Clinical trial NCT03414944: Elective Simultaneous Modulated Accelerated Brain Radiation Therapy for NSCLCs With Limited Brain Metastases
Official title: Elective Simultaneous Modulated Accelerated Brain Radiation Therapy for NSCLCs With Limited Brain Metastases,A Phase I,One-arm Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Brain Metastases
Keywords: Non-small cell lung cancer
Brain metastases
SIB
hippocampus avoidance
inner ear avoidance
Lead sponsor: Shandong Cancer Hospital and Institute
Sponsor class: OTHER
Collaborators: name: Shandong Provincial Hospital
name: Qilu Hospital of Shandong University
name: The Affiliated Hospital of Xuzhou Medical University
First posted: 2018-01-30
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Brain metastases are the most common intracranial tumors in adults. Whole-brain radiation therapy (WBI) increases the median survival of patients with brain metastases up to 3-6 months, but WBI can lead to the decline of cognition and quality of life, with short local control time. The use of SIB(simultaneous integrated boost) technology can increase the local control rate. Hippocampus avoidance can effectively reduce the cognitive impairment caused by WBI.This study was designed to evaluate the safety and efficacy of selective brain radiotherapy (EBI)(based on SIB and hippocampus, inner ear avoidance )in NSCLCs with limited brain metastases.

Detailed description: In this prospective phase 1 study evaluating the safety and efficacy of selective brain radiotherapy in NSCLCs with limited brain metastases, patients will received selective brain radiotherapy based on SIB and hippocampus, inner ear avoidance.

Prescription dose: Gross tumor (PGTV) 40-50 Gy/10 fractions/2 weeks + EBI (PCTV) 30 Gy/10 fractions/2 weeks.

OARs dose limits: Hippocampus D100%≤10Gy, Dmax≤17Gy,Inner ear: Dmean ≤15Gy. All patients were observed and recorded daily for acute radiation impairment during radiotherapy. Follow-up every 2 months will be performed after radiotherapy.

The primary endpoint:Acute and chronic radiation response, QOL in patients, vestibular function,neurocognitive function based on mini-mental state examination(MMSE) questionnaires, hearing.

The secondary endpoint included:objective response rate (ORR);intracranial progression-free survival (iPFS); OS (defined as the time from study beginning to death from any cause).

Eligibility criteria: Inclusion Criteria:

histologically or cytologically confirmed NSCLC with MRI confirmed new brain metastases a life expectancy of at least 3 months; adequate organ function according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.0.

Exclusion Criteria:

radiologically or pathologically confirmed metastases in the spinal cord or meninges obvious hernia formation risk previously received brain surgery or radiotherapy a history or presence of poorly controlled systemic diseases pregnant patients

Primary outcomes:
measure: AE
timeFrame: up to 12 months
Secondary outcomes:
measure: iPFS
timeFrame: From date of treatment begining until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 12 months
Other outcomes:
Locations:
city: Jin'an
country: China
facility: Shandong Cancer Hospital
state: Shandong
Study officials:
affiliation: Shandong cancer hospital and constitute
name: Yuan Shuanghu, doctor
role: STUDY_CHAIR
References:
citation: Aoyama H, Shirato H, Tago M, Nakagawa K, Toyoda T, Hatano K, Kenjyo M, Oya N, Hirota S, Shioura H, Kunieda E, Inomata T, Hayakawa K, Katoh N, Kobashi G. Stereotactic radiosurgery plus whole-brain radiation therapy vs stereotactic radiosurgery alone for treatment of brain metastases: a randomized controlled trial. JAMA. 2006 Jun 7;295(21):2483-91. doi: 10.1001/jama.295.21.2483.
citation: 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.
citation: 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.
citation: Meyers CA, Brown PD. Role and relevance of neurocognitive assessment in clinical trials of patients with CNS tumors. J Clin Oncol. 2006 Mar 10;24(8):1305-9. doi: 10.1200/JCO.2005.04.6086.
citation: 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.
citation: Miller JA, Kotecha R, Suh JH. Comparative effectiveness of stereotactic radiosurgery versus whole-brain radiation therapy for patients with brain metastases from breast or non-small cell lung cancer. Cancer. 2016 Oct 15;122(20):3243-3244. doi: 10.1002/cncr.30188. Epub 2016 Jul 8. No abstract available.
citation: Ozdemir Y, Yildirim BA, Topkan E. Whole brain radiotherapy in management of non-small-cell lung carcinoma associated leptomeningeal carcinomatosis: evaluation of prognostic factors. J Neurooncol. 2016 Sep;129(2):329-35. doi: 10.1007/s11060-016-2179-9. Epub 2016 Jun 15.
citation: Mekhail T, Sombeck M, Sollaccio R. Adjuvant whole-brain radiotherapy versus observation after radiosurgery or surgical resection of one to three cerebral metastases: results of the EORTC 22952-26001 study. Curr Oncol Rep. 2011 Aug;13(4):255-8. doi: 10.1007/s11912-011-0180-1. No abstract available.
citation: Jiang A, Sun W, Zhao F, Wu Z, Shang D, Yu Q, Wang S, Zhu J, Yang F, Yuan S. Dosimetric evaluation of four whole brain radiation therapy approaches with hippocampus and inner ear avoidance and simultaneous integrated boost for limited brain metastases. Radiat Oncol. 2019 Mar 15;14(1):46. doi: 10.1186/s13014-019-1255-7.