Liver NeoplasmsNCT01528878
Safety, Efficacy, and Dosing of Stereotactic Radiosurgery for Hepato-cellular Carc/Colo-rectal Liver Metastases
A study testing Stereotactic Radiosurgery using the CyberKnife System. in people with Liver Neoplasms and Colonic Neoplasms, run by UNC Lineberger Comprehensive Cancer Center at 2 sites in United States.
Trial summary
The purpose of this study is to determine a tolerable dose of radiation delivered by the CyberKnife system in two groups of patients with hepatocellular carcinoma (HCC). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Liver Neoplasms, Colonic Neoplasms, Metastatic Cancer to Liver
- What is being tested?
- Stereotactic Radiosurgery using the CyberKnife System.
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 2 sitesUnited States
- Study dates
- Apr 2009to 28 Jan 2016
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Hepatocellular carcinoma (as defined by biopsy or alpha-fetoprotein (AFP) greater than 1000ng/dL with appropriate imaging) or liver metastases from colorectal cancer or other tumor (as defined by biopsy or elevated Carcinoembryonic antigen (CEA) or a positive positron emission tomography (PET) scan in conjunction with a mass on CT or MRI in a patient with previously resected cancer). Patients with at least one measurable liver lesion and no more than 3 are eligible if they meet all other eligibility criteria including the dose constraints on the composite plan.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
- Patients are not candidates for definitive surgical resection because of tumor location, hepatic function, or other medical or personal reasons.
- Patients with HCC who are being considered for liver transplant may be entered as a bridge to transplant if it is considered by the transplant team that an ablative therapy would be of value while awaiting transplant.
- If cirrhosis is present, patients will have Child-Pugh score of A or B (see Appendix A in the Master Protocol).
- Patients will have tumors not optimally treated with radio-frequency ablation by interventional radiology, or by GI/transplant surgery. This could be for reasons of size, tumor location, or other reasons.
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- Ability to place fiducial markers in the vicinity of the tumor to allow for radiographic tracking of respiratory motion and tumor localization. Fiducial placement will generally be done by interventional radiology.
- Estimates of hepatic tolerance must meet the criteria as defined in Section III. This eligibility will not be able to made definitively until the patient has agreed to participate. in the study and the appropriate scan analyses and dosimetry have been performed. No more than one decrement in dose from the planned dose level will be allowed for an individual patient because of exceeding the maximal liver doses before the patient is declared ineligible for study.
- Adequate bone marrow and renal function as assessed by the following:
- Absolute neutrophil count (ANC) > 1000/mm3
- Platelet count > 80,000/mm3
- Creatinine < 2.0 mg/dL OR Creatinine clearance > 45 mL/min based on Cockcroft-Gault formula).
- Patients with extra hepatic metastatic disease are eligible if it is the opinion of the treating physician that local therapy to the liver may produce worthwhile clinical benefits
- Patient is able to understand fully the potential risks and benefits of this approach and signs an appropriate informed consent.
- Male and female of >18 years of age. Male or female patients capable of reproduction must agree to use medically acceptable methods of contraception, such as an intrauterine device, diaphragm, with spermicide, condom with spermicide or abstinence. Inclusion of females of childbearing potential requires a negative pregnancy test within 14 days prior to study initiation.
Who cannot join
- Child-Pugh Class C cirrhosis
- Patients with clinically apparent central nervous system (CNS) disease.
- Medical or psychiatric illness that would not allow the patient to tolerate the proposed treatment including inability to lie flat for an extended period of time, severe claustrophobia or other reasons.
- Uncontrolled or significant cardiovascular disease including: myocardial infarction within 6 months, uncontrolled angina within 6 months, Class III-IV New York Heart Association (NYHA) congestive heart failure, grade 3 cardiac valve dysfunction
- Evidence of decompensated liver disease as evidenced by: clinically significant ascites refractory to diuretic therapy) evidence of hepatic encephalopathy, coagulopathy not corrected by conservative measures.
- A history of CTCAE Grade 3 bleeding esophageal or gastric varices within the past 2 months. Prior variceal bleed permitted if patient has undergone banding or sclerotherapy and there has been no evidence of bleeding for 2 months. Patients at risk for varices (based on the following: known history of esophageal or gastric varices; evidence of hepatic cirrhosis and/or portal hypertension including biopsy-proven cirrhosis, hypersplenism, or radiographic findings of varices) will be screened for esophageal varices. If varices are identified that require intervention (banding), patient will not be eligible until varices adequately treated.
