NanoTherm In Adjuvant Therapy of Glioblastoma Multiforme

Summary

Glioblastoma multiforme (GBM), the most common and malignant primary brain tumor in adults is classified as a World Health Organisation (WHO) grade 4. Surgical removal of the tumor is the primary method of treatment. Unfortunately, because GBM is a disease of the entire brain, total resection is not possible. Therefore, the use of radiotherapy and/or chemotherapy is considered as Stupp protocol. Patients with recurrent GBM will be included in the ANCHIALE study. The goal of the trial is to evaluate the efficacy and tolerance of using the NanoTherm therapy system in recurrent GBM. The main questions it aims to answer are: 1. how NanoTherm therapy influences overall survival, and progression free survival; 2. what is the tolerance of NanoTherm therapy in terms of side effects (allergies, intracranial bleeding, infections, brain edema, increased intracranial pressure) and quality of life. Participants will undergo: * initial visit, considering the inclusion/exclusion criteria, neurological examination, and surveys regarding daily functioning and quality of life; * standard neurosurgical operation aimed, if possible, complete removal of the recurrent GBM and administration of NanoTherm ASI - a sterile suspension of iron oxide nanoparticles. A catheter will be implanted allowing for measurement of temperature during the first activation in the magnetic field; * between the 6th and 10th day after tumor resection, a standard computerized tomography (CT) scan of the head will be performed for routine postoperative evaluation; * after the first activation (10th day), the catheter will be removed; * subsequently, for 6 times, the patient will be subjected to the variable magnetic field of the NanoActivator® to induce hyperthermia - activations will be conducted on the 10th, 14th, 17th, 21st, 24th, and 28th day; * for up to 2 years post-procedure, a CT scan with an evaluation of treatment efficacy will be performed; * during follow-up visits for up to 2 years after the surgical procedure, a neurological examination, assessment of adverse symptoms, number of hospitalizations, number of medical visits, clinimetric assessment regarding quality of life, neurological deficit and degree of disability will be conducted. Researchers will compare NanoTherm group with patients undergoing Stupp protocol treatment for the abovementioned effects.

