HEPANOVA: a Phase II Trial of Tumor Treating Fields (TTFields, 150kHz) Concomitant with Sorafenib for Advanced Hepatocellular Carcinoma (HCC)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 25
- 试验地点
- 8
- 主要终点
- Overall response rate
研究概览
简要总结
The study is a prospective, phase II trial single arm, historical control aimed to test the efficacy and safety of TTFields, using the NovoTTF-100L(P) System, in combination with sorafenib in patient with advanced HCC. The device is an experimental, portable, battery operated device for chronic administration of alternating electric fields (termed TTFields or TTF) to the region of the malignant tumor, by means of surface, insulated electrode arrays.
详细描述
PAST PRE-CLINICAL AND CLINICAL EXPERIENCE:
The effect of the electric fields (TTFields, TTF) has demonstrated significant activity in in vitro hepatocellular carcinoma pre-clinical models. In addition, TTFields have shown to inhibit metastatic spread of malignant melanoma in in vivo experiment.
In pilot study, 40 patients with locally advanced or metastatic pancreatic adenocarcinoma received chemotherapy with TTFields (150 kHz) applied to the abdomen. The combination was well tolerated and the only device-related adverse event was contact dermatitis.
In addition, a phase III trial of Optune® (200 kHz) as monotherapy compared to active chemotherapy in recurrent glioblastoma patients showed TTFields to be equivalent to active chemotherapy in extending survival, associated with minimal toxicity, good quality of life, and activity within the brain (14% response rate) (Stupp R., et al., EJC 2012). Finally, a phase III trial of Optune® combined with maintenance temozolomide compared to maintenance temozolomide alone has shown that combined therapy led to a significant improvement in both progression free survival and overall survival in patients with newly diagnosed glioblastoma without the addition of high grade toxicity and without decline in quality of life (Stupp R., et al., JAMA 2017).
DESCRIPTION OF THE TRIAL:
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 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
- •HCC diagnosed by biopsy, or by imaging criteria (CT/MRI) and AFP
- •≥ 18 years of age
- •Barcelona Clinic Liver Cancer Staging (BCLC) Stage 0-C
- •Child-Turcotte-Pugh (CTP) score between 5 and 8 points
- •Measurable disease per RECIST Criteria
- •At least 4 weeks since major surgery
- •ECOG Performance Status (PS) of 0-2
- •Life expectancy of at least 12 weeks
- •All subjects must sign written informed consent
- •Able to operate the NovoTTF-100L(P) System independently or with the help of a caregiver.
排除标准
- •Patient candidate for surgical resection or local treatment (e.g. TACE, SIRT, RFTA, microwave, surgery)
- •High levels of serum HBV DNA without anti-viral therapy
- •Prior malignancy requiring anti-tumor treatment (apart from in-situ cervical cancer, in situ breast cancer, non-melanomatous skin cancers, or any malignancy for which treatment was received and there is no evidence of disease for at least 5 years) or concurrent malignancy.
- •Significant co-morbidities within 4 weeks prior to enrollment, including the following:
- •neurologic or psychiatric disorders such as dementia and uncontrolled seizures
- •active, uncontrolled infections
- •active, disseminated coagulation disorder
- •Significant renal impairment
- •Clinically significant cardiovascular disease (including myocardial infarction, unstable angina, symptomatic congestive heart failure, serious uncontrolled cardiac arrhythmia)
- •Chronic diarrhea
- •History of any psychological or psychiatric condition that might impair the patient's ability to understand or comply with the requirements of the study or to provide consent.
- •Other co-morbidities deemed by the investigator as such that may impact the compliance of the patient with the study protocol and follow up
- •Implanted pacemaker, defibrillator or other electrical medical devices in the torso
- •Known allergies to medical adhesives or hydrogel
- •Pregnant or breast feeding (all patients of childbearing potential must use effective contraception method during the entire period of the study based on the recommendation of the investigator or a gynecologist)
- •Admitted to an institution by administrative or court order
研究组 & 干预措施
TTFields in combination with sorafenib
Patients will be treated continuously with TTFields, in addition to sorafenib
干预措施: NovoTTF-100L(P) device (Device)
TTFields in combination with sorafenib
Patients will be treated continuously with TTFields, in addition to sorafenib
干预措施: Sorafenib (Drug)
结局指标
主要结局
Overall response rate
时间窗: 30 months
The percentage of patients who had either complete response or partial response per RECIST criteria following enrollment in the trial.
次要结局
- In-field control rate at one year(12 months)
- Progression Free Survival(30 months)
- Overall survival at one year(12 months)
- Overall survival(30 months)
- Distant metastases-free survival rate at 1 year(12 months)
- Progression free survival at 6 and 12 months(12 months)
- Severity and frequency of adverse events(30 months)