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- Prisoners or patients who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or physical (e.g., infectious disease) illness must not be enrolled into this study.
- Uncontrolled intercurrent illness.
- Inability to comply with study and/or follow-up procedures.
- A patient with Child-Pugh Class A will not be eligible for study if the liver dose constraint described in Section 3.2 cannot be met after two decrements in dose per fraction as described above.
- A patient with Child-Pugh Class B will not be eligible for study if the liver dose constraint described in Section 3.2 cannot be met after two decrements in dose per fraction as described above.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
University of North Carolina at Chapel Hill Lineberger Comprehensive Cancer Center
Chapel Hill, North Carolina, 27599
East Carolina Medical School
Greenville, North Carolina, 27858
About this study
Official title: A Dose-finding, Safety and Preliminary Efficacy Study of Stereotactic Radiosurgery for Hepato-cellular Carcinoma and Metastatic Disease to the Liver.
The purpose of this study is to determine a tolerable dose of radiation delivered by the CyberKnife system in two groups of patients with hepatocellular carcinoma (HCC).
Read the detailed description
The CyberKnife system has been cleared by the U.S. Food and Drug Administration (FDA) to treat lesions, tumors and conditions anywhere in the body when radiation treatment is indicated. In order to treat tumors during the respiratory cycle (vs. increasing the margin of treatment around the tumor to compensate for movement or requiring the patient to breath hold during the delivery of each beam), the Synchrony™ option, a system option that enables dynamic radiosurgery during respiration, will be used. The purpose of this study is to determine a tolerable dose of radiation delivered by the CyberKnife in two groups of patients with hepatocellular carcinoma (HCC).Group 1: Patients with HCC and Childs A cirrhosis, and patients with colorectal liver metastases. Group 2: Patients with Childs B cirrhosis. Patients will be irradiated with radiation doses using the CyberKnife system in 3-5 radiation fractions using guidance from fiducials placed by interventional radiology. Treatments will be delivered with standard CyberKnife procedures to account for respiratory motion and set up variations. The fiducial location will be the prime determinant of the delivery site and respiratory motion and fiducial markers will be placed via percutaneous approach by interventional radiology.
- Being tested
- Stereotactic Radiosurgery using the CyberKnife System.
- Keywords
- Liver Cancer, Hepatocellular Carcinoma, HCC, Metastatic Cancer to Liver, Metastatic Colon Cancer, Metastatic Colo-rectal Cancer, mCRC, Liver Function, Child-Pugh
- Medical subject headings
- Liver Neoplasms, Colonic Neoplasms, Carcinoma, Hepatocellular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Stereotactic Radiosurgery using the CyberKnife System.Radiation
Also called Radiotherapy, CyberKnife, Stereotactic Radiosurgery
Radiation: Stereotactic Radiosurgery using the CyberKnife System. The CyberKnife system has been cleared by the U.S. Food and Drug Administration (FDA) to treat lesions, tumors and conditions, anywhere in the body when radiation treatment is indicated. To address movement of target lesion during the respiratory cycle, the Synchrony™ option will be used.
The Synchrony option precisely tracks tumors in or near the target organ as they move, enabling the highly focused beams of radiation to destroy the tumors with minimal injury to adjacent normal tissue. The Synchrony option records the breathing movements of a patient's chest and combines that information with sequential x-ray pictures of tiny markers inserted inside or in the proximity of the tumor to enable precise delivery of radiation during any point in the respiration cycle. The CyberKnife system with the Synchrony option enables reduced normal tissue exposure by using smaller treatment margins and increased accuracy.
| Study group | Role | What they receive |
|---|---|---|
| Good liver function. | Experimental | Patients with good liver function as defined by no more than Child-Pugh Class A. Receives: Radiation: Stereotactic Radiosurgery using the CyberKnife System. |
| Compromised liver function. | Experimental | Patients with compromised liver function as defined by patients with Child-Pugh Class B. Receives: Radiation: Stereotactic Radiosurgery using the CyberKnife System. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Tolerability of Stereotactic Body Radiotherapy (SBRT) Based on Number of Cumulative Acute Toxicities Occurring Within 90 Days of Treatment and Related to SBRT.
