Standard Versus Radiobiologically-Guided Dose Selected SBRT in Liver Cancer

NCT04745390 | Recruiting DMC

• 1 other identifier: SAVIOR
• Study Type: interventional
• Target: 110
• Locations: 1 country
• Sites: 1

Brief Summary

Radiation is a standard treatment option for patients with liver cancer. Unfortunately, the tumour grows after radiation in many patients and radiation can harm normal tissues. A new treatment using a specialized radiation procedure called Stereotactic body radiotherapy (SBRT) may increase the chance to control liver cancer and reduce the chance of harm to normal tissues. SBRT allows radiation treatments to be focused more precisely, and be delivered more accurately than with older treatments. SBRT has become a routine treatment. Further research has found that specialized computer programs can possibly guide the selection of an appropriate SBRT dose. This is called radiobiological guidance. However, this has not yet been proven to improve outcomes and/or reduce toxicity. Therefore, the purpose of this study is to find out if SBRT at standard dose versus SBRT guided by radiobiological techniques is better for you and your liver cancer.

Conditions

Hepatocellular Carcinoma; Liver Metastases

Keywords

Hepatocellular Carcinoma; Radiation Therapy; Stereotactic Body Radiation Therapy

Outcome Measures

Primary Outcomes (2)

• Overall survival

  What will be overall survival of patients in two arms? How many patients progressed in each arm after receiving radiation?

  6 months

• Treated lesion progression

  What is the local radiated lesion progression rate?

  6 months

Secondary Outcomes (6)

• Response rate - Modified RECIST criteria

  6 months

• Extrahepatic failure

  From date of randomization until the date of first documented extrahepatic failure or date of death from any cause, whichever came first, assessed up to 2 years

• Time to intrahepatic progression

  From date of randomization until the date of first documented intrahepatic progression or date of death from any cause, whichever came first, assessed up to 2 years

• Toxicity from the intervention

  6 months

• Comparison of Quality of Life (QOL) Using a Standardly-Used Validated Instrument. Specifically, measures of physical, social/family, and functional well being. Overall symptoms, function, global health status will also be compared.

  Pre-treatment, weekly during treatment, 1 month post treatment, 3 month post treatment, every 3 months up to 5 years.

Study Arms (2)

Standard Dose Radiation

ACTIVE COMPARATOR

Patients in the standard arm will receive a standard dose of 2000cGy in 5 fractions using simple CT planning. IMRT is allowed. Treatment will be every second day excluding weekends and holidays.

Radiation: Radiation therapy

Personalized Dose Selection Radiation

EXPERIMENTAL

Patients in the experimental arm will receive individually selected prescription dose guided by radiobiological parameters described below, preferably delivered in 5 fractions every other day, excluding weekends and holidays. Volumetric-modulated arc therapy (VMAT) is the preferred planning technique. Typical planning uses 2 arcs, \<=10MV and FFF mode where possible as almost all liver treatments are gated). In the event of multiple lesions, multiple isocentres are allowed. Often lateral isocentre shifts are significant and therefore arc ranges should be chosen to minimize collision risk. Treatment will be every second day excluding weekends and holidays.

Radiation: Radiation therapy

Interventions

Radiation therapy RADIATION

Patients will be randomized between standard of care palliative irradiation of 2000cGy in 5 fractions (Arm 1) versus radiobiologically guided dose selection also in 5 fractions (Arm 2). For all patients randomized, radiation is to be delivered in 5 fractions delivered over 5 to 15 days.

Personalized Dose Selection Radiation; Standard Dose Radiation

Eligibility Criteria

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

You may qualify if:

• Eligible patients include patients with any of the following:
• Primary hepatobiliary cancer confirmed pathologically or,
• Non-lymphoma liver metastases confirmed pathologically or,
• Radiographic liver lesions most consistent with metastases, in a patient with known pathologically proven non-lymphoma cancer and a previously negative CT or MRI of the liver or,
• Hepatocellular carcinoma diagnosed with vascular enhancement of the lesion consistent with hepatocellular carcinoma, and with an elevated AFP, in the setting of cirrhosis or chronic hepatitis.
• ≤ 5 liver lesions measurable on a contrast-enhanced liver CT or MRI performed within 90 days prior to study entry.
• Primary liver lesion or liver metastases measuring ≤ 25 cm.
• Extrahepatic cancer is permitted if liver involvement is judged to be life-limiting
• No contraindications to radiotherapy
• Patient must be judged medically or surgically unresectable
• Zubrod Performance Scale = 0-3
• Age \> 18
• Systemic treatment including multikinase inhibitors and immunotherapy are allowed.
• Multikinase inhibitors must be held 2 weeks prior to radiation and may be restarted 1 week post radiation.
• Previous liver resection or ablative therapy is permitted

You may not qualify if:

• Severe cirrhosis or liver failure defined as Child Pugh \>B7
• Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields
• Severe, active co-morbidity, defined as limiting the patient's life to less than 6 months
• Active hepatitis or clinically significant liver failure. Treated hepatitis is permitted.

