH, Kim KB, Lee DH, Han CJ, Kim J, Park SC, Kim YH. Stereotactic body radiation therapy for inoperable hepatocellular carcinoma as a local salvage treatment after incomplete transarterial chemoembolization. Cancer. 2012 Nov 1;118(21):5424-31. doi: 10.1002/cncr.27533. Epub 2012 May 8.

    PubMed 22570179

  • Bujold A, Massey CA, Kim JJ, Brierley J, Cho C, Wong RK, Dinniwell RE, Kassam Z, Ringash J, Cummings B, Sykes J, Sherman M, Knox JJ, Dawson LA. Sequential phase I and II trials of stereotactic body radiotherapy for locally advanced hepatocellular carcinoma. J Clin Oncol. 2013 May 1;31(13):1631-9. doi: 10.1200/JCO.2012.44.1659. Epub 2013 Apr 1.

    PubMed 23547075

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

  • Huo YR, Eslick GD. Transcatheter Arterial Chemoembolization Plus Radiotherapy Compared With Chemoembolization Alone for Hepatocellular Carcinoma: A Systematic Review and Meta-analysis. JAMA Oncol. 2015 Sep;1(6):756-65. doi: 10.1001/jamaoncol.2015.2189.

    PubMed 26182200

  • Hawkins MA, Dawson LA. Radiation therapy for hepatocellular carcinoma: from palliation to cure. Cancer. 2006 Apr 15;106(8):1653-63. doi: 10.1002/cncr.21811.

    PubMed 16541431

  • Chiang CL, Chan MKH, Yeung CSY, Ho CHM, Lee FAS, Lee VWY, Wong FCS, Blanck O. Combined stereotactic body radiotherapy and trans-arterial chemoembolization as initial treatment in BCLC stage B-C hepatocellular carcinoma. Strahlenther Onkol. 2019 Mar;195(3):254-264. doi: 10.1007/s00066-018-1391-2. Epub 2018 Nov 9.

    PubMed 30413833

  • Gehring AJ, Ho ZZ, Tan AT, Aung MO, Lee KH, Tan KC, Lim SG, Bertoletti A. Profile of tumor antigen-specific CD8 T cells in patients with hepatitis B virus-related hepatocellular carcinoma. Gastroenterology. 2009 Aug;137(2):682-90. doi: 10.1053/j.gastro.2009.04.045. Epub 2009 Apr 23.

    PubMed 19394336

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing TACE, SBRT and Immune Checkpoint Inhibitor in people with HCC, run by The University of Hong Kong at 1 site in Hong Kong.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 24 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 9 May 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Hong Kong. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Patients Amendable to Curative Surgical Interventions (time frame: from the date of first study treatment to the date of last study treatment, an average of 3 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03817736, which also lists 18 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 May 2024.

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