- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03258021
TTFields In GErmany in Routine Clinical Care (TIGER)
The Use of TTFields for Newly Diagnosed GBM Patients in Germany in Routine Clinical Care - TIGER Study
Study Overview
Detailed Description
Glioblastoma (GBM) is the most common malignant primary tumor of the brain. The current standard of care for patients with newly diagnosed GBM consists of maximal surgical resection, approx. 60 Gy of radiotherapy together with chemotherapy using temozolomide (TMZ), followed by maintenance TMZ for 6 months. This treatment scheme was shown to extend median survival from 12.1 to 14.6 months compared to surgery and radiotherapy alone. This survival was essentially unchanged since 2005 despite numerous clinical Phase 3 trials conducted.
Although immense efforts were made over the years with different treatment strategies, the survival of patients with newly diagnosed GBM remained very poor until recently. Tumor-treating fields (TTFields) are low-intensity, intermediate frequency, alternating electric fields delivered continuously through adhesive patches, called transducer arrays, to the area of the brain where the GBM tumor is located and help slow down or stop glioblastoma cancer cells from dividing. These transducer arrays are applied to the scalp and are connected to the wearable and portable device.
TTFields are the first treatment since 2005 to demonstrate significantly extended median overall survival and significantly improved long-term survival (one to five year survival rates) compared to the current standard of care. In addition, TTFields significantly extended progression-free survival.
In the Phase 3 trial in newly diagnosed GBM (trial EF-14) the results demonstrated that the addition of TTFields to maintenance TMZ significantly extends both, median and long term survival, as well as progression free survival of patients with newly diagnosed GBM. The magnitude of survival benefit seen is even better to that seen for addition of TMZ to radiation, which established TMZ as the standard of care for 1st line GBM treatment in 2005. Quality of life (QoL) was maintained with the use of TTFields + TMZ in patients for whom 12 months of QoL data were available. The addition of TTFields to TMZ therapy in patients with newly diagnosed glioblastoma was not associated with any significant increase in systemic toxic effects compared with TMZ therapy alone. The most commonly reported side effect from the delivery of TTFields was a mild-to-moderate skin irritation beneath the transducer arrays.
Study Type
Enrollment (Actual)
Contacts and Locations
Study Locations
-
-
Bavaria
-
Aschaffenburg, Bavaria, Germany, 63739
- Clinical center Aschaffenburg-Alzenau
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Sampling Method
Study Population
Description
Inclusion Criteria:
- Newly diagnosed histologically confirmed GBM (WHO-Grade IV)
- Patient within first 3 cycles of first-line tumor-specific maintenance chemotherapy
- ≥ 18 years of age
- Clinical indication for TTFields treatment
- Given informed consent for use and processing of data
Exclusion Criteria:
- Present or planned pregnancy
- Significant additional neurological disease (e.g. significantly increased intracerebral pressure (ICP) with a significant midline shift of the brain)
- Active implanted medical device (e.g. deep brain stimulator)
- Documented allergy to conductive hydrogel
- Skull defect (e.g. missing bone with no replacement, bullet fragments in the skull)
Study Plan
How is the study designed?
Design Details
- Observational Models: Other
- Time Perspectives: Prospective
Cohorts and Interventions
Group / Cohort |
Intervention / Treatment |
---|---|
GBM with indication for TTFields
newly diagnosed GBM with clinical indication for TTFields
|
Tumor treating fields (TTFields) help slow down or stop glioblastoma cancer cells from dividing by disrupting dividing mechanism of cancer cells leading to apoptosis.
TTFields are low-intensity, intermediate frequency, alternating electric fields delivered continuously through adhesive patches, called transducer arrays, to the area of the brain where the GBM tumor is located.
These transducer arrays are applied to the scalp and are connected to the wearable and portable device.
