NanoTherm In Adjuvant Therapy of Glioblastoma Multiforme

NCT06271421 | Recruiting

• 1 other identifier: 01/24
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief 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:

• 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.

Conditions

Glioblastoma Multiforme

Keywords

glioblastoma; adjuvant therapy; hyperthermia; NanoTherm; GBM

Outcome Measures

Primary Outcomes (2)

• Survival following the surgery [units months 1-24]

  overall survival

  2 years following surgery

• Progression free survival [units months 1-24]

  Progression Free Survival

  2 years after surgery

Secondary Outcomes (5)

• Response Assessment in Neuro-oncology [1 - complete response; 4 -progressive disease]

  2 years after surgery

• EuroQuality of Life 5-dimensions-5 levels scale (EQ-5D-5L) [arbitraty units 0- worst ; 100 - best]

  2 years after surgery

• Neurologic Assessment in Neuro-Oncology (NanoScale 2) [0-best; 23-worst]

  2 years after surgery

• modified Rankin scale [0-best; 6-worst]

  2 years after surgery

• Barthel index [range 0-100; 0-best, 100-worst]

  2 years after surgery

Study Arms (2)

NanoTherm arm (group A)

ACTIVE COMPARATOR

Recurrent glioblastoma multiforme patients treated with NanoTherm therapy.

Device: NanoTherm therapy; Procedure: Glioma Resection

Stupp protocol (group B)

PLACEBO COMPARATOR

Glioblastoma multiforme patients treated according to Stupp protocol including surgery, chemotherapy and radiotherapy.

Procedure: Glioma Resection; Radiation: radiotherapy according to Stupp protocol; Drug: chemotherapy according to Stupp protocol

Interventions

NanoTherm therapy DEVICE

Cyclic hyperthermia in patients with recurrent glioblastoma multiforme, who underwent implantation of iron oxide nanoparticles.

Also known as: Cyclic hyperthermia

NanoTherm arm (group A)

Glioma Resection PROCEDURE

Removal of brain tumor - gross total ressection

Also known as: Surgical removal of Glioma tumor

NanoTherm arm (group A); Stupp protocol (group B)

radiotherapy according to Stupp protocol RADIATION

The total dose according to the Stupp protocol is 60 Gy and is administered in fractions of 2 Gy per day for 5 days (Monday to Friday) for 6 weeks.

Stupp protocol (group B)

chemotherapy according to Stupp protocol DRUG

Temozolomide is used during radiotherapy: 75 mg/m2 of body surface area per day for 7 days a week. After the completion of radiotherapy, temozolomide is used as adjuvant therapy - 6 cycles of 150-200 mg/m2 of body surface area for 5 days every 28 days.

Also known as: temozolomide

Stupp protocol (group B)

Eligibility Criteria

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

You may qualify if:

• Recurrence of glioblastoma multiforme.
• Age \> 18 years.
• Informed written consent to participate in the study.
• Karnofsky performance score ≥ 60.
• Expected survival time \> 6 months.
• Failure of standard treatment according to the Stupp protocol.
• Cardio-respiratory fitness - allowing to stay for 60 minutes in a lying position in the field activator.

You may not qualify if:

• Pregnant or breastfeeding women.
• More than 3 foci of glioblastoma multiforme.
• Tumor invasion of eloquent or motor areas.
• Subependymal contrast enhancement in the adjacent brain ventricles.
• Concurrent immunotherapy for glioblastoma.
• Metal implants within ≤ 40 cm of the planned exposure field: metal dental fillings/restorations, cervical spine implants, metal elements left after previous craniotomies, metal elements used in osteosynthesis after orthopedically treated injuries, vascular ports with metal components.
• Electronic implants: pacemakers, cardioverter defibrillators, cochlear implants, deep brain stimulation (DBS) electrodes.
• Allergy/hypersensitivity to aminosilanes, iron oxide, acetic acid.
• Planned or current treatment with electromagnetic field in the Optune®TTF system.
• Claustrophobia not amenable to control.
• Painful conditions, musculoskeletal system diseases that prevent staying in a lying position.

Sponsors & Collaborators

• Poznan University of Medical Sciences: lead
• MagForce USA: collaborator

Study Sites (1)

University Hospital

Poznan, 60-355, Poland

RECRUITING

Related Publications (18)

• 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.

  PMID: 15758009 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.

  PMID: 22688802 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.

  PMID: 12217793 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.

  PMID: 25206588 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.

  PMID: 29353516 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.

  PMID: 20845061 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.

  PMID: 30414495 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.

  PMID: 29496005 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.

  PMID: 30506500 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.

  PMID: 30542674 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.

  PMID: 8478956 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.

  PMID: 31579519 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.

  PMID: 30715851 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.

  PMID: 18757334 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.

  PMID: 12242114 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.

  PMID: 11844233 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.

  PMID: 11516858 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.

  PMID: 29260225 BACKGROUND

Related Links

• IQWiG, Institut für Qualität und Wirtschaftlichkeit im Gesundheitswesen, 2019.
• Tadashi Osawa et al. Elderly patients aged over 75 years with glioblastoma: Preoperative status and surgical strategies.

MeSH Terms

Conditions

Glioblastoma; Hyperthermia

Interventions

Temozolomide

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Body Temperature Changes; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Heat Stress Disorders; Wounds and Injuries

Intervention Hierarchy (Ancestors)

Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Slawomir Michalak, Prof.

  Poznan University of Medical Sciences

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Slawomir Michalak, Prof.

CONTACT

+48 61 8691 535; swami@ump.edu.pl

Jakub Moskal, MD, PhD

CONTACT

+48 61 8691 422; jakub.moskal@usk.poznan.pl

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Masking Details: ANCHIALE is open-label study
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, PhD, Prof., head of department

Model Details: A prospective longitudinal study will be performed recurrent glioblastoma multiforme patients who: 1. are included for NanoTherm therapy (group A), 2. are included for standard Stupp protocol (surgery/chemo-radiotherapy) (group B)

Study Record Dates

• First Submitted: February 14, 2024
• First Posted: February 21, 2024
• Study Start: January 1, 2024
• Primary Completion (Estimated): February 1, 2027
• Study Completion (Estimated): September 1, 2027
• Last Updated: February 26, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will not share

Locations

PL (1)