Unspecified Adult Solid Tumor
Conditions
Keywords
protocol specific
Brief summary
RATIONALE: Stereotactic radiation therapy may be able to send x-rays directly to the tumor and cause less damage to normal tissue. PURPOSE: This phase I/II trial is studying the side effects and best dose of stereotactic radiation therapy in treating patients with liver metastases.
Detailed description
OUTLINE: This is a phase I/II, dose-escalation study. Phase I: Patients undergo either percutaneous placement of metallic fiducial markers within the liver or respiratory-correlated cone-beam computed tomography for stereotactic targeting and planning. Patients then undergo single-fraction stereotactic body radiotherapy over approximately 1 hour within 1 week of the marker placement. Phase II: Patients undergo treatment as in phase I at the maximum tolerated dose. After completion of study treatment, patients will be followed at weeks 4 and 12 and then every 3 months for 2 years. PROJECTED ACCRUAL: A total of 60 patients will be accrued for this study.
Interventions
PROCEDUREcone-beam computed tomography
radiation therapy treatment planning
RADIATIONstereotactic radiation therapy
Patients undergo stereotactic body radiation therapy
PROCEDUREimplanted fiducial-based imaging
radiation therapy treatment planning
Sponsors
Mayo Clinic
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 120 Years
Healthy volunteers
No
Inclusion criteria
* Histological confirmation (any histology except lymphoma, leukemia, or hepatocellular carcinoma) of at least one liver lesion that is synchronous to the primary diagnosis of malignancy or metachronous as a recurrence/metastasis or as a failure following previous therapy (except radiotherapy). * One to three metastatic liver lesions =\< 5 cm in dimension. * Intrahepatic cholangiocarcinoma is acceptable for inclusion. * Zubrod Performance Status (PS) 0 or 1. * Please contact study investigator and/or consult protocol document for specific details on laboratory criteria. * Life expectancy \>= 12 weeks. * MELD (Model for End-Stage Liver Disease) score =\< 16. * \>= 1000 cc of uninvolved liver parenchyma as determined by the treating physician. * Determination that the patient is medically inoperable and/or unwilling to undergo liver resection in patients with colorectal carcinoma histology. * Provide informed written consent. * Willingness to return to Mayo Clinic Rochester for follow-up.
Exclusion criteria
* Pregnant women. * Nursing women. * Men or women of childbearing potential or their partners who are unwilling to employ adequate contraception. * Co-morbid systemic illnesses or other severe concurrent disease, defined as those which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens Immunocompromised patients (other than that related to the use of corticosteroids) including patients known to be HIV positive. * Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. * Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm =\< 7 days prior to registration. * Administration of chemotherapy within 2 wks prior to or 2 wks following SF-SBRT. * Prior radiation therapy to the liver Untreated malignant biliary obstruction (patients treated successfully with stenting are eligible). * Current diagnosis of hepatocellular carcinoma
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Determination of the Maximum Tolerated Dose (MTD) of Single-fraction Stereotactic Body Radiation Therapy (SF-SBRT) in Hepatic Metastases. | 2 months | — |
| Determine the Minimum Effective Dose (MED) Necessary for Durable Local Control, Defined as the Dose Level at Which Local Control (LC) is >= 80% at 1 Year. (Phase II) | At 1 year | LC is defined as no evidence of disease progression within the volume treated to prescription dose (i.e. PTV) for a specific lesion. The development of new intrahepatic metastases sites outside of the PTV will not be considered local failures. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Radiographic Response Rate (Phase II) | Up to 2 years | — |
| Local Control (LC) Cumulative Incidence Rates (Phase II) | 3 and 6 months and 1, 2, and 5 years | — |
| Median Time to Progression of Treated Tumors (Phase II) | Up to 5 years | — |
| Toxicity and Adverse Events Profile (Phase I) | Up to 2 years | Number of patients with a grade \>= 3 adverse event. Adverse events were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 3. Description of Grades: Grade 1: Mild Grade 2: Moderate Grade 3: Severe Grade 4: Life-threatening Grade 5: Death |
| Refinement of Patient Clinical Response and Treatment Effects on Blood Chemistry and Hepatic Function Markers (Phase II) | Up to 2 years | — |
| Evaluation of Cause of Death (Phase II) | Up to 5 years | — |
| Refinement of Toxicity and Adverse Events Profile (Phase II) | Up to 2 years | — |
| Patient Clinical Response and Treatment Effects on Blood Chemistry and Hepatic Function Markers (Phase I) | Up to 2 years | — |
Countries
United States
Participant flow
Recruitment details
Three patients were recruited at Mayo Clinic between January 2010 and May 2010.
