PriCoTTF Study: TTFields Before and During Radiotherapy for Newly Diagnosed Glioblastoma

PriCoTTF Study: A Phase I/II Study With TTFields Before and During Radiotherapy in Newly Diagnosed Glioblastoma

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.

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 Exclusion Criteria:

• Subjects not able to give consent
• Subject without legal capacity who is unable to understand the nature, scope, significance, and consequences of this clinical trial
• Simultaneously participation in another clinical trial or participation in any clinical trial involving administration of an investigational medicinal product within 30 days prior to clinical trial beginning
• Subjects with a physical or psychiatric condition which at the investigator´s discretion may put the subject at risk, may confound the trial results or may interfere with the subject's participation in this clinical trial
• Known or persistent abuse of medication, drugs or alcohol

Exclusion criteria regarding special restrictions for females:

• Current or planned pregnancy or nursing women
• Females of child-bearing potential, who are not using and not willing to use medically reliable methods of contraception for the entire study duration (such as oral, injectable, or implantable contraceptives, or intrauterine contraceptive devices) unless they are surgically sterilized / hysterectomized or there are any other criteria considered sufficiently reliable by the investigator in individual cases

Indication-specific exclusion criteria:

• Infra-tentorial tumor

• Significant comorbidities at baseline, which would prevent possible chemotherapy, including:

  • Platelet count < 100/nl
  • Absolute neutrophil count (ANC) < 1.5/nl
  • Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 3 times the upper limit of normal
  • Total bilirubin above the normal range
  • Serum creatinine > 1.7 mg/dl

• Patients with clinically significant liver-, renal- or blood disorder

• Patients with known additional significant neurological disease (e.g. primary seizure disorder*, dementia, progressive degenerative neurological disease, meningitis or encephalitis, hydrocephalus with increased intracranial pressure)

  *Patients with brain tumor-related epilepsy, seizure-free under antiepileptic therapy are eligible

• Documented allergy to conductive hydrogel (e.g. ECG (electrocardiogram) sticker or TENS (transcutaneous electrical nerve stimulation) electrodes

• Active implanted medical device (e.g. deep brain stimulators, spinal cord stimulators, vagus nerve stimulators, pacemakers, defibrillators and programmable shunts)or documented clinically significant arrhythmias

• Skull defect (e.g. missing bone with no replacement) and bullet fragments in the skull

• History of hypersensitivity reaction to temozolomide or lomustine

• Positive human immunodeficiency virus (HIV) Test