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Optimal Planning Target Volume With Stereotactic Radiosurgery

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Duke University
ClinicalTrials.gov Identifier:
NCT01017497
First received: November 19, 2009
Last updated: October 23, 2014
Last verified: September 2014
  Purpose

The purpose of this study is to estimate the rate of local control at the treated site of the metastasis as a function of 1mm versus 3mm expansion about the gross tumor volume (GTV). Each lesion, not each patient will be ranndomized to either the 1mm or 3mm margin with 40 lesions randomized to each arm.


Condition Intervention
Brain Neoplasms
Brain Cancer
Radiation: Stereotactic Radiosurgery

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Determination of the Optimal Planning Target Volume for Brain Metastases Treated With Stereotactic Radiosurgery

Resource links provided by NLM:


Further study details as provided by Duke University:

Primary Outcome Measures:
  • 12-month Local Control Rate [ Time Frame: 12 months after SRS ] [ Designated as safety issue: No ]
    The 12-month local control rate is the percentage of lesions without recurrence at the lesion site 12 months after SRS. Time to local recurrence was defined as the time between SRS and local recurrence. If local recurrence did not occur, the time to local recurrence was censored at last follow-up (including deaths without local recurrence). Kaplan-Meier methods were used to describe the time to local recurrence.


Secondary Outcome Measures:
  • Rate of Radionecrosis at SRS Treatment Site [ Time Frame: 24 months after SRS ] [ Designated as safety issue: No ]
    The rate of radionecrosis is defined as the proportion of lesions with an indication of radiation-associated changes but no evidence of viable tumor on follow-up imaging (and confirmed by tissue biopsy whenever possible).

  • 12 Month Rate of Distant Brain Metastases [ Time Frame: 12 month after SRS ] [ Designated as safety issue: No ]
    The 12-month rate of distant brain metastases is defined as the percentage of participants with the appearance of new brain metastasis located away from the previously treated lesion (i.e. distant brain failure) 12 months after SRS. Time to the appearance of new brain metastasis was defined as the time between SRS and distant brain failure. Patients without new distant brain metastases as of the last follow-up were censored at the last follow-up date. Kaplan-Meier methods were used to describe the time to distant brain failure.

  • Median Overall Survival [ Time Frame: 24 months after SRS ] [ Designated as safety issue: No ]
    Overall survival was defined as the time in months from the start of SRS to the date of death or last contact if alive. Kaplan-Meier methods were used to estimate overall survival.

  • Quality of Life at 3 Months After SRS as Measured by the Functional Assessment of Cancer Therapy-Brain (FACT-Br) [ Time Frame: Baseline to 3 months after SRS ] [ Designated as safety issue: No ]
    Quality of life as measured by the change in FACT-Br scores from baseline to 3 months after SRS. The FACT-Br (version 4) is comprised of the Functional Assessment of Cancer Therapy-General (FACT-G), a 27-item core questionnaire evaluating the domains of physical, family/social, emotional and functional well-being, with the addition of 23 brain cancer specific questions. The FACT-G total score is the sum of the four FACT-G domain scores. The Brain Cancer Subscale (BrCS) is the sum of 19 brain cancer specific questions. The FACT-Br Trial Outcome Index (TOI) is the sum of the BrCS score and the physical and family/social domain scores. The FACT-Br total score is the sum of the FACT-G total score and the BrCS score. Change score = score at 3 months after SRS - score at baseline. Positive change scores indicate improved quality of life.

  • Cognition at 3 Months After SRS as Measured by the Mini-Mental State Exam (MMSE) [ Time Frame: Baseline to 3 months after SRS ] [ Designated as safety issue: No ]
    Cognition as measured by the change in MMSE scores from baseline to 3 months after SRS. The MMSE is an 11-item measure that tests five areas of cognitive function: orientation, registration, attention and calculation, recall and language. The minimum score is 0 and teh maximum score is 30 with higher MMSe scores indicating better cognition. Change score = score at 3 months after SRS - score at baseline. Positive change scores indicate improved cognition.