Timeline

Start

2024-01-01

Primary completion

2027-02-01

Completion

2027-09-01

Publications

• Background Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, Belanger K, Brandes AA, Marosi C, Bogdahn U, Curschmann J, Janzer RC, Ludwin SK, Gorlia T, Allgeier A, Lacombe D, Cairncross JG, Eisenhauer E, Mirimanoff RO; European Organisation for Research and Treatment of Cancer Brain Tumor and Radiotherapy Groups; National Cancer Institute of Canada Clinical Trials Group. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 2005 Mar 10;352(10):987-96. doi: 10.1056/NEJMoa043330.
• Background Barker CA, Chang M, Chou JF, Zhang Z, Beal K, Gutin PH, Iwamoto FM. Radiotherapy and concomitant temozolomide may improve survival of elderly patients with glioblastoma. J Neurooncol. 2012 Sep;109(2):391-7. doi: 10.1007/s11060-012-0906-4. Epub 2012 Jun 12.
• Background Gupta T, Sarin R. Poor-prognosis high-grade gliomas: evolving an evidence-based standard of care. Lancet Oncol. 2002 Sep;3(9):557-64. doi: 10.1016/s1470-2045(02)00853-7.
• Background Sun J, Guo M, Pang H, Qi J, Zhang J, Ge Y. Treatment of malignant glioma using hyperthermia. Neural Regen Res. 2013 Oct 15;8(29):2775-82. doi: 10.3969/j.issn.1673-5374.2013.29.009.
• Background Mahmoudi K, Bouras A, Bozec D, Ivkov R, Hadjipanayis C. Magnetic hyperthermia therapy for the treatment of glioblastoma: a review of the therapy's history, efficacy and application in humans. Int J Hyperthermia. 2018 Dec;34(8):1316-1328. doi: 10.1080/02656736.2018.1430867. Epub 2018 Feb 6.
• Background Maier-Hauff K, Ulrich F, Nestler D, Niehoff H, Wust P, Thiesen B, Orawa H, Budach V, Jordan A. Efficacy and safety of intratumoral thermotherapy using magnetic iron-oxide nanoparticles combined with external beam radiotherapy on patients with recurrent glioblastoma multiforme. J Neurooncol. 2011 Jun;103(2):317-24. doi: 10.1007/s11060-010-0389-0. Epub 2010 Sep 16.
• Background Pinel S, Thomas N, Boura C, Barberi-Heyob M. Approaches to physical stimulation of metallic nanoparticles for glioblastoma treatment. Adv Drug Deliv Rev. 2019 Jan 1;138:344-357. doi: 10.1016/j.addr.2018.10.013. Epub 2018 Nov 7.
• Background Boroon MP, Ayani MB, Bazaz SR. Estimation of the optimum number and location of nanoparticle injections and the specific loss power for ideal hyperthermia. J Therm Biol. 2018 Feb;72:127-136. doi: 10.1016/j.jtherbio.2018.01.010. Epub 2018 Jan 31.
• Background Grauer O, Jaber M, Hess K, Weckesser M, Schwindt W, Maring S, Wolfer J, Stummer W. Combined intracavitary thermotherapy with iron oxide nanoparticles and radiotherapy as local treatment modality in recurrent glioblastoma patients. J Neurooncol. 2019 Jan;141(1):83-94. doi: 10.1007/s11060-018-03005-x. Epub 2018 Dec 1.
• Background Huang H, Yu K, Mohammadi A, Karanthanasis E, Godley A, Yu JS. It's Getting Hot in Here: Targeting Cancer Stem-like Cells with Hyperthermia. J Stem Cell Transplant Biol. 2017;2(2):113. Epub 2017 Dec 29.
• Background Curran WJ Jr, Scott CB, Horton J, Nelson JS, Weinstein AS, Fischbach AJ, Chang CH, Rotman M, Asbell SO, Krisch RE, et al. Recursive partitioning analysis of prognostic factors in three Radiation Therapy Oncology Group malignant glioma trials. J Natl Cancer Inst. 1993 May 5;85(9):704-10. doi: 10.1093/jnci/85.9.704.
• Background Dong X, Noorbakhsh A, Hirshman BR, Zhou T, Tang JA, Chang DC, Carter BS, Chen CC. Survival trends of grade I, II, and III astrocytoma patients and associated clinical practice patterns between 1999 and 2010: A SEER-based analysis. Neurooncol Pract. 2016 Mar;3(1):29-38. doi: 10.1093/nop/npv016. Epub 2015 Jul 1.
• Background Gupta R, Sharma D. Evolution of Magnetic Hyperthermia for Glioblastoma Multiforme Therapy. ACS Chem Neurosci. 2019 Mar 20;10(3):1157-1172. doi: 10.1021/acschemneuro.8b00652. Epub 2019 Feb 19.
• Background Hegi ME, Liu L, Herman JG, Stupp R, Wick W, Weller M, Mehta MP, Gilbert MR. Correlation of O6-methylguanine methyltransferase (MGMT) promoter methylation with clinical outcomes in glioblastoma and clinical strategies to modulate MGMT activity. J Clin Oncol. 2008 Sep 1;26(25):4189-99. doi: 10.1200/JCO.2007.11.5964.
• Background Laperriere N, Zuraw L, Cairncross G; Cancer Care Ontario Practice Guidelines Initiative Neuro-Oncology Disease Site Group. Radiotherapy for newly diagnosed malignant glioma in adults: a systematic review. Radiother Oncol. 2002 Sep;64(3):259-73. doi: 10.1016/s0167-8140(02)00078-6.
• Background Nwokedi EC, DiBiase SJ, Jabbour S, Herman J, Amin P, Chin LS. Gamma knife stereotactic radiosurgery for patients with glioblastoma multiforme. Neurosurgery. 2002 Jan;50(1):41-6; discussion 46-7. doi: 10.1097/00006123-200201000-00009.
• Background Paszat L, Laperriere N, Groome P, Schulze K, Mackillop W, Holowaty E. A population-based study of glioblastoma multiforme. Int J Radiat Oncol Biol Phys. 2001 Sep 1;51(1):100-7. doi: 10.1016/s0360-3016(01)01572-3.
• Background Stupp R, Taillibert S, Kanner A, Read W, Steinberg D, Lhermitte B, Toms S, Idbaih A, Ahluwalia MS, Fink K, Di Meco F, Lieberman F, Zhu JJ, Stragliotto G, Tran D, Brem S, Hottinger A, Kirson ED, Lavy-Shahaf G, Weinberg U, Kim CY, Paek SH, Nicholas G, Bruna J, Hirte H, Weller M, Palti Y, Hegi ME, Ram Z. Effect of Tumor-Treating Fields Plus Maintenance Temozolomide vs Maintenance Temozolomide Alone on Survival in Patients With Glioblastoma: A Randomized Clinical Trial. JAMA. 2017 Dec 19;318(23):2306-2316. doi: 10.1001/jama.2017.18718.

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