TTFields are approved for the treatment of newly diagnosed and recurrent GBM.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Time to death of any cause (overall survival (OS)) from diagnosis
Time Frame: through study completion, an average of 18 months (mean FU time)
|
Time to death of any cause (overall survival (OS)) from diagnosis is measured using the patient data from date of enrollment until the date of death from any cause
|
through study completion, an average of 18 months (mean FU time)
|
Number of TTFields treatment-related serious adverse events (SAEs) standardized to one year of FU time
Time Frame: through study completion, an average of 18 months (mean follow-up time)
|
Number of TTFields treatment-related SAEs standardized to one year of follow-up (FU) is measured using the collection of SAEs during the follow-up period
|
through study completion, an average of 18 months (mean follow-up time)
|
Number of SAEs after start of TTFields treatment
Time Frame: through study completion, an average of 18 months (mean follow-up time)
|
Number of SAEs after start of TTFields treatment is measured using the collection of SAEs at the follow-up period
|
through study completion, an average of 18 months (mean follow-up time)
|
Time of usage (compliance) of TTFields treatment over time
Time Frame: through study completion, an average of 18 months (mean follow-up time)
|
Time of usage (compliance) of TTFields treatment over time is measured using the treatment compliance report at the Follow-up period
|
through study completion, an average of 18 months (mean follow-up time)
|
Time to first progression of GBM (progression-free survival (PFS)), defined within radiological and/or clinical/neurological assessment during routine clinical care in patients who started TTFields treatment at baseline
Time Frame: through study completion, an average of 18 months (mean follow-up time)
|
Time to first progression of GBM (progression-free survival (PFS)), defined within radiological and/or clinical/neurological assessment during routine clinical care in patients who started TTFields treatment at baseline from date of enrollment until the date of first progression of GBM
|
through study completion, an average of 18 months (mean follow-up time)
|
Changes in quality of life at month 2 and month 4 after start of TTFields treatment compared to baseline in patients who started TTFields treatment at baseline
Time Frame: month 2 and month 4 after start of TTFields treatment compared to baseline in patients who started TTFields treatment at baseline
|
Changes in quality of life assessed via questionnaires EORTC Quality of life questionnaires (QLQ) QLQ-C30 and BN20 after start of TTFields treatment compared to baseline in patients who started TTFields treatment at baseline is measured using the QoL questionnaires at months two and four after start of TTFields treatment
|
month 2 and month 4 after start of TTFields treatment compared to baseline in patients who started TTFields treatment at baseline
|
Patients' reason(s) for refusing TTFields at baseline
Time Frame: baseline
|
Patients' reason(s) for refusing TTFields is measured using a study specific questionnaire at baseline
|
baseline
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Oliver Bähr, Prof., Clinical center Aschaffenburg-Alzenau, Aschaffenburg, Germany
Publications and helpful links
General Publications
- 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.
- Stupp R, Taillibert S, Kanner AA, Kesari S, Steinberg DM, Toms SA, Taylor LP, Lieberman F, Silvani A, Fink KL, Barnett GH, Zhu JJ, Henson JW, Engelhard HH, Chen TC, Tran DD, Sroubek J, Tran ND, Hottinger AF, Landolfi J, Desai R, Caroli M, Kew Y, Honnorat J, Idbaih A, Kirson ED, Weinberg U, Palti Y, Hegi ME, Ram Z. Maintenance Therapy With Tumor-Treating Fields Plus Temozolomide vs Temozolomide Alone for Glioblastoma: A Randomized Clinical Trial. JAMA. 2015 Dec 15;314(23):2535-43. doi: 10.1001/jama.2015.16669.
- 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. Erratum In: JAMA. 2018 May 1;319(17):1824.
- Kirson ED, Gurvich Z, Schneiderman R, Dekel E, Itzhaki A, Wasserman Y, Schatzberger R, Palti Y. Disruption of cancer cell replication by alternating electric fields. Cancer Res. 2004 May 1;64(9):3288-95. doi: 10.1158/0008-5472.can-04-0083.
- Kirson ED, Dbaly V, Tovarys F, Vymazal J, Soustiel JF, Itzhaki A, Mordechovich D, Steinberg-Shapira S, Gurvich Z, Schneiderman R, Wasserman Y, Salzberg M, Ryffel B, Goldsher D, Dekel E, Palti Y. Alternating electric fields arrest cell proliferation in animal tumor models and human brain tumors. Proc Natl Acad Sci U S A. 2007 Jun 12;104(24):10152-7. doi: 10.1073/pnas.0702916104. Epub 2007 Jun 5.
