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NCT Number: NCT02747303

Frameless Stereotactic Radiosurgery for Intact Brain Metastases

This is a randomized study to determine if not treating planning target volume (PTV) margins during radiation therapy worsens progression free survival rates in patients with brain metastases.

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Key information

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

University of Chicago

Chicago, Illinois, 60637, United States

Location status: Recruiting

Location contact

Robyn Hseu

CONTACT

[email protected]

Steven J. Chmura, M.D., Ph.D.

PRINCIPAL_INVESTIGATOR

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Adult patients (≥ 18 years old) with an ECOG Performance Status 0-2 and a life expectancy of 3 months or more.
  • Histologically confirmed systemic malignancy with gadolinium contrast-enhanced MRI scan demonstrating 1-5 intraparenchymal brain metastases.
  • Well-circumscribed, measureable intraparenchymal brain lesion(s) with maximum tumor diameter ≤3.0 cm. If multiple lesions are present, the other(s) must not exceed 3.0 cm in maximum diameter. At least one lesion must be ≥1.0 cm in maximum diameter and ≥0.5 cm in a perpendicular diameter to be considered measurable disease.
  • Negative urine or serum pregnancy test done ≤ 14 days prior to CT simulation, for women of child-bearing potential only.
  • Ability to understand and willingness to sign a written informed consent document.

Exclusion criteria

  • Diagnosis of germ cell tumor, small cell carcinoma or hematologic malignancy.
  • Metastases in the brain stem, midbrain, pons, medulla, or within 7 mm of the optic apparatus (optic nerves, chiasm and optic tracts).
  • Diagnosis of leptomeningeal disease.
  • Prior cranial radiotherapy within 90 days of trial enrollment or prior SRS at any time to any lesion to be treated on protocol
  • Chemotherapy (including oral agents and targeted agents) or immunotherapy given within 14 days of SRS. Hormonal therapy is permitted. For Her2+ breast cancer patients, anti-Her2 therapy cannot be given within 14 days of SRS. Patients who are scheduled to receive trastuzumab emtansine after SRS cannot be enrolled.
  • Contraindications to gadolinium contrast-enhanced MRI (eg, non-compatible pacemaker, eGFR<30, gadolinium allergy).

Treatment and study plan

Stereotactic radiosurgery

Procedure

The SRS dose will depend on the maximum diameter of the gross tumor volume (GTV)

Primary outcomes

  1. Progression free survival (PFS) rates estimated by the Kaplan-Meier method at 6 months

    Time frame: 6 months

    Progression free survival (PFS) rates will be estimated by the Kaplan-Meier method and the 0-mm and 2-mm groups will be compared via the log-rank statistic with a one-sided test of significance, using follow-up data up to 6 months.

Secondary outcomes

  1. Progression free survival (PFS) rates estimated by the Kaplan-Meier method

    Time frame: 2 years

    Progression free survival (PFS) rates will be estimated by the Kaplan-Meier method and the 0-mm, and 2-mm groups will be compared via the log-rank statistic with a one-sided test of significance, using follow-up data up to 6 months.

  2. Overall survival rates

    Time frame: 2 years

    Time from Stereotactic Radiosurgery (SRS) completion to death.

  3. Rates of radiation necrosis

    Time frame: 2 years

    To evaluate the superiority of frameless LINAC-based SRS using 0 mm margins compared to 2 mm margins in reducing rates of radiation necrosis.

  4. Rates of pseudoprogression

    Time frame: 2 years

    To evaluate the superiority of frameless LINAC-based SRS using 0 mm margins compared to 2 mm margins in reducing rates of radiation pseudoprogression.

  5. Local failure rates

    Time frame: 2 years

    Local failure and OS rates at 6 months, 1 year and 2 years will be estimated by the Kaplan-Meier method, comparing arms via the log-rank statistic.

  6. Rate of acute central nervous system (CNS) Common Terminology Criteria for Adverse Events (CTCAE) v4.0 grade 2 and higher toxicities

    Time frame: 90 days

    Any acute CTCAE v4.0 CNS Grade 2+ and Grade 3+ toxicities, within 90 days of SRS completion (toxicity must be specified).

  7. Rate of late central nervous system (CNS) Common Terminology Criteria for Adverse Events (CTCAE) v4.0 grade 2 and higher toxicities

    Time frame: 2 years

    To compare rates of late (greater than 90 days from SRS) CTCAE v4.0 CNS Grade 2+ and Grade 3+ toxicities.

  8. Rates of distant intracranial failure

    Time frame: 2 years

    The appearance of new non-target lesions ≥5 mm following completion of radiotherapy will be considered distant intracranial failure. If a non-target lesion <5 mm is found on a later scan to have increased to ≥ 5 mm, distant intracranial failure will be declared at the date of the earliest scan showing the new lesion.

  9. Rates of salvage therapy

    Time frame: 2 years

    Time to initiation of any combination of salvage Stereotactic Radiosurgery (SRS), Whole Brain Radiation Therapy WBRT, or neurosurgical resection for intracranial failure.

  10. Association between dose and risk of radionecrosis or pseudoprogression

    Time frame: 2 years

    To determine association between V10Gy and V12Gy all tissue, whole brain and normal brain parameters and risk of radionecrosis or pseudoprogression.

Study contacts

Contact information is provided by the study sponsor or research team.

Robyn Hseu

CONTACT

[email protected]

773-834-3198

Sponsors and collaborators

Lead sponsor

University of Chicago

Other

Registry information

Official study title

The Clinical Relevance of Margins in Frameless Stereotactic Radiosurgery for Intact Brain Metastases: a Randomized Trial of 0 vs 2 mm Margins

Important dates

Study start
2023
Primary completion
2028
Study completion
2028
First posted
Apr 21, 2016
Registry last updated
Dec 29, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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