MR-Linac Guided Adaptive FSRT for Brain Metastases From Non-small Cell Lung Cancer

NCT04946019 | Completed Phase 2

• 1 other identifier: GASTO-1075
• Study Type: interventional
• Target: 55
• Locations: 1 country
• Sites: 1

Brief Summary

This Phase II study is to determine the efficacy and safety of MR-Linac Guided Adaptive fractionated stereotactic radiotherapy (FSRT) in patients with brain metastases in non-small cell lung cancer.

Conditions

Non-small Cell Lung Cancer

Keywords

Non-small cell lung cancer; MR-Linac; Fractionated stereotactic radiation therapy; Brain metastase

Outcome Measures

Primary Outcomes (1)

• 1-year intracranial progression-free survival

  1 year

Secondary Outcomes (8)

• Objective response rate

  2 months

• 1-year progression-free survival

  1 year

• 1-year overall survival

  1 year

• Rate of participants with perilesional edema of brain metastases evaluated byT2-weighted MRI

  1 year

• Quality of life evaluated by EORTC quality of life questionnaire

  1 year

Study Arms (1)

MR-Linac Guided Adaptive FSRT

EXPERIMENTAL

Patients will receive FSRT (30Gy in 5 fractions) on the MR-Linac treatment machine.

Combination Product: Unity-based MR-Linac guided FSRT

Interventions

Unity-based MR-Linac guided FSRT COMBINATION_PRODUCT

The FSRT was delivered using the Unity-based MR-Linac treatment machine, with a total dose of 30Gy in 5 fractions.

MR-Linac Guided Adaptive FSRT

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Aged 18-75 years
• Histologically or cytologically confirmed non-small cell lung cancer
• metastases on contrast-enhanced MRI
• Radiotherapy for extracranial lesions is permitted
• Tyrosine kinase inhibitors (TKI) are permitted in patients with progression of intracranial metastases during previous TKI therapy
• Patients have measurable or evaluable lesions based on the Response Evaluation Criteria in Solid Tumors (RECIST) criteria
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1
• Normal function of organs and bone marrow within 14 days: Total bilirubin 1.5 times or less the upper limits of normal (ULN); AST and ALT 1.5 times or less the ULN; absolute neutrophil count≥ 500 cells/mm3; creatinine clearance rate(CCR) ≥45 mL/min; Platelet count≥50,000 cells/mm3; international normalized ratio(INR) ≤1.5#Prothrombin Time (PT)≤ 1.5 × ULN
• Informed-consent

You may not qualify if:

• Small cell carcinoma of lung
• Intracranial metastases needed surgical decompression
• Patients with contraindications for MRI
• Previous radiotherapy or excision for intracranial metastases
• The tumor has completely approached, encircled, or invaded the intravascular space of the great vessels (e.g., the pulmonary artery or the superior vena cava)
• A cavity over 2cm in diameter of primary tumor or metastasis
• Bleeding tendency or coagulation disorder
• Hemoptysis (1/2 teaspoon blood/day) happened within 1 month
• The use of full-dose anticoagulation within the past 1 month
• Severe vascular disease occurred within 6 months
• Gastrointestinal fistula, perforation or abdominal abscess occurred within 6 months
• Hypertensive crisis, hypertensive encephalopathy, symptomatic heart failure (New York class II or above), active cerebrovascular disease or cardiovascular disease occurred within 6 months
• Uncontrolled hypertension (systolic \> 150mmHg and/or diastolic \> 100mmHg)
• Major surgery within 28 days or minor surgery or needle biopsy within 48 hours
• Urine protein 3-4+, or 24h urine protein quantitative \>1g

Sponsors & Collaborators

• Sun Yat-sen University: lead

Study Sites (1)

Hui Liu

Guangzhou, Guangdong, 510060, China

Location

Related Publications (16)

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  PMID: 24048959 BACKGROUND

• Yamamoto M, Serizawa T, Shuto T, Akabane A, Higuchi Y, Kawagishi J, Yamanaka K, Sato Y, Jokura H, Yomo S, Nagano O, Kenai H, Moriki A, Suzuki S, Kida Y, Iwai Y, Hayashi M, Onishi H, Gondo M, Sato M, Akimitsu T, Kubo K, Kikuchi Y, Shibasaki T, Goto T, Takanashi M, Mori Y, Takakura K, Saeki N, Kunieda E, Aoyama H, Momoshima S, Tsuchiya K. Stereotactic radiosurgery for patients with multiple brain metastases (JLGK0901): a multi-institutional prospective observational study. Lancet Oncol. 2014 Apr;15(4):387-95. doi: 10.1016/S1470-2045(14)70061-0. Epub 2014 Mar 10.

  PMID: 24621620 BACKGROUND

• Rades D, Janssen S, Dziggel L, Blanck O, Bajrovic A, Veninga T, Schild SE. A matched-pair study comparing whole-brain irradiation alone to radiosurgery or fractionated stereotactic radiotherapy alone in patients irradiated for up to three brain metastases. BMC Cancer. 2017 Jan 6;17(1):30. doi: 10.1186/s12885-016-2989-3.

  PMID: 28061768 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

• Barrett OC, McDonald AM, Thompson JW, Bredel M, McGwin G, Riley KO, Fiveash JB. Distant brain recurrence in patients with five or more newly diagnosed brain metastases treated with focal stereotactic radiotherapy alone. J Radiosurg SBRT. 2017;4(4):255-263.

