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

NCT01218542 | Completed Results DMC

• 2 other identifiers: IRB00045035WCI1784-10
• Study Type: interventional
• Target: 22
• 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. 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.

Conditions

Neoplasm Metastasis

Keywords

Secondary brain malignancies; RapidArc; Volumetric modulated arc therapy

Outcome Measures

Primary Outcomes (1)

• Percent of Participants With Locoregional Control of Treating Brain Metastasis Patients

  The cumulative incidences of recurrence locally and in the whole brain were reported at the patient level.

  Locoregional control at 1 year

Secondary Outcomes (4)

• Brain Progression-free Survival

  11 months median follow up period.

• Overall Survival

  11 months median follow up period.

• Neurocognitive Effects

  11 months median follow up period.

• Quality of Life as Measured by the FACT-Br Subscales

  11 month median follow up

Study Arms (1)

Volumetric modulated arc therapy

EXPERIMENTAL

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.

Radiation: Volumetric modulated arc therapy

Interventions

Volumetric modulated arc therapy RADIATION

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

Volumetric modulated arc therapy

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.
• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• Emory University: lead

Study Sites (2)

Emory University Hospital Midtown

Atlanta, Georgia, 30308, United States

Location

Emory University/Winship Cancer Institute

Atlanta, Georgia, 30322, United States

Location

Related Publications (10)

• 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.

  PMID: 7237407 BACKGROUND

• 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.

  PMID: 9677016 BACKGROUND

• 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.

  PMID: 13172684 BACKGROUND

• 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.

  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

• 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

• 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.

  PMID: 19577856 BACKGROUND

• 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.

  PMID: 17278893 BACKGROUND

• 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.

  PMID: 31970594 RESULT

MeSH Terms

Conditions

Neoplasm Metastasis

Interventions

Radiotherapy, Intensity-Modulated

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Radiotherapy, Conformal; Radiotherapy, Computer-Assisted; Radiotherapy; Therapeutics

Results Point of Contact

• Title: Dr. Hui-Kuo Shu
• Organization: Emory University

hgshu@emory.edu

404-778-2161

Study Officials

• Hui-Kuo Shu, MD, PhD

  Emory University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, Principal Investigator

Study Record Dates

• First Submitted: September 30, 2010
• First Posted: October 11, 2010
• Study Start: September 22, 2010
• Primary Completion: June 3, 2020
• Study Completion: June 3, 2020
• Last Updated: June 29, 2021
• Results First Posted: June 29, 2021

Record last verified: 2021-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)