Phase I Study of Fractionated Stereotactic Radiation Therapy

NCT03726359 | Recruiting Phase 1 DMC FDA Device

• 1 other identifier: 2017-8344
• Study Type: interventional
• Target: 43
• Locations: 1 country
• Sites: 1

Brief Summary

There is a lack of prospective trial data and consensus guidelines describing the use of Fractionated Stereotactic Radiation Therapy (FSRT) in the treatment of brain metastases. There has been no prospective dose escalation study performed to date to determine the maximum tolerated dose (MTD) in patients treated with FSRT. Prescription doses in the series described above ranged from 18 Gy to 42 Gy, delivered in 3 to 12 fractions. The results of this study will be used to plan future Phase II/III studies to determine the efficacy of different dose fractionation schedules of FSRT. The investigator team thus proposes a Phase I study to determine the feasibility and safety of FSRT in patients with brain metastases.

Conditions

Brain Metastases

Outcome Measures

Primary Outcomes (1)

• Maximum Tolerated Dose (MTD)

  Determine the maximum tolerated dose (MTD) associated with a 20% dose limiting toxicity (DLT). DLT is defined as grade 3 or higher toxicities that occur within 1 year of treatment start and either possibly, probably, or definitively related to radiotherapy (RT).

  Within 1 year of initiation of treatment

Secondary Outcomes (1)

• Response to Treatment

  Up to 1 year following initiation of treatment

Study Arms (1)

Fractionated Stereotactic Radiation Therapy (FSRT)

EXPERIMENTAL

This study is unique in that it employs a continuous reassessment methodology (CRM) to determine the Maximum Tolerated Dose. Information for the proper dose level for each subsequent patient enrolled will be determined based on DLTs from previous patients enrolled in the trial.

Radiation: Fractionated Stereotactic Radiation Therapy (FSRT)

Interventions

Fractionated Stereotactic Radiation Therapy (FSRT) RADIATION

Initial starting dose will be 7 Gy x5= 35 Gy delivered to the planning target volume (PTV). Radiotherapy will be delivered every other day so that the Stereotactic Body Radiation Therapy (SBRT) schedule is completed within 1.5-2 weeks.

Fractionated Stereotactic Radiation Therapy (FSRT)

Eligibility Criteria

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

You may qualify if:

• Pathologically proven diagnosis of a non-hematological malignancy other than small cell lung cancer within 5 years of registration
• Intact (unresected) brain metastases measuring ≥3 cm and ≤ 6 cm in largest dimension on gadolinium contrast enhanced MRI obtained within 30 days prior to registration OR Surgically resected brain metastasis for which postoperative stereotactic radiotherapy is indicated, with expected target measuring ≥3 cm and ≤6 cm in largest dimension
• Prior Whole Brain Radiation Therapy (WBRT) is allowed
• Age ≥ 18 years
• Women of childbearing potential and male participants must practice adequate contraception
• History/Physical examination within 30 days prior to registration
• Life expectancy \>3 months
• Patients are allowed to enroll if previously treated to other lesions with Stereotactic Radiosurgery (SRS)
• Patients with multiple lesions are allowed, as long there is one dominant lesion that will be treated with FSRT. Other lesions may be treated concurrently with SRS or FSRT at the discretion of the treating physician but will not contribute to the study endpoints

You may not qualify if:

• Patients with definitive leptomeningeal metastases, based on cerebrospinal fluid (CSF) examination
• Plan for chemotherapy or targeted agents during treatment. Hormonal therapy, immunotherapy targeting PD-1/PD-L1 axis, and bone supportive therapy may be continued during treatment
• Contraindication to enhanced MRI imaging such as implanted metal devices. However, patients with implanted devices which are MRI compatible are allowed
• Patients with measurable brain metastasis resulting from small cell lung cancer and germ cell malignancy
• Uncontrolled intercurrent illness such as congestive heart failure, unstable angina, cardiac arrhythmia, and uncontrolled seizure activity
• Previous treatment of the target lesion with radiotherapy

Sponsors & Collaborators

• Albert Einstein College of Medicine: lead

Study Sites (1)

Montefiore Medical Center

The Bronx, New York, 10467, United States

RECRUITING

Related Publications (32)

• Lin X, DeAngelis LM. Treatment of Brain Metastases. J Clin Oncol. 2015 Oct 20;33(30):3475-84. doi: 10.1200/JCO.2015.60.9503. Epub 2015 Aug 17.