  PMID: 28626600 BACKGROUND

• Lagendijk JJ, Raaymakers BW, Van den Berg CA, Moerland MA, Philippens ME, van Vulpen M. MR guidance in radiotherapy. Phys Med Biol. 2014 Nov 7;59(21):R349-69. doi: 10.1088/0031-9155/59/21/R349. Epub 2014 Oct 16. No abstract available.

  PMID: 25322150 BACKGROUND

• MacManus M, Everitt S, Schimek-Jasch T, Li XA, Nestle U, Kong FS. Anatomic, functional and molecular imaging in lung cancer precision radiation therapy: treatment response assessment and radiation therapy personalization. Transl Lung Cancer Res. 2017 Dec;6(6):670-688. doi: 10.21037/tlcr.2017.09.05.

  PMID: 29218270 BACKGROUND

• Khoo VS, Joon DL. New developments in MRI for target volume delineation in radiotherapy. Br J Radiol. 2006 Sep;79 Spec No 1:S2-15. doi: 10.1259/bjr/41321492.

  PMID: 16980682 BACKGROUND

• Raaymakers BW, Lagendijk JJ, Overweg J, Kok JG, Raaijmakers AJ, Kerkhof EM, van der Put RW, Meijsing I, Crijns SP, Benedosso F, van Vulpen M, de Graaff CH, Allen J, Brown KJ. Integrating a 1.5 T MRI scanner with a 6 MV accelerator: proof of concept. Phys Med Biol. 2009 Jun 21;54(12):N229-37. doi: 10.1088/0031-9155/54/12/N01. Epub 2009 May 19.

  PMID: 19451689 BACKGROUND

• Stemkens B, Tijssen RH, de Senneville BD, Lagendijk JJ, van den Berg CA. Image-driven, model-based 3D abdominal motion estimation for MR-guided radiotherapy. Phys Med Biol. 2016 Jul 21;61(14):5335-55. doi: 10.1088/0031-9155/61/14/5335. Epub 2016 Jun 30.

  PMID: 27362636 BACKGROUND

• Dietz B, Yip E, Yun J, Fallone BG, Wachowicz K. Real-time dynamic MR image reconstruction using compressed sensing and principal component analysis (CS-PCA): Demonstration in lung tumor tracking. Med Phys. 2017 Aug;44(8):3978-3989. doi: 10.1002/mp.12354. Epub 2017 Jun 28.

  PMID: 28543069 BACKGROUND

• Glitzner M, Crijns SP, de Senneville BD, Kontaxis C, Prins FM, Lagendijk JJ, Raaymakers BW. On-line MR imaging for dose validation of abdominal radiotherapy. Phys Med Biol. 2015 Nov 21;60(22):8869-83. doi: 10.1088/0031-9155/60/22/8869. Epub 2015 Nov 4.

  PMID: 26531846 BACKGROUND

• Kontaxis C, Bol GH, Stemkens B, Glitzner M, Prins FM, Kerkmeijer LGW, Lagendijk JJW, Raaymakers BW. Towards fast online intrafraction replanning for free-breathing stereotactic body radiation therapy with the MR-linac. Phys Med Biol. 2017 Aug 21;62(18):7233-7248. doi: 10.1088/1361-6560/aa82ae.

  PMID: 28749375 BACKGROUND

• Raaymakers BW, Jurgenliemk-Schulz IM, Bol GH, Glitzner M, Kotte ANTJ, van Asselen B, de Boer JCJ, Bluemink JJ, Hackett SL, Moerland MA, Woodings SJ, Wolthaus JWH, van Zijp HM, Philippens MEP, Tijssen R, Kok JGM, de Groot-van Breugel EN, Kiekebosch I, Meijers LTC, Nomden CN, Sikkes GG, Doornaert PAH, Eppinga WSC, Kasperts N, Kerkmeijer LGW, Tersteeg JHA, Brown KJ, Pais B, Woodhead P, Lagendijk JJW. First patients treated with a 1.5 T MRI-Linac: clinical proof of concept of a high-precision, high-field MRI guided radiotherapy treatment. Phys Med Biol. 2017 Nov 14;62(23):L41-L50. doi: 10.1088/1361-6560/aa9517.

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• 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

• Zheng S, Ding S, Liu B, Xiong Y, Zhou R, Zhang P, Liu F, Liu Y, Chen M, Situ Y, Wang M, Huang X, Yin S, Fang W, Mou Y, Qiu B, Wang D, Liu H. Efficacy and safety of online adaptive magnetic resonance-guided fractionated stereotactic radiotherapy for brain metastases in non-small cell lung cancer (GASTO-1075): a single-arm, phase 2 trial. EClinicalMedicine. 2025 Apr 9;82:103189. doi: 10.1016/j.eclinm.2025.103189. eCollection 2025 Apr.

  PMID: 40247887 DERIVED

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Brain Neoplasms

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Central Nervous System Neoplasms; Nervous System Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Study Officials

• Hui Liu, Ph.D

  Sun Yat-sen University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: June 25, 2021
• First Posted: June 30, 2021
• Study Start: June 1, 2021
• Primary Completion: July 17, 2024
• Study Completion: July 17, 2024
• Last Updated: December 12, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)