A Phase II Trial of Pemetrexed and Cisplatin or Carboplatin in Combination With TTFields (150 kHz) as First-line Treatment in Malignant Pleural Mesothelioma
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 82
- 试验地点
- 13
- 主要终点
- Overall Survival
研究概览
简要总结
The study is a prospective, single arm, non-randomized, open label phase II trial, designed to study the safety and efficacy of a medical device, the NovoTTF-100L concomitant with Pemetrexed and cisplatin or carboplatin in Malignant Pleural Mesothelioma patients. 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 TTFields has demonstrated significant activity in in vitro mesothelioma pre-clinical models both as a single modality treatment and in combination with pemetrexed and cisplatin, chemotherapies that are commonly used to treat malignant pleural mesothelioma.
In a pilot clinical trial (first in men) TTFields were shown to have an effect as a monotherapy in one patient with malignant pleural mesothelioma when applied to the patient's abdomen (the disease metastasized to the abdomen).
In a pilot study, 42 patients with stage IIIB- IV non-small cell lung cancer (NSCLC) who had had tumor progression after at least one line of prior chemotherapy received pemetrexed together with TTFields applied to the chest and upper abdomen until disease progression. Efficacy endpoints were remarkably high compared to historical data for pemetrexed alone.
In a large prospective, randomized trial, in recurrent glioblastoma (GBM). The outcome of subjects treated with TTFields was compared to those treated with an effective best standard of care chemotherapy (including bevacizumab). TTFields arm subjects had comparable overall survival to subjects receiving the best available chemotherapy in the US today. Similar results showing comparability of TTFields to best standard of care (BSC) chemotherapy were seen in all secondary endpoints. Recurrent GBM patients treated with TTFields in this trial experienced fewer side effects in general, significantly fewer treatment related side effects, and significantly lower gastrointestinal, hematological and infectious adverse events compared to controls. The only device-related adverse events seen were a mild to moderate skin irritation beneath the device electrodes. Finally, quality of life measures were better in TTFields Therapy subjects as a group when compared to subjects receiving effective best standard of care chemotherapy.
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
- •Pathological or histological evidence of mesothelioma
- •≥ 18 years of age
- •Not candidate for curative treatment (surgery or radiotherapy)
- •At least 4 weeks since major surgery
- •At least one measurable or evaluable lesion according to modified RECIST Criteria
- •ECOG Performance Status of 0-1
- •Life expectancy of at least 3 months
- •Participants of childbearing age must use effective contraception as indicated by the investigator
- •All subjects must sign written informed consent.
- •Able to operate the NovoTTF-100L System independently or with the help of a caregiver
排除标准
- •Patient candidate for surgery or radiotherapy with curative intent
- •Previous chemotherapy or radiation
- •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, resulting in the following laboratory findings:
- •Significant liver function impairment:
- •AST or ALT > 3 times the upper limit of normal
- •Total bilirubin ≥ 1.5 times upper limit of normal
- •Significant renal impairment (serum creatinine > 1.7 mg/dL)
- •Coagulopathy (as evidenced by PT or APTT >1.5 times control in subjects not undergoing anticoagulation)
- •Thrombocytopenia (platelet count < 100 x 10^3/μL)
- •Neutropenia (absolute neutrophil count < 1.5 x 10^3/μL)
- •Anemia (Hb < 10 g/dL)
- •Severe acute infection
- •Significant comorbidity which is expected to affect patient's prognosis or ability to receive the combined therapy:
- •History of significant cardiovascular disease unless the disease is well controlled.
- •Significant cardiac disease includes second/third degree heart block; significant ischemic heart disease; poorly controlled hypertension; congestive heart failure of the New York Heart Association (NYHA) Class II or worse (slight limitation of physical activity; comfortable at rest, but ordinary activity results in fatigue, palpitation or dyspnea)
- •History of arrhythmia that is symptomatic or requires treatment. Patients with atrial fibrillation or flutter controlled by medication are not excluded from participation in the trial
- •Active infection or any serious underlying medical condition that would impair the ability of the patient to receive protocol therapy
- •History of any psychiatric condition that might impair the patient's ability to understand or comply with the requirements of the study or to provide consent
- •Untreated brain metastases. Asymptomatic, pretreated brain metastases not requiring steroids are allowed
- •Implanted pacemaker, defibrillator or other electrical medical devices
- •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)
研究组 & 干预措施
TTFields concomitant to pemetrexed plus cisplatin/carboplatin
Patients will be treated continuously with TTFields, in addition to pemetrexed plus cisplatin/carboplatin
干预措施: NovoTTF-100L device (Device)
TTFields concomitant to pemetrexed plus cisplatin/carboplatin
Patients will be treated continuously with TTFields, in addition to pemetrexed plus cisplatin/carboplatin
干预措施: Pemetrexed (Drug)
TTFields concomitant to pemetrexed plus cisplatin/carboplatin
Patients will be treated continuously with TTFields, in addition to pemetrexed plus cisplatin/carboplatin
干预措施: Cisplatin or Carboplatin (Drug)
结局指标
主要结局
Overall Survival
时间窗: 1 year
次要结局
- Progression Free Survival(1 year)
- Response Rate(1 year)
- Toxicity- incidence of adverse events(1 year)