Trial Title:
NanoTherm In Adjuvant Therapy of Glioblastoma Multiforme
NCT ID:
NCT06271421
Condition:
Glioblastoma Multiforme
Conditions: Official terms:
Glioblastoma
Temozolomide
Conditions: Keywords:
glioblastoma
adjuvant therapy
hyperthermia
NanoTherm
GBM
Study type:
Interventional
Study phase:
N/A
Overall status:
Recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Parallel Assignment
Intervention model description:
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)
Primary purpose:
Treatment
Masking:
None (Open Label)
Masking description:
ANCHIALE is open-label study
Intervention:
Intervention type:
Device
Intervention name:
NanoTherm therapy
Description:
Cyclic hyperthermia in patients with recurrent glioblastoma multiforme, who underwent
implantation of iron oxide nanoparticles.
Arm group label:
NanoTherm arm (group A)
Other name:
Cyclic hyperthermia
Intervention type:
Procedure
Intervention name:
Glioma Resection
Description:
Removal of brain tumor - gross total ressection
Arm group label:
NanoTherm arm (group A)
Arm group label:
Stupp protocol (group B)
Other name:
Surgical removal of Glioma tumor
Intervention type:
Radiation
Intervention name:
radiotherapy according to Stupp protocol
Description:
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.
Arm group label:
Stupp protocol (group B)
Intervention type:
Drug
Intervention name:
chemotherapy according to Stupp protocol
Description:
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.
Arm group label:
Stupp protocol (group B)
Other name:
temozolomide
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.
Detailed description:
Glioblastoma multiforme (GBM) is the most frequent glial tumor (glioma). The epidemiology
of brain gliomas depends on many factors such as age, gender, genetics, environment, and
lifestyle.
According to statistics, in developed countries, brain gliomas account for about 2% of
all tumors. In the USA, there are approximately 12,000 new cases of brain gliomas
annually, and in Europe, there are about 25,000. The average age of individuals diagnosed
with brain gliomas is 64 years, although they can occur in all age groups. However, the
majority of cases are diagnosed in individuals between 45 and 70 years of age. The global
incidence rate is 3.7/100,000 for men and 2.6/100,000 for women. A higher incidence rate
is observed in highly industrialized countries. It is estimated that gliomas account for
30 to 40% of all intracranial tumors. Approximately 50% of adult gliomas are the most
malignant form - Glioblastoma multiforme G4.
In 2009, 1444 new cases of malignant brain tumors were recorded in men and 1362 in women
in Poland. Men have a slightly higher risk of developing brain gliomas than women. The
presence of genetic and hereditary factors, including mutations in genes related to DNA
repair and cell cycle control, increases the risk of developing gliomas. Risk factors for
the development of gliomas include exposure to ionizing radiation and viral infections
(cytomegalovirus), smoking, alcohol abuse, overweight, lack of physical activity, as well
as exposure to certain chemicals such as pesticides and solvents.
Recommendations for the treatment of Glioblastoma multiforme include:
Surgical removal of the tumor as the primary method of treatment. Unfortunately,
considering the fact that Glioblastoma multiforme is a disease of the entire brain,
complete tumor resection is not possible. Therefore, the use of radiotherapy and/or
chemotherapy is considered. This treatment is used according to the protocol published by
Stupp in 2005.
Radiotherapy: Radiotherapy is used to destroy the remaining tumor cells after the tumor
removal. It can be used after surgery or as a standalone treatment, especially in cases
where the tumor cannot be surgically removed. 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.
Chemotherapy: In the Stupp protocol, 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.
However, the clinical effects of using the Stupp protocol are not fully satisfactory. The
two-year survival rate after the full Stupp protocol (radio- and chemotherapy) is 26.5%
of patients, and after using only radiotherapy, it is 10.4% of patients.
Supportive treatment methods used in the treatment of Glioblastoma multiforme so far
include thermotherapy - hyperthermia and nanotherapy.
Hyperthermia involves:
- the use of elevated temperature to increase the effectiveness of radio- and
chemotherapy
- thermoablation, in which the use of high temperatures - above 45°C - causes direct
damage to tumor cells,
- magnetic hyperthermia (MHT), e.g. NanoTherm® Therapy (NTT), which has been
registered in Europe as a method of treating Glioblastoma multiforme in cases of
tumor recurrence Nanotherapy uses magnetic nanoparticles (MNP), which are used in
diagnostic and therapeutic procedures.
Hyperthermia and thermotherapy have been treatment methods studied in cancer patients and
magnetic hyperthermia induced using nanoparticles is becoming the subject of increasingly
advanced research.
In a phase III study, the use of tumor-treating fields (TTF) was evaluated as a
first-line therapy in patients with Glioblastoma multiforme. Low-power electromagnetic
fields using long waves are directed at the tumor area using external electrodes.
According to the report from the Institute for Quality and Efficiency in Health Care
(IQWiG), this method resulted in a 5-month extension of the overall survival of patients
with Glioblastoma multiforme compared to patients treated with temozolomide, and the
tolerance of the treatment was acceptable.
On the other hand, NanoTherm therapy represents a promising form of thermotherapy leading
to an extension of survival, especially in cases of Glioblastoma multiforme recurrence.
In the study by Maier-Hauff et al., it was shown that the average overall survival of
patients undergoing NanoTherm therapy after recurrence was 13.4 months, which was longer
(P<0.01) than in patients treated according to the Stupp protocol (6.2 months). The
overall survival after the initial diagnosis of Glioblastoma multiforme was also longer
(23.2 versus 14.6 months; P<0.01). The benefit observed in both groups of patients was
attributed to the use of NanoTherm therapy.