Pre-assignment details
This was a phase I/II trial. A total of 3 participants were accrued, all to the phase I portion. This trial was terminated due to poor accrual. No patients were accrued to the phase II portion. No results from the phase II portion are available.
Participants by arm
| Arm | Count |
|---|---|
| Arm I Patients undergo either percutaneous placement of metallic fiducial markers within the liver or respiratory-correlated cone-beam computed tomography for stereotactic targeting and planning. Patients then undergo single-fraction stereotactic body radiotherapy over approximately 1 hour within 1 week of the marker placement. | 3 |
| Total | 3 |
Baseline characteristics
| Characteristic | Arm I |
|---|---|
| Age, Continuous | 60 years |
| Region of Enrollment United States | 3 participants |
| Sex: Female, Male Female | 1 Participants |
| Sex: Female, Male Male | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 2 / 3 |
| serious Total, serious adverse events | 0 / 3 |
Outcome results
Primary
Determination of the Maximum Tolerated Dose (MTD) of Single-fraction Stereotactic Body Radiation Therapy (SF-SBRT) in Hepatic Metastases.
Time frame: 2 months
Population: Not enough patients were accrued to the Phase I portion to determine the MTD.
Primary
Determine the Minimum Effective Dose (MED) Necessary for Durable Local Control, Defined as the Dose Level at Which Local Control (LC) is >= 80% at 1 Year. (Phase II)
LC is defined as no evidence of disease progression within the volume treated to prescription dose (i.e. PTV) for a specific lesion. The development of new intrahepatic metastases sites outside of the PTV will not be considered local failures.
Time frame: At 1 year
Population: No patients were accrued to the Phase II portion.
Secondary
Evaluation of Cause of Death (Phase II)
Time frame: Up to 5 years
Population: No patients were accrued to the Phase II portion.
Secondary
Local Control (LC) Cumulative Incidence Rates (Phase II)
Time frame: 3 and 6 months and 1, 2, and 5 years
Population: No patients were accrued to the Phase II portion.
Secondary
Median Time to Progression of Treated Tumors (Phase II)
Time frame: Up to 5 years
Population: No patients were accrued to the Phase II portion.
Secondary
Patient Clinical Response and Treatment Effects on Blood Chemistry and Hepatic Function Markers (Phase I)
Time frame: Up to 2 years
Secondary
Radiographic Response Rate (Phase II)
Time frame: Up to 2 years
Population: No patients were accrued to the Phase II portion.
Secondary
Refinement of Patient Clinical Response and Treatment Effects on Blood Chemistry and Hepatic Function Markers (Phase II)
Time frame: Up to 2 years
Population: No patients were accrued to the Phase II portion.
Secondary
Refinement of Toxicity and Adverse Events Profile (Phase II)
Time frame: Up to 2 years
Population: No patients were accrued to the Phase II portion.
Secondary
Toxicity and Adverse Events Profile (Phase I)
Number of patients with a grade \>= 3 adverse event. Adverse events were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 3. Description of Grades: Grade 1: Mild Grade 2: Moderate Grade 3: Severe Grade 4: Life-threatening Grade 5: Death
Time frame: Up to 2 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm I | Toxicity and Adverse Events Profile (Phase I) | 0 participants |