  PMID: 26282648 BACKGROUND

• Patchell RA, Tibbs PA, Walsh JW, Dempsey RJ, Maruyama Y, Kryscio RJ, Markesbery WR, Macdonald JS, Young B. A randomized trial of surgery in the treatment of single metastases to the brain. N Engl J Med. 1990 Feb 22;322(8):494-500. doi: 10.1056/NEJM199002223220802.

  PMID: 2405271 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.

  PMID: 9809728 BACKGROUND

• DeAngelis LM, Delattre JY, Posner JB. Radiation-induced dementia in patients cured of brain metastases. Neurology. 1989 Jun;39(6):789-96. doi: 10.1212/wnl.39.6.789.

  PMID: 2725874 BACKGROUND

• 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

• Li J, Bentzen SM, Renschler M, Mehta MP. Regression after whole-brain radiation therapy for brain metastases correlates with survival and improved neurocognitive function. J Clin Oncol. 2007 Apr 1;25(10):1260-6. doi: 10.1200/JCO.2006.09.2536.

  PMID: 17401015 BACKGROUND

• Welzel G, Fleckenstein K, Schaefer J, Hermann B, Kraus-Tiefenbacher U, Mai SK, Wenz F. Memory function before and after whole brain radiotherapy in patients with and without brain metastases. Int J Radiat Oncol Biol Phys. 2008 Dec 1;72(5):1311-8. doi: 10.1016/j.ijrobp.2008.03.009. Epub 2008 Apr 28.

  PMID: 18448270 BACKGROUND

• Meyers CA, Smith JA, Bezjak A, Mehta MP, Liebmann J, Illidge T, Kunkler I, Caudrelier JM, Eisenberg PD, Meerwaldt J, Siemers R, Carrie C, Gaspar LE, Curran W, Phan SC, Miller RA, Renschler MF. Neurocognitive function and progression in patients with brain metastases treated with whole-brain radiation and motexafin gadolinium: results of a randomized phase III trial. J Clin Oncol. 2004 Jan 1;22(1):157-65. doi: 10.1200/JCO.2004.05.128.

  PMID: 14701778 BACKGROUND

• Brown PD, Pugh S, Laack NN, Wefel JS, Khuntia D, Meyers C, Choucair A, Fox S, Suh JH, Roberge D, Kavadi V, Bentzen SM, Mehta MP, Watkins-Bruner D; Radiation Therapy Oncology Group (RTOG). Memantine for the prevention of cognitive dysfunction in patients receiving whole-brain radiotherapy: a randomized, double-blind, placebo-controlled trial. Neuro Oncol. 2013 Oct;15(10):1429-37. doi: 10.1093/neuonc/not114. Epub 2013 Aug 16.

  PMID: 23956241 BACKGROUND

• Andrews DW, Scott CB, Sperduto PW, Flanders AE, Gaspar LE, Schell MC, Werner-Wasik M, Demas W, Ryu J, Bahary JP, Souhami L, Rotman M, Mehta MP, Curran WJ Jr. Whole brain radiation therapy with or without stereotactic radiosurgery boost for patients with one to three brain metastases: phase III results of the RTOG 9508 randomised trial. Lancet. 2004 May 22;363(9422):1665-72. doi: 10.1016/S0140-6736(04)16250-8.

  PMID: 15158627 BACKGROUND

• Kondziolka D, Patel A, Lunsford LD, Kassam A, Flickinger JC. Stereotactic radiosurgery plus whole brain radiotherapy versus radiotherapy alone for patients with multiple brain metastases. Int J Radiat Oncol Biol Phys. 1999 Sep 1;45(2):427-34. doi: 10.1016/s0360-3016(99)00198-4.

  PMID: 10487566 BACKGROUND

• Aoyama H, Tago M, Shirato H; Japanese Radiation Oncology Study Group 99-1 (JROSG 99-1) Investigators. Stereotactic Radiosurgery With or Without Whole-Brain Radiotherapy for Brain Metastases: Secondary Analysis of the JROSG 99-1 Randomized Clinical Trial. JAMA Oncol. 2015 Jul;1(4):457-64. doi: 10.1001/jamaoncol.2015.1145.