  • Cognition at 3 Months After SRS as Measured by the Trail Making Test (TMT) [ Time Frame: Baseline to 3 months after SRS ] [ Designated as safety issue: No ]
    Cognition as measured by the change in scores on the Trail Making Test (TMT) from baseline to 3 months after SRS. The TMT consists of two parts. Part A (TMT-A) requires an individual to draw lines sequentially connecting 25 encircled numbers distributed on a sheet of paper. Task requirements are similar for Part B (TMT-B) except the person must alternate between numbers and letters (e.g., 1, A, 2, B, 3, C, etc.). The score on each part represents the amount of time required to complete the task. Change score = score at 3 months after SRS - score at baseline. Negative change scores indicate improved cognition.

  • Rate of Death Due to Neurologic Causes [ Time Frame: 24 months after SRS ] [ Designated as safety issue: Yes ]
    The rate of death due to neurologic causes is defined as the percentage of participants whose death is attributable to the progression of neurological disease.


Enrollment: 49
Study Start Date: December 2009
Study Completion Date: December 2013
Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1mm margin
GTV expanded by 1 mm
Radiation: Stereotactic Radiosurgery
PTV Diameter < 2.0 cm receives 24 Gy; PTV Diameter 2.0-3.0 cm receives 18 Gy; PTV Diameter 3.1-4.0 cm receives 15 Gy;
Experimental: 3mm margin
GTV expanded by 3 mm
Radiation: Stereotactic Radiosurgery
PTV Diameter < 2.0 cm receives 24 Gy; PTV Diameter 2.0-3.0 cm receives 18 Gy; PTV Diameter 3.1-4.0 cm receives 15 Gy;

Detailed Description:

Stereotactic radiosurgery (SRS) is used either as definitive treatment alone or as a "boost" in combination with whole-brain radiotherapy (WBRT) for the treatment of brain metastases. To establish a target for SRS, the gross tumor volume (GTV) is typically defined as the contrast-enhancing volume on T1-weighted axial MRI images. In turn, the volume chosen for treatment (the planning target volume or PTV) is generated by expanding the GTV to account for microscopic extension of tumor beyond the MRI-visualized volume and deviations in patient positioning at the time of treatment., However, the optimal PTV in patients undergoing SRS of brain metastases has not been established.

This pilot randomized study of approximately 49 patients (representing a total of 80 brain lesions) should be sufficient to explore the effect of margin expansion around the GTV for brain metastases. The patients enrolled in this study will undergo radiosurgery to a planning treatment volume generated by expanding the GTV of each lesion by either a 1mm or 3mm margin. Each lesion, not each patient, will be randomized to receive either the 1mm or 3mm margin with 40 lesions randomized to each arm (a patient with multiple lesions potentially could have a lesion randomized to the 1mm arm and a different lesion randomized to the 3mm arm). The primary outcome of 12-month local recurrence and the secondary outcome of the rate of radionecrosis at the SRS treatment site will be lesion-specific outcomes. All other secondary outcomes will be patient-specific outcomes.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age >18 years
  • Life expectancy of at least 6 months.
  • Karnofsky Performance Score greater than 70
  • Graded prognostic assessment (GPA score 0.5 or greater
  • 1 to 3 brain metastases unresectable
  • Maximum tumor diameter no larger than 4cm

Exclusion Criteria:

  • Primary lesion with radiosensitive histology (such as: small cell carcinoma, germ-cell tumors, lymphoma, leukemia, and multiple myeloma.
  • Metastases in the brain stem, pons or medulla or within 5 mm of optic apparatus
  • Previous cranial radiation
  • Pregnancy
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01017497

Locations
United States, North Carolina
Duke University Medical Center
Durham, North Carolina, United States, 27710
Sponsors and Collaborators
Duke University
Investigators
Principal Investigator: John Kirkpatrick, MD, PhD Duke University Medical Center, Radiation Oncology
  More Information

No publications provided

Responsible Party: Duke University
ClinicalTrials.gov Identifier: NCT01017497     History of Changes
Other Study ID Numbers: Pro00017062
Study First Received: November 19, 2009
Results First Received: September 30, 2014
Last Updated: October 23, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Duke University:
Brain Metastases

Additional relevant MeSH terms:
Brain Neoplasms
Brain Diseases
Central Nervous System Diseases
Central Nervous System Neoplasms
Neoplasms
Neoplasms by Site
Nervous System Diseases
Nervous System Neoplasms

ClinicalTrials.gov processed this record on November 25, 2014