A Phase II Study of TTFields (150 kHz) Concomitant With Gemcitabine and TTFields Concomitant With Gemcitabine Plus Nab-paclitaxel for Front-line Therapy of Advanced Pancreatic Adenocarcinoma
试验速览
- 阶段
- 1 期
- 入组人数
- 40
- 试验地点
- 6
- 主要终点
- Adverse Events Severity and Frequency
研究概览
简要总结
The study is a prospective, double arm, non-randomized, open label pilot trial, designed to study the safety, feasibility and preliminary efficacy of a medical device, the NovoTTF-100L concomitant with gemcitabine or concomitant with gemcitabine plus nab-paclitaxel, for front-line therapy of pancreatic adenocarcinoma. 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 generated by the NovoTTF-100L device (TTFields, TTF) has demonstrated significant activity in in vitro and in vivo pancreatic adenocarcinoma pre-clinical models both as a single modality treatment, in combination with gemcitabine and in combination with paclitaxel. TTFields therapy has also shown to inhibit metastatic spread of malignant melanoma in in vivo experiment.
In a small scale pilot study, 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 treated 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 treated subjects as a group when compared to subjects receiving effective best standard of care chemotherapy.
In a large prospective, randomized trial, in newly diagnosed GBM, TTFields in combination with standard-of-care temozolomide chemotherapy extended both progression-free survival and overall survival compared to temozolomide alone. There was no significant increase in serious adverse events from TTFields in combination with temozolomide versus temozolomide alone. The most common adverse reaction from TTFields treatment was mild to moderate skin irritation.
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
- •Diagnosis of unresectable locally advanced or metastatic adenocarcinoma of the pancreas with histologically or cytologically confirmed disease.
- •18 years of age and older
- •Life expectancy of at least 12 weeks
- •Measureable or assessable disease according to the revised RECIST criteria version 1.
- •ECOG (Eastern Cooperative Oncology Group) score 0-1
- •Adequate bone marrow, liver and kidney function:
- •Absolute neutrophil count ≥ 1.5 x 10^9/L
- •Platelet count ≥ 100 x 10^9/L
- •Hemoglobin ≥ 10 g/dL
- •AST and/or ALT ≤ 3 x upper limit of normal range (ULN) or ≤ 5 x ULN if patient has documented liver metastases
- •Bilirubin ≤1.5 x ULN
- •Serum creatinine ≤ 1.5 x ULN
- •Coagulation status: PT and PTT within normal limits or within therapeutic limits for patients receiving anticoagulation.
- •Able to operate the NovoTTF-100L System independently or with the help of a caregiver.
- •No concurrent anti-tumor therapy (beyond gemcitabine or gemcitabine and nab-paclitaxel and TTField therapy as per protocol).
- •No prior chemotherapy or radiation allowed.
- •At least 4 weeks since major surgery.
- •Prior surgery allowed for local disease provided a measurable lesion remains on the baseline CT scan.
- •Signed informed consent form
排除标准
- •Known brain metastases or meningeal carcinomatosis.
- •Any other malignancy requiring anti-tumor treatment in the past three years.
- •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.
- •Implantable electronic medical devices including pacemaker, implantable automatic defibrillator, etc.
- •Known allergies to medical adhesives or hydrogel or nab-paclitaxel.
- •Pregnant or breast feeding.
- •Admitted to an institution by administrative or court order
研究组 & 干预措施
TTFilelds + gemcitabine
Patients will be treated continuously with the NovoTTF-100L device, in addition to Gemcitabine.
干预措施: NovoTTF-100L (Device)
TTFilelds + gemcitabine
Patients will be treated continuously with the NovoTTF-100L device, in addition to Gemcitabine.
干预措施: Gemcitabine (Drug)
TTFields + gemcitabine+ nab-paclitaxel
Patients will be treated continuously with the NovoTTF-100L device, in addition to Gemcitabine plus nab-paclitaxel
干预措施: NovoTTF-100L (Device)
TTFields + gemcitabine+ nab-paclitaxel
Patients will be treated continuously with the NovoTTF-100L device, in addition to Gemcitabine plus nab-paclitaxel
干预措施: Gemcitabine (Drug)
TTFields + gemcitabine+ nab-paclitaxel
Patients will be treated continuously with the NovoTTF-100L device, in addition to Gemcitabine plus nab-paclitaxel
干预措施: nab-Paclitaxel (Drug)
结局指标
主要结局
Adverse Events Severity and Frequency
时间窗: 1.5 years
Feasibility based on compliance with TTFields therapy
时间窗: 1.5 yeras
次要结局
- Overall Response Rate based on RECIST (Response Evaluation Criteria in Solid Tumors) criteria 1.1.(1.5 years)
- 1 Year Survival Rate(1.5 years)
- 6 Month Progression-Free Survival Rate(1.5 years)
- Progression Free Survival(1.5 years)
- Overall Survival(1.5 years)