Sponsors & Collaborators

• London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's: lead

Study Sites (1)

London Regional Cancer Program

London, Ontario, N6A 5W9, Canada

RECRUITING

Related Publications (16)

• Ghouri YA, Mian I, Rowe JH. Review of hepatocellular carcinoma: Epidemiology, etiology, and carcinogenesis. J Carcinog. 2017 May 29;16:1. doi: 10.4103/jcar.JCar_9_16. eCollection 2017.

  PMID: 28694740 BACKGROUND

• De P, Dryer D, Otterstatter MC, Semenciw R. Canadian trends in liver cancer: a brief clinical and epidemiologic overview. Curr Oncol. 2013 Feb;20(1):e40-3. doi: 10.3747/co.20.1190.

  PMID: 23443230 BACKGROUND

• Jarnagin W, Chapman WC, Curley S, D'Angelica M, Rosen C, Dixon E, Nagorney D; American Hepato-Pancreato-Biliary Association; Society of Surgical Oncology; Society for Surgery of the Alimentary Tract. Surgical treatment of hepatocellular carcinoma: expert consensus statement. HPB (Oxford). 2010 Jun;12(5):302-10. doi: 10.1111/j.1477-2574.2010.00182.x.

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• Klein J, Dawson LA. Hepatocellular carcinoma radiation therapy: review of evidence and future opportunities. Int J Radiat Oncol Biol Phys. 2013 Sep 1;87(1):22-32. doi: 10.1016/j.ijrobp.2012.08.043. Epub 2012 Dec 6.

  PMID: 23219567 BACKGROUND

• Mazzaferro V, Regalia E, Doci R, Andreola S, Pulvirenti A, Bozzetti F, Montalto F, Ammatuna M, Morabito A, Gennari L. Liver transplantation for the treatment of small hepatocellular carcinomas in patients with cirrhosis. N Engl J Med. 1996 Mar 14;334(11):693-9. doi: 10.1056/NEJM199603143341104.

  PMID: 8594428 BACKGROUND

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  PMID: 11981766 BACKGROUND

• 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.

  PMID: 16343071 BACKGROUND

• Borgelt BB, Gelber R, Brady LW, Griffin T, Hendrickson FR. The palliation of hepatic metastases: results of the Radiation Therapy Oncology Group pilot study. Int J Radiat Oncol Biol Phys. 1981 May;7(5):587-91. doi: 10.1016/0360-3016(81)90370-9. No abstract available.

  PMID: 6168623 BACKGROUND

• Emami B, Lyman J, Brown A, Coia L, Goitein M, Munzenrider JE, Shank B, Solin LJ, Wesson M. Tolerance of normal tissue to therapeutic irradiation. Int J Radiat Oncol Biol Phys. 1991 May 15;21(1):109-22. doi: 10.1016/0360-3016(91)90171-y.

  PMID: 2032882 BACKGROUND

• Lax I, Blomgren H, Naslund I, Svanstrom R. Stereotactic radiotherapy of malignancies in the abdomen. Methodological aspects. Acta Oncol. 1994;33(6):677-83. doi: 10.3109/02841869409121782.

  PMID: 7946448 BACKGROUND

• McGinn CJ, Ten Haken RK, Ensminger WD, Walker S, Wang S, Lawrence TS. Treatment of intrahepatic cancers with radiation doses based on a normal tissue complication probability model. J Clin Oncol. 1998 Jun;16(6):2246-52. doi: 10.1200/JCO.1998.16.6.2246.

  PMID: 9626227 BACKGROUND

• Dawson LA, McGinn CJ, Normolle D, Ten Haken RK, Walker S, Ensminger W, Lawrence TS. Escalated focal liver radiation and concurrent hepatic artery fluorodeoxyuridine for unresectable intrahepatic malignancies. J Clin Oncol. 2000 Jun;18(11):2210-8. doi: 10.1200/JCO.2000.18.11.2210.

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• 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.

  PMID: 23547075 BACKGROUND

• 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.

  PMID: 20231127 BACKGROUND

• Mendez Romero A, Wunderink W, Hussain SM, De Pooter JA, Heijmen BJ, Nowak PC, Nuyttens JJ, Brandwijk RP, Verhoef C, Ijzermans JN, Levendag PC. Stereotactic body radiation therapy for primary and metastatic liver tumors: A single institution phase i-ii study. Acta Oncol. 2006;45(7):831-7. doi: 10.1080/02841860600897934.

  PMID: 16982547 BACKGROUND

• Tse RV, Hawkins M, Lockwood G, Kim JJ, Cummings B, Knox J, Sherman M, Dawson LA. Phase I study of individualized stereotactic body radiotherapy for hepatocellular carcinoma and intrahepatic cholangiocarcinoma. J Clin Oncol. 2008 Feb 1;26(4):657-64. doi: 10.1200/JCO.2007.14.3529. Epub 2008 Jan 2.

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MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

Radiotherapy

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)

Therapeutics

Study Officials

• Michael Lock, MD

  London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Morgan Black

CONTACT

519-685-8500; morgan.black@lhsc.on.ca

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Radiation Oncologist

Study Record Dates

• First Submitted: January 23, 2021
• First Posted: February 9, 2021
• Study Start: August 1, 2021
• Primary Completion: April 1, 2026
• Study Completion (Estimated): April 1, 2027
• Last Updated: March 11, 2025

Record last verified: 2025-03

Locations

CA (1)