Optimal Planning Target Volume With Stereotactic Radiosurgery

Brain Cancer Clinical Trial

Official title:

Determination of the Optimal Planning Target Volume for Brain Metastases Treated With Stereotactic Radiosurgery

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01017497
• Other study ID #: Pro00017062
• Status: Completed
• Phase: N/A
• First received: November 19, 2009
• Last updated: January 27, 2015
• Start date: December 2009
• Est. completion date: December 2013

Study information

• Verified date: January 2015
• Source: Duke University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 49
• Est. completion date: December 2013
• Est. primary completion date: December 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Brain Cancer
• Brain Neoplasms

Intervention

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;

Locations

Country	Name	City	State
United States	Duke University Medical Center	Durham	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Duke University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	12-month Local Control Rate	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.	12 months after SRS	No
Secondary	Rate of Radionecrosis at SRS Treatment Site	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).	24 months after SRS	No
Secondary	12 Month Rate of Distant Brain Metastases	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.	12 month after SRS	No
Secondary	Median Overall Survival	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.	24 months after SRS	No
Secondary	Quality of Life at 3 Months After SRS as Measured by the Functional Assessment of Cancer Therapy-Brain (FACT-Br)	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.	Baseline to 3 months after SRS	No
Secondary	Cognition at 3 Months After SRS as Measured by the Mini-Mental State Exam (MMSE)	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.	Baseline to 3 months after SRS	No
Secondary	Cognition at 3 Months After SRS as Measured by the Trail Making Test (TMT)	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.	Baseline to 3 months after SRS	No
Secondary	Rate of Death Due to Neurologic Causes	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.	24 months after SRS	Yes