Neoplasm Clinical Trial
Official title:
Phase I Trial of Stereotactic Radiosurgery Following Surgical Resection of Intra-axial Brain Metastases
Brain metastases are the most common adult intracranial tumor, occurring in approximately
10% to 30% of adult cancer patients, and represent an important cause of morbidity and
mortality in this population. The standard of care for solitary brain metastasis is surgery
followed by whole brain radiation therapy (WBRT). Without WBRT, there are unacceptably high
levels of local failure that occur. Local recurrence rates ranged from approximately 45% at
1 year to 60% at 2 years after resection alone. However, aside from improvements in
intra-cranial control, it is well documented that WBRT is associated with serious long term
side effects, including significant decline in short term recall by as early as 4 months
after treatment.
Many centers are now offering patients stereotactic radiosurgery (SRS) to the cavity after
resection alone to improve local control while avoiding the negative effects of WBRT. There
have been several retrospective studies on the use of SRS to the resection cavity alone,
from which the 1 year actuarial local control rates range from 35% - 82%. The high rate of
in-field local failure suggests that the current dosing regimen used may not be high enough
for adequate local control. Currently, the highest local control rates are approximately
80%, but there may be room for improvement with increased dose without significantly
increasing the risk of side effects.
The investigators propose a trial for patients after surgical resection of solitary brain
metastases. The purpose of this trial will be to determine the maximum tolerated dose for
single fraction SRS to the resection cavity. There will be three groups based on the
resection cavity size. Dose escalation enrollment will be done sequentially within each
cohort. You will know which cohort and which specific dose level you are randomized to.
After treatment, which will take one day, regardless of cohort, you will be followed closely
for treatment outcome and possible side effects. You will be asked to complete three quick
surveys at each follow-up appointment regarding quality of life and memory in addition to
standard of care surveillance brain MRI and physical exam.
Status | Completed |
Enrollment | 9 |
Est. completion date | October 2015 |
Est. primary completion date | October 2015 |
Accepts healthy volunteers | No |
Gender | Both |
Age group | 18 Years and older |
Eligibility |
Inclusion Criteria: - Pathologic proven diagnosis of solid tumor malignancy - Age = 18 - RPA class I or class II - Mini Mental Status Exam (MMSE) = 18 prior to study entry - Karnofsky Performance Status = 70% - Single brain metastasis status post surgical resection with = 1 cc of residual enhancing tumor - Up to 2 additional intact brain metastases to be treated with stereotactic radiosurgery (SRS) alone - Resection cavity volume on planning scan of = 35 cc - First presentation of brain metastases - Post-operative MRI within 72 hours of surgical resection Exclusion Criteria: - Previous brain radiotherapy (SRS or WBRT) - RPA class III - Resection cavity volume > 35 cc - Radiosensitive or non-solid (eg. small cell lung carcinomas, germ cell tumors, leukemias, or lymphomas) or unknown tumor histologies - Concurrent chemotherapy (no chemotherapy starting 14 days before start of radiation to 14 days after completion of radiation) - Evidence of leptomeningeal disease by MRI and/or CSF cytology - Current pregnancy - More than 8 weeks between resection and radiosurgical procedure - No metastases to brain stem, midbrain, pons, or medulla or within 7 mm of the optic apparatus (optic nerves and chiasm) - Inability to undergo MRI evaluation for treatment planning and follow-up |
Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Country | Name | City | State |
---|---|---|---|
United States | Emory University Hospital | Atlanta | Georgia |
United States | The Emory Clinic | Atlanta | Georgia |
Lead Sponsor | Collaborator |
---|---|
Emory University |
United States,
Arbit E, Wronski M, Burt M, Galicich JH. The treatment of patients with recurrent brain metastases. A retrospective analysis of 109 patients with nonsmall cell lung cancer. Cancer. 1995 Sep 1;76(5):765-73. — View Citation