To determine a tolerable dose, cumulative acute toxicity was collected (defined as toxicity occurring within 90 days of treatment initiation). Adverse events were graded by the Common Terminology Criteria for Adverse Events version 3.0. Tolerability was based on hepatic toxicity. A grading (severity) scale is provided for each adverse event (AE) term. Grade 1 Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2 Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental Activities of Daily Living (ADL). Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL. Grade 4 Life-threatening consequences; urgent intervention indicated. Grade 5 Death related to AE.
Measured: 90 days
Secondary outcomes (3)
Local Tumor Control to Doses of Radiation in Patients With Liver Cancer or Metastases to the Liver
1 year local control defined as percentage of patients with freedom from local progression at a median follow-up time of 12.7 months. Progressive disease is defined as increase by >= 50% of product of the two perpendicular diameters of an irradiated lesion.
Measured: 12.7 months
Percentage of Local Response to Doses of Radiation in Patients With Liver Cancer or Metastases to the Liver
Complete response (CR) is defined as disappearance of the target lesion, partial response (PR) as regression of measureable disease, progressive disease (PD) as increase by >= 50% in product of the two perpendicular diameters of an irradiated lesion, and stable disease (SD) as all others not meeting criteria for CR, PR, or PD.
Measured: 6 months
Overall Survival of Patients With Liver Cancer or Metastases to the Liver
Overall survival is defined as percentage of patients remaining alive from start of study treatment to 1 year.
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Feb 2012 (estimated)
- Study startApr 2009
- Primary completion18 Aug 2014
- Study completion28 Jan 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Liver NeoplasmsStudies of the same condition, open and under way.
- More trials run by UNC Lineberger Comprehensive Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 N/A
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- UNC Lineberger Comprehensive Cancer Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Joel Tepper, MD, Principal investigator, University of North Carolina at Chapel Hill Lineberger Comprehensive Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01528878
- Sponsor's protocol ID
- LCCC 0809
- Status last verified
- Jun 2018
- First submitted
- 9 Jan 2012
- Last updated
- 26 Jul 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 26 Jul 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Dose-finding, Safety and Preliminary Efficacy Study of Stereotactic Radiosurgery for Hepato-cellular Carcinoma and Metastatic Disease to the Liver.
- ClinicalTrials.gov ID
- NCT01528878
- Acronym / sponsor ID
- LCCC 0809
- Keywords
- Liver Cancer, Hepatocellular Carcinoma, HCC, Metastatic Cancer to Liver, Metastatic Colon Cancer, Metastatic Colo-rectal Cancer, mCRC, Liver Function
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- UNC Lineberger Comprehensive Cancer CenterUniversity, hospital or other
- Study start
- Apr 2009
- Primary completion
- 18 Aug 2014 (actual)
- Study completion
- 28 Jan 2016 (actual)
- First posted
- 8 Feb 2012 (estimated)
- Results
- Posted 15 May 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to determine a tolerable dose of radiation delivered by the CyberKnife system in two groups of patients with hepatocellular carcinoma (HCC).
Detailed description
The CyberKnife system has been cleared by the U.S. Food and Drug Administration (FDA) to treat lesions, tumors and conditions anywhere in the body when radiation treatment is indicated. In order to treat tumors during the respiratory cycle (vs. increasing the margin of treatment around the tumor to compensate for movement or requiring the patient to breath hold during the delivery of each beam), the Synchrony™ option, a system option that enables dynamic radiosurgery during respiration, will be used. The purpose of this study is to determine a tolerable dose of radiation delivered by the CyberKnife in two groups of patients with hepatocellular carcinoma (HCC).Group 1: Patients with HCC and Childs A cirrhosis, and patients with colorectal liver metastases. Group 2: Patients with Childs B cirrhosis. Patients will be irradiated with radiation doses using the CyberKnife system in 3-5 radiation fractions using guidance from fiducials placed by interventional radiology. Treatments will be delivered with standard CyberKnife procedures to account for respiratory motion and set up variations. The fiducial location will be the prime determinant of the delivery site and respiratory motion and fiducial markers will be placed via percutaneous approach by interventional radiology.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Good liver function. | Experimental | Radiation: Stereotactic Radiosurgery using the CyberKnife System.Patients with good liver function as defined by no more than Child-Pugh Class A. |
| Compromised liver function. | Experimental | Radiation: Stereotactic Radiosurgery using the CyberKnife System.Patients with compromised liver function as defined by patients with Child-Pugh Class B. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Hepatocellular carcinoma (as defined by biopsy or alpha-fetoprotein (AFP) greater than 1000ng/dL with appropriate imaging) or liver metastases from colorectal cancer or other tumor (as defined by biopsy or elevated Carcinoembryonic antigen (CEA) or a positive positron emission tomography (PET) scan in conjunction with a mass on CT or MRI in a patient with previously resected cancer). Patients with at least one measurable liver lesion and no more than 3 are eligible if they meet all other eligibility criteria including the dose constraints on the composite plan.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
- Patients are not candidates for definitive surgical resection because of tumor location, hepatic function, or other medical or personal reasons.
