Stereotactic Radiation Therapy in Treating Patients With Liver Metastases

A Phase I/II Dose-Finding Study of Single-Fraction Stereotactic Body Radiotherapy (SF-SBRT) for the Treatment of Liver Metastases

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.

Study Overview

• Status: Terminated
• Conditions: Unspecified Adult Solid Tumor
• Intervention / Treatment: Radiation: stereotactic radiation therapy; Procedure: implanted fiducial-based imaging; Procedure: cone-beam computed tomography

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.

• Study Type: Interventional
• Enrollment (Actual): 3
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 120 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Radiation: stereotactic radiation therapy; Patients undergo stereotactic body radiation therapy; Procedure: implanted fiducial-based imaging; radiation therapy treatment planning; Procedure: cone-beam computed tomography; radiation therapy treatment planning

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)	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.	At 1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	Up to 2 years
Patient Clinical Response and Treatment Effects on Blood Chemistry and Hepatic Function Markers (Phase I)		Up to 2 years
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
Refinement of Toxicity and Adverse Events Profile (Phase II)		Up to 2 years
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

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Investigators: Study Chair: Robert C. Miller, M.D., Mayo Clinic

Study record dates

Study Major Dates

• Study Start: July 1, 2009
• Primary Completion (Actual): April 1, 2011

Study Registration Dates

• First Submitted: July 9, 2009
• First Submitted That Met QC Criteria: July 10, 2009
• First Posted (Estimate): July 13, 2009

Study Record Updates

• Last Update Posted (Estimate): May 19, 2016
• Last Update Submitted That Met QC Criteria: April 19, 2016
• Last Verified: October 1, 2015

More Information

Terms related to this study

• Keywords: protocol specific
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Neoplastic Processes; Neoplasm Metastasis
• Other Study ID Numbers: MC0941 (Other Identifier: Mayo Clinic Cancer Center); 09-000020 (Other Identifier: Mayo Clinic IRB); NCI-2009-01150 (Registry Identifier: NCI's CTRO)