Chang EL, Wefel JS, Hess KR, Allen PK, Lang FF, Kornguth DG, Arbuckle RB, Swint JM, Shiu AS, Maor MH, Meyers CA. Neurocognition in patients with brain metastases treated with radiosurgery or radiosurgery plus whole-brain irradiation: a randomised controlled trial. Lancet Oncol. 2009 Nov;10(11):1037-44. doi: 10.1016/S1470-2045(09)70263-3. Epub 2009 Oct 2. — View Citation
CHAO JH, PHILLIPS R, NICKSON JJ. Roentgen-ray therapy of cerebral metastases. Cancer. 1954 Jul;7(4):682-9. — View Citation
Gaspar L, Scott C, Rotman M, Asbell S, Phillips T, Wasserman T, McKenna WG, Byhardt R. Recursive partitioning analysis (RPA) of prognostic factors in three Radiation Therapy Oncology Group (RTOG) brain metastases trials. Int J Radiat Oncol Biol Phys. 1997 Mar 1;37(4):745-51. — View Citation
Kocher M, Soffietti R, Abacioglu U, Villà S, Fauchon F, Baumert BG, Fariselli L, Tzuk-Shina T, Kortmann RD, Carrie C, Ben Hassel M, Kouri M, Valeinis E, van den Berge D, Collette S, Collette L, Mueller RP. Adjuvant whole-brain radiotherapy versus observation after radiosurgery or surgical resection of one to three cerebral metastases: results of the EORTC 22952-26001 study. J Clin Oncol. 2011 Jan 10;29(2):134-41. doi: 10.1200/JCO.2010.30.1655. Epub 2010 Nov 1. — View Citation
Mathieu D, Kondziolka D, Flickinger JC, Fortin D, Kenny B, Michaud K, Mongia S, Niranjan A, Lunsford LD. Tumor bed radiosurgery after resection of cerebral metastases. Neurosurgery. 2008 Apr;62(4):817-23; discussion 823-4. doi: 10.1227/01.neu.0000316899.55501.8b. — View Citation
Patchell RA, Regine WF. The rationale for adjuvant whole brain radiation therapy with radiosurgery in the treatment of single brain metastases. Technol Cancer Res Treat. 2003 Apr;2(2):111-5. Review. — View Citation
Patchell RA, Tibbs PA, Regine WF, Dempsey RJ, Mohiuddin M, Kryscio RJ, Markesbery WR, Foon KA, Young B. Postoperative radiotherapy in the treatment of single metastases to the brain: a randomized trial. JAMA. 1998 Nov 4;280(17):1485-9. — View Citation
Roberge D, Souhami L. Tumor bed radiosurgery following resection of brain metastases: a review. Technol Cancer Res Treat. 2010 Dec;9(6):597-602. Review. — View Citation
Soltys SG, Adler JR, Lipani JD, Jackson PS, Choi CY, Puataweepong P, White S, Gibbs IC, Chang SD. Stereotactic radiosurgery of the postoperative resection cavity for brain metastases. Int J Radiat Oncol Biol Phys. 2008 Jan 1;70(1):187-93. Epub 2007 Sep 19. — View Citation
Sundström JT, Minn H, Lertola KK, Nordman E. Prognosis of patients treated for intracranial metastases with whole-brain irradiation. Ann Med. 1998 Jun;30(3):296-9. — View Citation
Wen PY, Loeffler JS. Management of brain metastases. Oncology (Williston Park). 1999 Jul;13(7):941-54, 957-61; discussion 961-2, 9. Review. — View Citation
Zimm S, Wampler GL, Stablein D, Hazra T, Young HF. Intracerebral metastases in solid-tumor patients: natural history and results of treatment. Cancer. 1981 Jul 15;48(2):384-94. — View Citation
* Note: There are 13 references in all — Click here to view all references
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Maximum Tolerated Dose | To assess whether treating a brain resection cavity with this stereotactic radiosurgery is safe and tolerable and to determine the maximum-tolerated radiation dose for SRS to the resection cavity alone with 4-month toxicity as assessed by the RTOG central nervous system (CNS) toxicity scale | 4 months after intervention | Yes |
Secondary | Local Control | Defined as lack of progression of disease in resection cavity as assessed by period MRI scans for up to 2 years after intervention. | up to 2 years after intervention | No |
Secondary | Distant Control | Defined as lack of progression of disease in surrounding brain as assessed by period MRI scans for up to 2 years after intervention | up to 2 years after intervention | No |
Secondary | Neurocognitive Outcomes | Neurocognitive assessment using the Hopkins Verbal Learning Test-Revised (HVLT-R), Mini Mental Status Exam (MMSE) and Cognitive Functioning Subscale of the Medical Outcomes Scale (MOS), administered to the patient periodically for up to 2 years after intervention. | up to 2 years after intervention | No |
Secondary | Quality of Life | Quality of life (QOL) outcomes: using the quality of life questionnaire for the Functional Assessment of Cancer Therapy-Brain (FACT-Br) administered periodically for up to 2 years. | up to 2 years after intervention | No |
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