Whole Brain Radiation Therapy With Boost to Metastatic Tumor Volume Using RapidArc

NCT ID: NCT01218542

Last Updated: 2021-06-29

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

22 participants

Study Classification

INTERVENTIONAL

Study Start Date

2010-09-22

Study Completion Date

2020-06-03

Brief Summary

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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. The most widely used treatment for patients with multiple brain metastases is whole brain radiation therapy (WBRT). The use of WBRT after resection or stereotactic radiosurgery (SRS) has been proven to be effective in terms of improving local control of brain metastases.

RapidArc (RA) (Varian Medical Systems, Palo Alto, CA) is a new method of delivering radiation that uses "arcs" to deliver highly conformal intensity modulated three dimensional dose distributions. The purpose of this investigation is to evaluate an alternative strategy for giving WBRT with highly focal boost to gross visible lesions in patients with brain metastasis.

Given the limitations of the SRS boost technique, the purpose of our investigation is to evaluate an alternative strategy for giving WBRT with highly focal boost to gross visible lesions in patients with brain metastasis. In this study, we plan to assess the tolerability of using volumetric modulated arc therapy (RapidArc) on patients with brain metastasis to simultaneously treat the entire brain with a concomitant focal boost to grossly identified lesions on MRI scan to try to improve local control and reduce neurocognitive toxicities.

This previous version of this study was a phase I dose escalation trial giving 25 Gy in 10 fractions to the whole brain with simultaneous infield boost (SIB) to a total of 45 Gy in 10 fractions to gross brain metastatic disease. Prior to this, patients were enrolled onto one of two cohorts with whole brain dose of 30 Gy in 10 fractions with SIB to total of 45 Gy in 10 fractions to gross brain metastatic disease or whole brain dose of 37.5 Gy in 15 fractions with SIB to total of 52.5 Gy in 15 fractions to gross brain metastatic disease. A total of 12 patients have been previously enrolled on this trial. No patients have experienced a dose limiting toxicity (grade 3 or above) at least possibly due to study therapy. Also, no patients experienced local brain failure/progression at a site of treated metastatic brain disease. Based on this, we no longer feel that dose escalation to the gross brain disease is warranted and would proceed with a single arm pilot study treating patients with 25 Gy in 10 fractions to the whole brain with simultaneous infield boost (SIB) to a total of 45 Gy in 10 fractions to gross brain metastatic disease.

Detailed Description

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Conditions

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Neoplasm Metastasis

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Volumetric modulated arc therapy

Single arm pilot study treating patients with 25 Gy in 10 fractions to the whole brain with simultaneous infield boost (SIB) to a total of 45 Gy in 10 fractions to gross brain metastatic disease.

Group Type EXPERIMENTAL

Volumetric modulated arc therapy

Intervention Type RADIATION

Using volumetric modulated arc therapy to give simultaneous infield boost to gross metastatic brain lesions during whole brain radiation therapy.

Interventions

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Volumetric modulated arc therapy

Using volumetric modulated arc therapy to give simultaneous infield boost to gross metastatic brain lesions during whole brain radiation therapy.

Intervention Type RADIATION

Eligibility Criteria

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Inclusion Criteria

* Pathologic proven diagnosis of solid tumor malignancy.
* Age ≥ 18.
* KPS ≥ 70.
* Mini Mental Status Exam (MMSE) ≥ 18 prior to study entry.
* RPA class I (KPS ≥ 70, primary cancer controlled, age \< 65, metastases in brain only) or class II (lack of one or more of class I criteria).
* One to ten brain metastatic lesions.

Exclusion Criteria

* Previous whole brain radiation therapy.
* Previous radiosurgery to any currently progressive gross metastatic disease.
* Previous radiosurgery to any intracranial site within the prior 6 weeks.
* Recursive partitioning analysis (RPA) class III (KPS \< 70).
* Radiosensitive (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).
* Evidence of leptomeningeal disease by MRI and/or cerebrospinal fluid (CSF) cytology.
* Current pregnancy.
* No metastases to brain stem, midbrain, pons, or medulla or within 7 mm of the optic apparatus (optic nerves and chiasm).
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Emory University

OTHER

Sponsor Role lead

Responsible Party

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Hui-Kuo Shu, MD, PhD

MD, Principal Investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Hui-Kuo Shu, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Emory University

Locations

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Emory University Hospital Midtown

Atlanta, Georgia, United States

Site Status

Emory University/Winship Cancer Institute

Atlanta, Georgia, United States

Site Status

Countries

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United States

References

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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. doi: 10.1002/1097-0142(19810715)48:23.0.co;2-8.

Reference Type BACKGROUND
PMID: 7237407 (View on PubMed)

Sundstrom 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. doi: 10.3109/07853899809005858.

Reference Type BACKGROUND
PMID: 9677016 (View on PubMed)

CHAO JH, PHILLIPS R, NICKSON JJ. Roentgen-ray therapy of cerebral metastases. Cancer. 1954 Jul;7(4):682-9. doi: 10.1002/1097-0142(195407)7:43.0.co;2-s. No abstract available.

Reference Type BACKGROUND
PMID: 13172684 (View on PubMed)

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. doi: 10.1016/s0360-3016(96)00619-0.

Reference Type BACKGROUND
PMID: 9128946 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 12680791 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 8625178 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 15158627 (View on PubMed)

Lagerwaard FJ, van der Hoorn EA, Verbakel WF, Haasbeek CJ, Slotman BJ, Senan S. Whole-brain radiotherapy with simultaneous integrated boost to multiple brain metastases using volumetric modulated arc therapy. Int J Radiat Oncol Biol Phys. 2009 Sep 1;75(1):253-9. doi: 10.1016/j.ijrobp.2009.03.029. Epub 2009 Jul 4.

Reference Type BACKGROUND
PMID: 19577856 (View on PubMed)

Bauman G, Yartsev S, Fisher B, Kron T, Laperriere N, Heydarian M, VanDyk J. Simultaneous infield boost with helical tomotherapy for patients with 1 to 3 brain metastases. Am J Clin Oncol. 2007 Feb;30(1):38-44. doi: 10.1097/01.coc.0000245473.41035.c4.

Reference Type BACKGROUND
PMID: 17278893 (View on PubMed)

Zhong J, Waldman AD, Kandula S, Eaton BR, Prabhu RS, Huff SB, Shu HG. Outcomes of whole-brain radiation with simultaneous in-field boost (SIB) for the treatment of brain metastases. J Neurooncol. 2020 Mar;147(1):117-123. doi: 10.1007/s11060-020-03405-y. Epub 2020 Jan 22.

Reference Type RESULT
PMID: 31970594 (View on PubMed)

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

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WCI1784-10

Identifier Type: OTHER

Identifier Source: secondary_id

IRB00045035

Identifier Type: -

Identifier Source: org_study_id

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