Phase I Trial of Stereotactic Radiosurgery Following Surgical Resection of Brain Metastases

NCT01395407 | Completed Phase 1 DMC

• 2 other identifiers: IRB00049695RADONC1962-11
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Brain Metastasis; Neoplasm

Keywords

Brain; Neoplasm; Neoplasm Metastasis; Radiosurgery

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (4)

• Local Control

  up to 2 years after intervention

• Distant Control

  up to 2 years after intervention

• Neurocognitive Outcomes

  up to 2 years after intervention

• Quality of Life

  up to 2 years after intervention

Study Arms (3)

Cohort A

EXPERIMENTAL

Cohort A: resection cavity volume up to 4.2 cc (corresponds to 0 - 2 cm diameter). Dose level Cohort A (Gy) 1. 21 2. 23 3. 25

Radiation: Radiosurgery dose escalation

Cohort B

EXPERIMENTAL

Cohort B: resection cavity volume \> 4.2 cc and ≤ 14.1 cc (2 - 3 cm diameter). Dose level Cohort B (Gy) 1. 18 2. 20 3. 22

Radiation: Radiosurgery dose escalation

Cohort C

EXPERIMENTAL

Cohort C: resection cavity volume \> 14.1 cc and ≤ 35 cc (3 - 4 cm diameter). Dose level Cohort C (Gy) 1. 15 2. 17 3. 19

Radiation: Radiosurgery dose escalation

Interventions

Radiosurgery dose escalation RADIATION

Cohort A: resection cavity volume up to 4.2 cc (corresponds to 0 - 2 cm diameter). Cohort B: resection cavity volume \> 4.2 cc and ≤ 14.1 cc (2 - 3 cm diameter) Cohort C: resection cavity volume \> 14.1 cc and ≤ 35 cc (3 - 4 cm diameter) Dose level Cohort A (Gy) Cohort B (Gy) Cohort C (Gy) 1. 21 18 15 2. 23 20 17 3. 25 22 19

Cohort A; Cohort B; Cohort C

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Emory University: lead

Study Sites (2)

Emory University Hospital

Atlanta, Georgia, 30322, United States

Location

The Emory Clinic

Atlanta, Georgia, 30322, United States

Location

Related Publications (13)

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  PMID: 9128946 BACKGROUND

• 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. doi: 10.1177/153303460300200206.

  PMID: 12680791 BACKGROUND

• 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. doi: 10.1002/1097-0142(19950901)76:53.0.co;2-e.

  PMID: 8625178 BACKGROUND

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  PMID: 10442342 BACKGROUND

• 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. doi: 10.1001/jama.280.17.1485.

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• Kocher M, Soffietti R, Abacioglu U, Villa 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.

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• 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.

  PMID: 19801201 BACKGROUND

• 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.

  PMID: 18414136 BACKGROUND

• 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. doi: 10.1016/j.ijrobp.2007.06.068. Epub 2007 Sep 19.

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• Roberge D, Souhami L. Tumor bed radiosurgery following resection of brain metastases: a review. Technol Cancer Res Treat. 2010 Dec;9(6):597-602. doi: 10.1177/153303461000900608.

  PMID: 21070082 BACKGROUND

MeSH Terms

Conditions

Brain Neoplasms; Neoplasms; Neoplasm Metastasis

Condition Hierarchy (Ancestors)

Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Ian Crocker, MD

  Emory University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: July 14, 2011
• First Posted: July 15, 2011
• Study Start: July 1, 2011
• Primary Completion: October 1, 2015
• Study Completion: October 1, 2015
• Last Updated: December 3, 2015

Record last verified: 2015-12

Locations

US (2)