  PMID: 26181254 BACKGROUND

• 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.

  PMID: 21041710 BACKGROUND

• Shaw E, Scott C, Souhami L, Dinapoli R, Kline R, Loeffler J, Farnan N. Single dose radiosurgical treatment of recurrent previously irradiated primary brain tumors and brain metastases: final report of RTOG protocol 90-05. Int J Radiat Oncol Biol Phys. 2000 May 1;47(2):291-8. doi: 10.1016/s0360-3016(99)00507-6.

  PMID: 10802351 BACKGROUND

• Minniti G, Clarke E, Lanzetta G, Osti MF, Trasimeni G, Bozzao A, Romano A, Enrici RM. Stereotactic radiosurgery for brain metastases: analysis of outcome and risk of brain radionecrosis. Radiat Oncol. 2011 May 15;6:48. doi: 10.1186/1748-717X-6-48.

  PMID: 21575163 BACKGROUND

• Vogelbaum MA, Angelov L, Lee SY, Li L, Barnett GH, Suh JH. Local control of brain metastases by stereotactic radiosurgery in relation to dose to the tumor margin. J Neurosurg. 2006 Jun;104(6):907-12. doi: 10.3171/jns.2006.104.6.907.

  PMID: 16776334 BACKGROUND

• Yang HC, Kano H, Lunsford LD, Niranjan A, Flickinger JC, Kondziolka D. What factors predict the response of larger brain metastases to radiosurgery? Neurosurgery. 2011 Mar;68(3):682-90; discussion 690. doi: 10.1227/NEU.0b013e318207a58b.

  PMID: 21311296 BACKGROUND

• Blonigen BJ, Steinmetz RD, Levin L, Lamba MA, Warnick RE, Breneman JC. Irradiated volume as a predictor of brain radionecrosis after linear accelerator stereotactic radiosurgery. Int J Radiat Oncol Biol Phys. 2010 Jul 15;77(4):996-1001. doi: 10.1016/j.ijrobp.2009.06.006. Epub 2009 Sep 23.

  PMID: 19783374 BACKGROUND

• Aoyama H, Shirato H, Onimaru R, Kagei K, Ikeda J, Ishii N, Sawamura Y, Miyasaka K. Hypofractionated stereotactic radiotherapy alone without whole-brain irradiation for patients with solitary and oligo brain metastasis using noninvasive fixation of the skull. Int J Radiat Oncol Biol Phys. 2003 Jul 1;56(3):793-800. doi: 10.1016/s0360-3016(03)00014-2.

  PMID: 12788187 BACKGROUND

• Eaton BR, Gebhardt B, Prabhu R, Shu HK, Curran WJ Jr, Crocker I. Hypofractionated radiosurgery for intact or resected brain metastases: defining the optimal dose and fractionation. Radiat Oncol. 2013 Jun 7;8:135. doi: 10.1186/1748-717X-8-135.

  PMID: 23759065 BACKGROUND

• Ernst-Stecken A, Ganslandt O, Lambrecht U, Sauer R, Grabenbauer G. Phase II trial of hypofractionated stereotactic radiotherapy for brain metastases: results and toxicity. Radiother Oncol. 2006 Oct;81(1):18-24. doi: 10.1016/j.radonc.2006.08.024. Epub 2006 Sep 15.

  PMID: 16978720 BACKGROUND

• Fahrig A, Ganslandt O, Lambrecht U, Grabenbauer G, Kleinert G, Sauer R, Hamm K. Hypofractionated stereotactic radiotherapy for brain metastases--results from three different dose concepts. Strahlenther Onkol. 2007 Nov;183(11):625-30. doi: 10.1007/s00066-007-1714-1.

  PMID: 17960338 BACKGROUND

• Feuvret L, Vinchon S, Martin V, Lamproglou I, Halley A, Calugaru V, Chea M, Valery CA, Simon JM, Mazeron JJ. Stereotactic radiotherapy for large solitary brain metastases. Cancer Radiother. 2014 Mar;18(2):97-106. doi: 10.1016/j.canrad.2013.12.003. Epub 2014 Jan 14.