- Gera N, Yang A, Holtzman TS, Lee SX, Wong ET, Swanson KD. Tumor treating fields perturb the localization of septins and cause aberrant mitotic exit. PLoS One. 2015 May 26;10(5):e0125269. doi: 10.1371/journal.pone.0125269. eCollection 2015.
- Giladi M, Schneiderman RS, Voloshin T, Porat Y, Munster M, Blat R, Sherbo S, Bomzon Z, Urman N, Itzhaki A, Cahal S, Shteingauz A, Chaudhry A, Kirson ED, Weinberg U, Palti Y. Mitotic Spindle Disruption by Alternating Electric Fields Leads to Improper Chromosome Segregation and Mitotic Catastrophe in Cancer Cells. Sci Rep. 2015 Dec 11;5:18046. doi: 10.1038/srep18046.
- Stupp R, Wong ET, Kanner AA, Steinberg D, Engelhard H, Heidecke V, Kirson ED, Taillibert S, Liebermann F, Dbaly V, Ram Z, Villano JL, Rainov N, Weinberg U, Schiff D, Kunschner L, Raizer J, Honnorat J, Sloan A, Malkin M, Landolfi JC, Payer F, Mehdorn M, Weil RJ, Pannullo SC, Westphal M, Smrcka M, Chin L, Kostron H, Hofer S, Bruce J, Cosgrove R, Paleologous N, Palti Y, Gutin PH. NovoTTF-100A versus physician's choice chemotherapy in recurrent glioblastoma: a randomised phase III trial of a novel treatment modality. Eur J Cancer. 2012 Sep;48(14):2192-202. doi: 10.1016/j.ejca.2012.04.011. Epub 2012 May 18.
- Kanner AA, Wong ET, Villano JL, Ram Z; EF-11 Investigators. Post Hoc analyses of intention-to-treat population in phase III comparison of NovoTTF-100A system versus best physician's choice chemotherapy. Semin Oncol. 2014 Oct;41 Suppl 6:S25-34. doi: 10.1053/j.seminoncol.2014.09.008. Epub 2014 Sep 16. Erratum In: Semin Oncol. 2015 Jun;42(3):e56-66.
- Dolecek TA, Propp JM, Stroup NE, Kruchko C. CBTRUS statistical report: primary brain and central nervous system tumors diagnosed in the United States in 2005-2009. Neuro Oncol. 2012 Nov;14 Suppl 5(Suppl 5):v1-49. doi: 10.1093/neuonc/nos218. No abstract available. Erratum In: Neuro Oncol. 2013 May;15(5):646-7.
- Kesari S, Ram Z; EF-14 Trial Investigators. Tumor-treating fields plus chemotherapy versus chemotherapy alone for glioblastoma at first recurrence: a post hoc analysis of the EF-14 trial. CNS Oncol. 2017 Jul;6(3):185-193. doi: 10.2217/cns-2016-0049. Epub 2017 Apr 12.