Therefore, among the sought-after new methods of treating Glioblastoma multiforme that
could increase the effectiveness of the current treatment, NanoTherm therapy is a
procedure that significantly increases the survival and quality of life of patients. For
this reason, it is planned to conduct this study, the aim of which is to determine the
effectiveness and tolerance of using nanoparticles in cyclic hyperthermia as adjuvant
therapy in patients with Glioblastoma multiforme.
The main goal of the treatment for each patient with Glioblastoma multiforme is to
prolong survival time and improve the quality of life. According to the literature, the
median overall survival of these patients is 9 - 12 months.
Patients with recurrent glioblastoma multiforme WHO G4 will be included in the ANCHIALE
study.
Study Objective:
The aim of the ANCHIALE study is to prepare a registry that allows for the evaluation of
the efficacy and tolerance of using the NanoTherm therapy system in cases of recurrent
glioblastoma multiforme.
Study Principles:
During the initial visit, a qualification for treatment will be conducted, taking into
account the inclusion and exclusion criteria, i.e., indications and contraindications for
the NanoTherm therapy system. Additionally, an interview, neurological examination, and
surveys regarding daily functioning and quality of life will be conducted.
After qualifying a patient for the study, he or she will undergo standard neurosurgical
operation aimed at partial or, if possible, complete removal of the recurrent brain
tumor. Then, in the place of the removed tumor, NanoTherm ASI will be administered in a
quantity of either 112 or 335 mg/ml of iron particles. This is a sterile suspension of
iron oxide nanoparticles in sterile water, characterized by a high specific ability to
absorb heat associated with its superparamagnetic properties. At the site where the
thickest layer of nanoparticles (NanoTherm® ASI) is applied, a catheter will be implanted
allowing for measurement and control of temperature during the first activation in the
magnetic field of the NanoActivator®.
Between the 6th and 10th day after the neurosurgical procedure, a standard computerized
tomography (CT) scan of the head will be performed for routine postoperative evaluation.
After the first activation (10th day post-implantation of NanoTherm® ASI), the catheter
will be removed. Subsequently, cyclically, for 6 times, the patient will be subjected to
the variable magnetic field of the NanoActivator® to induce hyperthermia, i.e., increase
the temperature of the site after the removed tumor and the surrounding tissues.
Activations will be conducted on the 10th, 14th, 17th, 21st, 24th, and 28th day. The heat
released by the nanoparticles (NanoTherm® ASI) into the surrounding tissue causes
destruction or damage to the cells of the glioblastoma multiforme (hyperthermia effect),
increasing their susceptibility to radiotherapy and chemotherapy.
The patient will then be subjected to detailed observation for 2 years. Observation will
include visits conducted on the 60th, 90th, 150th, 210th, 270th, and 360th day after
surgery, and then every 3 months up to 2 years post-procedure.
On the 6th - 10th, 90th, 150th, 210th, 270th, and 360th day after surgery, and then every
3 months up to 2 years post-procedure, a CT scan with an evaluation of treatment efficacy
will be performed. The treatment effects on CT will be analyzed using RANO (Response
Assessment in Neuro-oncology) scale.
During follow-up visits on the 60th, 90th, 150th, 210th, 270th, and 360th day, and then
every 3 months up to 2 years after the surgical procedure, a neurological examination,
assessment of adverse symptoms, number of potential hospitalizations, number of medical
visits, clinimetric assessment regarding quality of life (EuroQuality of Life-5
dimensions 5- levels [EQ-5D-5L], Neurologic Assessment in Neuro-Oncology [NanoScale 2]),
and clinimetric assessment regarding neurological deficit and degree of disability will
be conducted (modified Rankin scale, Barthel index).
The results from NanoTherm group will be compared to patients undergoing standard
neurosurgical treatment for the abovementioned effects.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Recurrence of glioblastoma multiforme.
2. Age > 18 years.
3. Informed written consent to participate in the study.
4. Karnofsky performance score ≥ 60.
5. Expected survival time > 6 months.
6. Failure of standard treatment according to the Stupp protocol.
7. Cardio-respiratory fitness - allowing to stay for 60 minutes in a lying position in
the field activator.
Exclusion Criteria:
1. Pregnant or breastfeeding women.
2. More than 3 foci of glioblastoma multiforme.
3. Tumor invasion of eloquent or motor areas.
4. Subependymal contrast enhancement in the adjacent brain ventricles.
5. Concurrent immunotherapy for glioblastoma.
6. 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.
7. Electronic implants: pacemakers, cardioverter defibrillators, cochlear implants,
deep brain stimulation (DBS) electrodes.
8. Allergy/hypersensitivity to aminosilanes, iron oxide, acetic acid.
9. Planned or current treatment with electromagnetic field in the Optune®TTF system.
10. Claustrophobia not amenable to control.
11. Painful conditions, musculoskeletal system diseases that prevent staying in a lying
position.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
University Hospital
Address:
City:
Poznań
Zip:
60-355
Country:
Poland
Status:
Recruiting
Contact:
Last name:
Slawomir Michalak, Prof.
Phone:
+4861 8691 535
Email:
swami@ump.edu.pl
Contact backup:
Last name:
Jakub Moskal, MD, PhD
Phone:
+4861 8691 422
Email:
jakub.moskal@usk.poznan.pl
Start date:
January 1, 2024
Completion date:
September 1, 2027
Lead sponsor:
Agency:
Poznan University of Medical Sciences
Agency class:
Other
Collaborator:
Agency:
MagForce USA
Agency class:
Industry
Source:
Poznan University of Medical Sciences
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06271421
https://www.iqwig.de/download/n18-02_tumortherapiefelder-beim-glioblastom_rapid-report_v1-1.pdf?rev=186827
https://doi.org/10.1016/j.inat.2021.101127