  PMID: 24439342 BACKGROUND

• Rajakesari S, Arvold ND, Jimenez RB, Christianson LW, Horvath MC, Claus EB, Golby AJ, Johnson MD, Dunn IF, Lee EQ, Lin NU, Friesen S, Mannarino EG, Wagar M, Hacker FL, Weiss SE, Alexander BM. Local control after fractionated stereotactic radiation therapy for brain metastases. J Neurooncol. 2014 Nov;120(2):339-46. doi: 10.1007/s11060-014-1556-5. Epub 2014 Jul 25.

  PMID: 25059451 BACKGROUND

• Jiang XS, Xiao JP, Zhang Y, Xu YJ, Li XP, Chen XJ, Huang XD, Yi JL, Gao L, Li YX. Hypofractionated stereotactic radiotherapy for brain metastases larger than three centimeters. Radiat Oncol. 2012 Mar 19;7:36. doi: 10.1186/1748-717X-7-36.

  PMID: 22429918 BACKGROUND

• Kim YJ, Cho KH, Kim JY, Lim YK, Min HS, Lee SH, Kim HJ, Gwak HS, Yoo H, Lee SH. Single-dose versus fractionated stereotactic radiotherapy for brain metastases. Int J Radiat Oncol Biol Phys. 2011 Oct 1;81(2):483-9. doi: 10.1016/j.ijrobp.2010.05.033. Epub 2010 Aug 26.

  PMID: 20800386 BACKGROUND

• Kwon AK, Dibiase SJ, Wang B, Hughes SL, Milcarek B, Zhu Y. Hypofractionated stereotactic radiotherapy for the treatment of brain metastases. Cancer. 2009 Feb 15;115(4):890-8. doi: 10.1002/cncr.24082.

  PMID: 19132728 BACKGROUND

• Lederman G, Wronski M, Fine M. Fractionated radiosurgery for brain metastases in 43 patients with breast carcinoma. Breast Cancer Res Treat. 2001 Jan;65(2):145-54. doi: 10.1023/a:1006490200335.

  PMID: 11261830 BACKGROUND

• Ma LH, Li G, Zhang HW, Wang ZY, Dang J, Zhang S, Yao L, Zhang XM. Hypofractionated stereotactic radiotherapy with or without whole-brain radiotherapy for patients with newly diagnosed brain metastases from non-small cell lung cancer. J Neurosurg. 2012 Dec;117 Suppl:49-56. doi: 10.3171/2012.7.GKS121071.

  PMID: 23205789 BACKGROUND

• Minniti G, D'Angelillo RM, Scaringi C, Trodella LE, Clarke E, Matteucci P, Osti MF, Ramella S, Enrici RM, Trodella L. Fractionated stereotactic radiosurgery for patients with brain metastases. J Neurooncol. 2014 Apr;117(2):295-301. doi: 10.1007/s11060-014-1388-3. Epub 2014 Feb 1.

  PMID: 24488446 BACKGROUND

• Wiggenraad R, Verbeek-de Kanter A, Kal HB, Taphoorn M, Vissers T, Struikmans H. Dose-effect relation in stereotactic radiotherapy for brain metastases. A systematic review. Radiother Oncol. 2011 Mar;98(3):292-7. doi: 10.1016/j.radonc.2011.01.011.

  PMID: 21316787 BACKGROUND

• Baliga S, Garg MK, Fox J, Kalnicki S, Lasala PA, Welch MR, Tome WA, Ohri N. Fractionated stereotactic radiation therapy for brain metastases: a systematic review with tumour control probability modelling. Br J Radiol. 2017 Feb;90(1070):20160666. doi: 10.1259/bjr.20160666. Epub 2016 Dec 12.

  PMID: 27936894 BACKGROUND

MeSH Terms

Conditions

Brain Neoplasms

Condition Hierarchy (Ancestors)

Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Study Officials

• Madhur Garg, MD

  Montefiore Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Nitin Ohri, MD

CONTACT

718-920-4140; nitin.ohri@einsteinmed.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 30, 2018
• First Posted: October 31, 2018
• Study Start: December 25, 2017
• Primary Completion (Estimated): May 1, 2027
• Study Completion (Estimated): May 1, 2027
• Last Updated: May 22, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)