ClinicalTrials.gg
RecruitingNCT03726359Updated Aug 3, 2026

Phase I Study of Fractionated Stereotactic Radiation Therapy

An interventional study of Fractionated Stereotactic Radiation Therapy (FSRT) in Brain Metastases, sponsored by Albert Einstein College of Medicine. Recruiting at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-08-03.

Sponsored by Albert Einstein College of Medicine · Not applicable, Interventional, and Treatment

From the registry’s dates

  • Registered 10 months after the study started (first participant enrolled Dec 2017, registered Oct 2018).
  • Started Dec 2017; still recruiting 8 years 10 months later.
Phase
Not applicable
Study type
Interventional
Enrollment
43
Allocation
Not applicable
Ages
18 Years and older
Sex
All
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Study 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.

02

Conditions studied

  • Brain Metastases

Browse trials for

03

In context

Brain Neoplasms

2,440 studies on the registry are indexed under Brain Neoplasms; 540 are open to participants now.

This study's planned enrollment of 43 is close to the median of 40 across 1,831 interventional studies indexed under Brain Neoplasms.

Browse Brain Neoplasms studies →

Lead sponsor

Albert Einstein College of Medicine is the lead sponsor of 201 studies on the registry; 21 are open to participants now.

Of its 46 completed or terminated interventional studies of FDA-regulated products, 37 (80%) have results posted.

Counted across the registry records on this site, refreshed daily.

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Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

Inclusion criteria

  • proven diagnosis of a non-hematological other than small cell lung cancer within 5 years of registration
  • Intact (unresected) 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 and male participants must practice adequate
  • History/Physical examination within 30 days prior to registration
  • >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

Exclusion criteria

Exclusion Criteria:

  • Patients with definitive , based on cerebrospinal fluid (CSF) examination
  • Plan for chemotherapy or targeted agents during treatment. Hormonal therapy, immunotherapy targeting /PD-L1 axis, and bone supportive therapy may be continued during treatment
  • to enhanced MRI imaging such as implanted metal devices. However, patients with implanted devices which are MRI compatible are allowed
  • Patients with measurable resulting from small cell lung cancer and germ cell
  • Uncontrolled intercurrent illness such as congestive heart failure, unstable angina, cardiac arrhythmia, and uncontrolled seizure activity
  • Previous treatment of the target lesion with radiotherapy
Terms in these criteria, in plain language(9)

Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.

Histologically or cytologically confirmed

The diagnosis was confirmed by looking at a sample under a microscope: tissue from a biopsy or surgery (histology), or cells from a fluid or needle sample (cytology).

Your pathology report is the document that shows this.

Cancer (malignancy)

Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.

Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.

Brain metastases

Cancer deposits in the brain from a cancer that started elsewhere in the body (CNS metastases include the spinal cord).

Studies differ: some leave out any brain metastases, some accept ones treated and stable for some weeks. Check what this study allows.

Childbearing potential

Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).

Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.

Contraception

Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.

Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.

Life expectancy

The study doctor’s estimate of how long someone is likely to live. Criteria use it so that people can stay in the study long enough for it to answer its question.

Leptomeningeal disease

Cancer that has spread to the leptomeninges, the thin layers covering the brain and spinal cord, and the fluid between them. It is not the same as brain metastases.

Criteria often treat it separately, and many studies leave it out even where treated brain metastases are allowed.

PD-1, PD-L1 and checkpoint inhibitors

PD-1, PD-L1 and CTLA-4 are proteins that act as brakes on the immune system. Checkpoint inhibitors, such as pembrolizumab or nivolumab, block them so the immune system can attack a cancer.

PD-L1 can also be measured in a tumour sample. Some scores count stained tumour cells only (TPS); others also count certain immune cells (CPS). The study names the score and the minimum it uses.

Contraindication

A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.

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Study design

Phase
Not applicable
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
43 participants (estimated)

Study arms

  • Experimental
    Fractionated Stereotactic Radiation Therapy (FSRT)

    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

  • RadiationFractionated Stereotactic Radiation Therapy (FSRT)

    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.

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What researchers measure

Primary outcomes

  1. Maximum Tolerated Dose (MTD)

    Determine the maximum tolerated dose (MTD) associated with a 20% probability of dose limiting toxicity (DLT). DLT is defined as grade 3 or higher toxicities (per CTCAE version 4.03; MedDRA version 12.0) that occur within 1 year of treatment start and are either possibly, probably, or definitively related to radiotherapy (RT), and related to the specific symptoms.

    Time frame: Within 1 year of initiation of treatment

Secondary outcomes

  1. Response to Treatment

    Response to treatment will be assessed based on the percentage of patients who achieve either a complete response (CR), partial response (PR), or stable disease (SD), or progression (P) in response to FSRT treatment. Best response will be summarized. Response criteria will be assessed as follows: Complete Response (CR): Defined as follow up imaging which shows that complete radiographic disappearance of brain metastasis Partial Response (PR): Decrease of \>50% in the size of each lesion radiographically, using perpendicular diameters Stable Disease (SD): 0 to 50% reduction in size of each lesion radiographically, using perpendicular diameters Progression (P): Defined as \> 25% increase in the size of each lesion or a new, non-contiguous lesion developed outside of the radiosurgical volume

    Time frame: Up to 1 year following initiation of treatment

07

Study locations

1 of 1 sites recruiting
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References and documents

Publications

  • 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. PubMed 26282648 ↗
  • 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. PubMed 2405271 ↗
  • 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. PubMed 9809728 ↗
  • 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. PubMed 2725874 ↗
  • 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. PubMed 19801201 ↗
  • 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. PubMed 17401015 ↗
  • 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. PubMed 18448270 ↗
  • 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. PubMed 14701778 ↗
  • 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. PubMed 23956241 ↗
  • 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. PubMed 15158627 ↗
  • 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. PubMed 10487566 ↗
  • 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. PubMed 26181254 ↗
  • 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. PubMed 21041710 ↗
  • 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. PubMed 10802351 ↗
  • 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. PubMed 21575163 ↗
  • 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. PubMed 16776334 ↗
  • 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. PubMed 21311296 ↗
  • 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. PubMed 19783374 ↗
  • 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. PubMed 12788187 ↗
  • 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. PubMed 23759065 ↗
  • 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. PubMed 16978720 ↗
  • 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. PubMed 17960338 ↗
  • 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. PubMed 24439342 ↗
  • 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. PubMed 25059451 ↗
  • 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. PubMed 22429918 ↗
  • 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. PubMed 20800386 ↗
  • 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. PubMed 19132728 ↗
  • 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. PubMed 11261830 ↗
  • 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. PubMed 23205789 ↗
  • 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. PubMed 24488446 ↗
  • 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. PubMed 21316787 ↗
  • 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. PubMed 27936894 ↗

Individual participant data

Plan to share: No

09

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Aug 3, 2026, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
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Registry details

Key details

Study ID
NCT03726359
Responsible party
Sponsor
First posted
Oct 31, 2018
Start date
Dec 25, 2017
Primary completion
Jun 2027 (estimated)
Completion
Jun 2027 (estimated)
Last update
Aug 3, 2026

Study contacts

Nitin Ohri, MD
Contact
nitin.ohri@einsteinmed.edu
718-920-4140
Akash Shah
Contact
ashah1@montefiore.org
718-862-8840
Madhur Garg, MD
principal investigator · Montefiore Medical Center

Oversight

Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
Yes
View the source record on ClinicalTrials.gov ↗

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