- Patients with HCC who are being considered for liver transplant may be entered as a bridge to transplant if it is considered by the transplant team that an ablative therapy would be of value while awaiting transplant.
- If cirrhosis is present, patients will have Child-Pugh score of A or B (see Appendix A in the Master Protocol).
Key exclusion criteria (11 listed)
- Child-Pugh Class C cirrhosis
- Patients with clinically apparent central nervous system (CNS) disease.
- Medical or psychiatric illness that would not allow the patient to tolerate the proposed treatment including inability to lie flat for an extended period of time, severe claustrophobia or other reasons.
- Uncontrolled or significant cardiovascular disease including: myocardial infarction within 6 months, uncontrolled angina within 6 months, Class III-IV New York Heart Association (NYHA) congestive heart failure, grade 3 cardiac valve dysfunction
- Evidence of decompensated liver disease as evidenced by: clinically significant ascites refractory to diuretic therapy) evidence of hepatic encephalopathy, coagulopathy not corrected by conservative measures.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Stereotactic Radiosurgery using the CyberKnife System.Also: Radiotherapy, CyberKnife, Stereotactic RadiosurgeryRadiation: Stereotactic Radiosurgery using the CyberKnife System. The CyberKnife system has been cleared by the U.S. Food and Drug Administration (FDA) to treat lesions, tumors and conditions, anywhere in the body when radiation treatment is indicated. To address movement of target lesion during the respiratory cycle, the Synchrony™ option will be used. The Synchrony option precisely tracks tumors in or near the target organ as they move, enabling the highly focused beams of radiation to destroy the tumors with minimal injury to adjacent normal tissue. The Synchrony option records the breathing movements of a patient's chest and combines that information with sequential x-ray pictures of tiny markers inserted inside or in the proximity of the tumor to enable precise delivery of radiation during any point in the respiration cycle. The CyberKnife system with the Synchrony option enables reduced normal tissue exposure by using smaller treatment margins and increased accuracy. | Radiation | Compromised liver function., Good liver function. |
Primary outcome
Tolerability of Stereotactic Body Radiotherapy (SBRT) Based on Number of Cumulative Acute Toxicities Occurring Within 90 Days of Treatment and Related to SBRT.
Time frame: 90 days
To determine a tolerable dose, cumulative acute toxicity was collected (defined as toxicity occurring within 90 days of treatment initiation). Adverse events were graded by the Common Terminology Criteria for Adverse Events version 3.0. Tolerability was based on hepatic toxicity. A grading (severity) scale is provided for each adverse event (AE) term. Grade 1 Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2 Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental Activities of Daily Living (ADL). Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL. Grade 4 Life-threatening consequences; urgent intervention indicated. Grade 5 Death related to AE.
3 secondary outcomes
Local Tumor Control to Doses of Radiation in Patients With Liver Cancer or Metastases to the Liver
Time frame: 12.7 months
Percentage of Local Response to Doses of Radiation in Patients With Liver Cancer or Metastases to the Liver
Time frame: 6 months
Overall Survival of Patients With Liver Cancer or Metastases to the Liver
Time frame: 1 year
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Jul 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Website for University of North Carolina Lineberger Comprehensive Cancer CenterLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Joel Tepper, MD principal investigator
University of North Carolina at Chapel Hill Lineberger Comprehensive Cancer Center
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Stereotactic Radiosurgery using the CyberKnife System. in people with Liver Neoplasms and Colonic Neoplasms, run by UNC Lineberger Comprehensive Cancer Center at 2 sites in United States.
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 15 inclusion and 11 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 26 Jul 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. 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.
Are results available for this study?
Yes. Results are posted in the registry (first posted 15 May 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Tolerability of Stereotactic Body Radiotherapy (SBRT) Based on Number of Cumulative Acute Toxicities Occurring Within 90 Days of Treatment and Related to SBRT. (time frame: 90 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 26 Jul 2018.