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Standard Versus Radiobiologically-Guided Dose Selected SBRT in Liver Cancer (SAVIOR)

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ClinicalTrials.gov Identifier: NCT04745390
Recruitment Status : Recruiting
First Posted : February 9, 2021
Last Update Posted : September 8, 2021
Sponsor:
Information provided by (Responsible Party):
Michael Lock, Lawson Health Research Institute

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.


Condition or disease Intervention/treatment Phase
Hepatocellular Carcinoma Liver Metastases Radiation: Radiation therapy Not Applicable

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 110 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase III Randomized Trial of Standard Dose Stereotactic Body Radiation Therapy (SBRT) Versus Radiobiologically-Guided Dose Selected SBRT In Primary or Secondary Liver Carcinoma (SAVIOR).
Actual Study Start Date : August 1, 2021
Estimated Primary Completion Date : April 2026
Estimated Study Completion Date : April 2027

Arm Intervention/treatment
Active Comparator: Standard Dose Radiation
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
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.

Experimental: Personalized Dose Selection Radiation
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
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.




Primary Outcome Measures :
  1. Overall survival [ Time Frame: 6 months ]
    What will be overall survival of patients in two arms? How many patients progressed in each arm after receiving radiation?

  2. Treated lesion progression [ Time Frame: 6 months ]
    What is the local radiated lesion progression rate?


Secondary Outcome Measures :
  1. Response rate - Modified RECIST criteria [ Time Frame: 6 months ]

    To calculate the response rate for each patient according to the modified RECIST criteria.

    • Complete Response: Disappearance of all target lesions
    • Partial Response (PR): At least a 30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum LD
    • Progressive Disease: At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions
    • Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started

  2. Extrahepatic failure [ Time Frame: 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 ]
    Number of patients presented with Extrahepatic failure which defined by Any new lesion present outside of the liver organ.

  3. Time to intrahepatic progression [ Time Frame: 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 ]
    To calculate the time in months or years for cancer recurrence after treatment.

  4. Toxicity from the intervention [ Time Frame: 6 months ]
    Evaluate acute and long-term G3 or larger toxicity based on NCI-CTCAE 5.0 score system. Grade 1 to Grade 5. Higher the grade more severe is the toxicity.

  5. 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. [ Time Frame: Pre-treatment, weekly during treatment, 1 month post treatment, 3 month post treatment, every 3 months up to 5 years. ]
    EORTC QLQ-C30(European Organization for Research and Treatment of Cancer Quality of Life Questionnaire) comprises 5 functional, 3 symptom, 6 single symptom and 1 global health status scale. A higher score denotes a better quality of life for the function and global health scales. A lower score on the symptom and single item scales indicates a lower state of the patient. Overall score will be the primary measure. Scale is 0-100 points.

  6. 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. [ Time Frame: Pre-treatment, weekly during treatment, 1 month post treatment, 3 month post treatment, every 3 months up to 5 years. ]
    FACT-Hep(Functional Assessment of Cancer Therapy-Hepatobiliary questionnaire) is a specific to liver patient quality of life instrument assessing the functional quality of life of patients with hepatobiliary cancer. It has 45 Likert-type items with well-being domains of physical, social/family, emotional, functional plus a hepatobiliary cancer subscale. Aggregate overall lower scores denote a better state of the patient (leading some items to be reverse scored). Overall score will be the primary measure. Scale is 0-180 points.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. 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.
  2. ≤ 5 liver lesions measurable on a contrast-enhanced liver CT or MRI performed within 90 days prior to study entry.
  3. Primary liver lesion or liver metastases measuring ≤ 25 cm.
  4. Extrahepatic cancer is permitted if liver involvement is judged to be life-limiting
  5. No contraindications to radiotherapy
  6. Patient must be judged medically or surgically unresectable
  7. Zubrod Performance Scale = 0-3
  8. Age > 18
  9. 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.

  10. Previous liver resection or ablative therapy is permitted
  11. Chemotherapy must be completed at least 2 weeks prior to radiation therapy and not planned to be administered for at least 1 week (for anthracyclines at least 4 weeks) after completion of treatment.
  12. Life expectancy > 6 months.
  13. Women of childbearing potential and male participants must practice adequate contraception.

Exclusion Criteria:

  1. Severe cirrhosis or liver failure defined as Child Pugh >B7
  2. Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields
  3. Severe, active co-morbidity, defined as limiting the patient's life to less than 6 months
  4. Active hepatitis or clinically significant liver failure. Treated hepatitis is permitted.
  5. Pregnancy, nursing women, or women of childbearing potential, and men who are sexually active and not willing/able to use medically acceptable forms of contraception; this exclusion is necessary because the treatment involved in this study may be teratogenic.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04745390


Contacts
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Contact: Robin Sachdeva, PhD 519-685-8500 ext 54005 robin.sachdeva@lhsc.on.ca

Locations
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Canada, Ontario
London Regional Cancer Program Recruiting
London, Ontario, Canada, N6A 5W9
Contact: Robin Sachdeva, PhD    519-685-8500 ext 54005    robin.sachdeva@lhsc.on.ca   
Principal Investigator: Michael Lock, MD         
Sponsors and Collaborators
Lawson Health Research Institute
Investigators
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Principal Investigator: Michael Lock, MD Lawson Health Research Institute
Publications of Results:

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Responsible Party: Michael Lock, Radiation Oncologist, Lawson Health Research Institute
ClinicalTrials.gov Identifier: NCT04745390    
Other Study ID Numbers: SAVIOR
First Posted: February 9, 2021    Key Record Dates
Last Update Posted: September 8, 2021
Last Verified: August 2021

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Michael Lock, Lawson Health Research Institute:
Hepatocellular Carcinoma
Radiation Therapy
Stereotactic Body Radiation Therapy
Additional relevant MeSH terms:
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Carcinoma
Carcinoma, Hepatocellular
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Liver Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases