PriCoTTF Study: A Phase I/II Study With TTFields Before and During Radiotherapy in Newly Diagnosed Glioblastoma
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 33
- 试验地点
- 2
- 主要终点
- 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
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
结局指标
主要结局
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
时间窗: 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.
次要结局
- Radiological response (RANO criteria)(Until the end of treatment or tumor recurrence, whichever occurs first (usually 6 to 24 months))
- Long-term treatment-limiting toxicities (TLTs)(Until the end of treatment or tumor recurrence, whichever occurs first (usually 6 to 24 months))
- Short-term treatment-limiting toxicities (TLTs)(During (usually 3-6 weeks) radiotherapy and up to 4 weeks after the end of radiotherapy)
- Progession free survival (PFS)(Until tumor recurrence (usually 6 to 12 months))
- Overall survival (OS)(From tumor diagnosis to death (usually 6 to 24 months))
- 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))
- 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)
- 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))
- Estimation number of fully compliant patients(Usually 7 to 12 weeks)
- Estimation of the delivered cumulative dose distribution(From beginning to the end of radiotherapy (usually 3-6 weeks))
研究者
Sied Kebir
PD. Dr. med., Head of Clinical Neuro-Oncology
University Hospital, Essen