- Mrugala MM, Engelhard HH, Dinh Tran D, Kew Y, Cavaliere R, Villano JL, Annenelie Bota D, Rudnick J, Love Sumrall A, Zhu JJ, Butowski N. Clinical practice experience with NovoTTF-100A system for glioblastoma: The Patient Registry Dataset (PRiDe). Semin Oncol. 2014 Oct;41 Suppl 6:S4-S13. doi: 10.1053/j.seminoncol.2014.09.010. Epub 2014 Sep 16. Erratum In: Semin Oncol. 2015 Jun;42(3):e33-43.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- 05.07.2017
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Glioblastoma
-
Celldex TherapeuticsCompletedGlioblastoma | Gliosarcoma | Recurrent Glioblastoma | Small Cell Glioblastoma | Giant Cell Glioblastoma | Glioblastoma With Oligodendroglial Component | Relapsed GlioblastomaUnited States
-
Juan M Garcia-GomezHospital Universitario 12 de Octubre; Hospital Clínico Universitario de ValenciaRecruitingGlioblastoma | Glioblastoma Multiforme | High Grade Glioma | Astrocytoma, Grade IV | Glioblastoma, IDH-mutant | Glioblastoma, IDH-wildtype | Glioblastoma IDH (Isocitrate Dehydrogenase) Wildtype | Glioblastoma IDH (Isocitrate Dehydrogenase) MutantSpain
-
Jasper GerritsenMassachusetts General Hospital; Universitaire Ziekenhuizen KU Leuven; University... and other collaboratorsRecruitingGlioblastoma | Glioblastoma Multiforme | Glioblastoma, IDH-wildtype | Glioblastoma Multiforme, Adult | Glioblastoma Multiforme of BrainUnited States, Belgium, Switzerland, Germany, Netherlands
-
Jasper GerritsenMassachusetts General Hospital; Universitaire Ziekenhuizen KU Leuven; University... and other collaboratorsRecruitingGlioblastoma | Glioblastoma Multiforme | Recurrent Glioblastoma | Glioblastoma, IDH-wildtype | Glioblastoma Multiforme, Adult | Glioblastoma Multiforme of Brain | Astrocytoma of Brain | Astrocytoma, MalignantUnited States, Germany, Netherlands, Switzerland, Belgium
-
Leland MethenyNational Cancer Institute (NCI)RecruitingGlioblastoma Multiforme | Supratentorial Gliosarcoma | Glioblastoma Multiforme, Adult | Supratentorial GlioblastomaUnited States
-
Northwestern UniversityAgenus Inc.; CarTheraRecruitingGlioblastoma Multiforme | Gliosarcoma | Newly Diagnosed Glioblastoma | Glioblastoma, Isocitric Dehydrogenase (IDH)-WildtypeUnited States
-
University Hospital, GenevaActive, not recruitingGlioblastoma Multiforme | Glioblastoma Multiforme of Brain | Glioma of Brain | Glioblastoma, AdultSwitzerland
-
Milton S. Hershey Medical CenterRecruitingGlioblastoma | Glioblastoma Multiforme | Glioblastoma Multiforme, Adult | Glioblastoma Multiforme of BrainUnited States
-
Northwestern UniversityNational Cancer Institute (NCI)RecruitingGlioblastoma | Astrocytoma | Recurrent Glioblastoma | MGMT-Unmethylated Glioblastoma | Glioblastoma, IDH-WildtypeUnited States
-
Milton S. Hershey Medical CenterNational Cancer Institute (NCI)RecruitingGlioblastoma | Glioblastoma Multiforme | Glioblastoma Multiforme, Adult | Glioblastoma Multiforme of BrainUnited States
Clinical Trials on TTFields
-
The Christie NHS Foundation TrustNorthern Care Alliance NHS Foundation Trust; NovoCure Ltd.; University of ManchesterNot yet recruitingGlioblastoma
-
NovoCure GmbHRecruitingPleural MesotheliomaGermany, Italy
-
Sun Yat-sen UniversityUnknown
-
NovoCure Ltd.Recruiting
-
Zhongnan HospitalNot yet recruitingGlioma | GlioblastomaChina
-
Juergen DebusWithdrawnNewly Diagnosed Glioblastoma in Patients ≥70 YearsGermany
-
Medical College of WisconsinRecruiting
-
OHSU Knight Cancer InstituteOregon Health and Science University; NovoCure Ltd.TerminatedStage IVA Lung Cancer AJCC v8 | Stage IVB Lung Cancer AJCC v8 | Stage III Lung Cancer AJCC v8 | Stage IV Lung Cancer AJCC v8 | Stage II Lung Cancer AJCC v8 | Stage IIA Lung Cancer AJCC v8 | Stage IIB Lung Cancer AJCC v8 | Stage IIIA Lung Cancer AJCC v8 | Stage IIIB Lung Cancer AJCC v8 | Extensive Stage... and other conditionsUnited States
-
Nir PeledNot yet recruitingNon Small Cell Lung Cancer | EGFR Gene Mutation | Immune Checkpoint InhibitorIsrael
-
Emory UniversityNational Cancer Institute (NCI)Recruiting