Glioblastoma Multiforme (GBM)
Conditions
Keywords
newly-diagnosed glioblastoma, TTFields, Tumor Treating Fields, radiotherapy, chemotherapy
Brief summary
The PriCoTTF clinical trial is related to the development and validation of the investigational product Optune®, a device for generating tumor therapy fields (TTFields) that is used in combination with radiation therapy to treat newly diagnosed glioblastoma. The trial aims to evaluate the safety of early and concurrent use of TTFields with standard radiation chemotherapy. This strategy is based on preclinical data suggesting that TTFields increase the sensitivity of tumor cells to radiation therapy. Critical components of this clinical trial include demonstrating the safety and tolerability of TTFields in combination with radiation therapy and collecting initial efficacy data. The target population consists of patients with newly diagnosed glioblastoma, with treatment beginning immediately after surgical resection and continuing for up to nine months. Follow-up examinations will be conducted at regular intervals to monitor long-term treatment success. The trial protocol was developed in accordance with the guidelines of the International Conference on Harmonisation (ICH) Good Clinical Practice (GCP). In addition, discussions were held between the sponsor, Essen University Hospital, and the relevant regulatory authorities to ensure that the clinical trial complies with regulatory requirements and is ethically acceptable. Compliance with these standards ensures scientific validity and patient safety throughout the study.
Interventions
DEVICETTFields before and during radiotherapy
Administration of TTFields before and during radiation therapy in patients with primary glioblastoma (Arm A)
Sponsors
Sied Kebir
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* At least 18 years of age * Pathological evidence of glioblastoma or gliosarcoma using latest World Health Organization (WHO) classification criteria * Negative isocitrate dehydrogenase (IDH) status on immunohistochemistry or sequencing * Patient received brain tumor resection or biopsy and further treatment regime foresees radiotherapy with or without concomitant chemotherapy * General indication for whole treatment regimen was a common decision of a multidisciplinary team within brain tumor board and in accordance with the national and/or international guidelines for the treatment of glioblastoma patients * KPS ≥ 60% (Study arm A), KPS ≥ 50% (Study arm B) * Life expectancy at least 3 months * Participants of child-bearing age must use effective contraception * Treatment with Tumor Treating Fields (TTFields) may start 2-4 weeks post resection and 1-2 weeks prior to radiotherapy * Subjects with the ability to follow study instructions and likely to attend and complete all required visits * Written informed consent of the subject
Exclusion criteria
General
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Feasibility and safety (frequency of predefined treatment-limiting toxicities (TLTs)) of Tumor Treating Fields (TTFields) before and concurrently with radiation therapy in patients with primary glioblastoma | From the day of surgery until 4 weeks after end of radiotherapy (usually 10-12 weeks) | The primary endpoint is safety and tolerability. It is based on the frequency of predefined treatment-limiting toxicities (TLTs), which are assessed weekly during therapy and up to four weeks after the end of radiation therapy. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall survival (OS) | From tumor diagnosis to death (usually 6 to 24 months) | Overall survival from diagnosis to death |
| Quality of life (QoL) | At end of radiotherapy (usually 3-10 weeks after randomization); 4 weeks after the end of radiotherapy; at 3, 5 and 7 months of TTFields treatment | The following questionnaires are used to assess quality of life: EORTC Core Quality of Life Questionnaire \[QLQ-C30\], (Part A with 28 questions on a Likert scale, 28 to 112 points, Higher score means lower quality of life; Part B with 2 questions on a Likert scale, 2 to 14 points, Lower score means lower quality of life) EORTC Brain Questionaire \[QLQ-BN20\], (20 questions on a Likert scale; 20 to 80 points; Higher score means lower quality of life) |
| Estimation number of fully compliant patients | Usually 7 to 12 weeks | Fully compliant is defined as: Wearing rate of TTFields must be at least 50% between randomisation and visit 4 (4 weeks after the end of radiotherapy). |
| Estimation of the delivered cumulative dose distribution | From beginning to the end of radiotherapy (usually 3-6 weeks) | Estimation of the delivered cumulative dose distribution over the treatment series for each patient from the KV-image guidance data and comparison with the planned dose distribution. Dose deviations by more than 3.5% in more than 1 cm3 within the PTV or if more than 5% in less than 1 cm3 will be considered as relevant |
| Number of patients with ≥ grade 3 skin toxicity (Common Terminology Criteria for Adverse Events, CTCAE) | Until the end of treatment or tumor recurrence, whichever occurs first (usually 6 to 24 months) | Number of patients with ≥ grade 3 skin toxicity (CTCAE) separately into patients with high 1 and low radiation risk. 1: high risk group: patients who received a surface dose \>70% of the prescribed dose within or up to 6 mm below the skin on a scalp area are of \>50 cm2 |
| Long-term treatment-limiting toxicities (TLTs) | Until the end of treatment or tumor recurrence, whichever occurs first (usually 6 to 24 months) | TLT 4 weeks after radiotherapy completion until the end of treatment or tumor recurrence, whichever occurs first (overall and considering concomitant chemotherapy) |
| Short-term treatment-limiting toxicities (TLTs) | During (usually 3-6 weeks) radiotherapy and up to 4 weeks after the end of radiotherapy | TLT during treatment and up to 4 weeks after end of radiotherapy concomitant chemotherapy |
| Progession free survival (PFS) | Until tumor recurrence (usually 6 to 12 months) | Time from diagnosis to MRI based tumor progression |
| Radiological response (RANO criteria) | Until the end of treatment or tumor recurrence, whichever occurs first (usually 6 to 24 months) | The radiological response is assessed during regular MRI follow-up examinations. |
| Adverse events as measured by Common Terminology Criteria for Adverse Events (CTCAE) | Until the end of treatment or tumor recurrence, whichever occurs first (usually 6 to 24 months) | Adverse events are classified according to CTCAE |
Other
| Measure | Time frame | Description |
|---|---|---|
| Exploratory endpoint: Progression free survival (PFS) from first to second tumor progression | First to second progression (usually after 6 to 24 monts) | PFS from first to second tumor progression (under consideration of TTFields re-challenge) |
| Exploratory endpoint: Overall survival (OS) | First to second progression (usually 6 to 24 monts) | OS from first to second tumor progression (under consideration of TTFields re-challenge) |
| Exploratory endpoint: Assessment of Tumor Progression Patterns | At progression (usually 6 to 12 months) | An investigation of tumor progression patterns will be conducted with regard to specific characteristics under experimental therapy. |
| Exploratory endpoint: Frequency of grade 1-4 white matter lesions | at 4 weeks (Visit 4) and 6 months (Visit 7) or tumor progression (Visit P) after the end of radiotherapy (usually 6 to 12 months) | Frequency of grade 1-4 white matter lesions at 4 weeks (Visit 4) and 6 months (Visit 7) or tumor progression (Visit P) after the end of radiotherapy until tumor progression (MRI according to visit schedule) |
Countries
Germany
Outcome results
None listed