Pivotal, Randomized, Open-label Study of Tumor Treating Fields (TTFields, 150kHz) Concomitant With Gemcitabine and Nab-paclitaxel for Front-line Treatment of Locally-advanced Pancreatic Adenocarcinoma
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 571
- 试验地点
- 199
- 主要终点
- Overall survival
研究概览
简要总结
Brief Summary:
The study is a prospective, randomized controlled phase III trial aimed to test the efficacy and safety of Tumor Treating Fields (TTFields) in combination with gemcitabine and nab-paclitaxel, for front line treatment of locally-advanced 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 (TTFields, TTF) has demonstrated significant activity in in vitro and in vivo pancreatic adenocarcinoma pre-clinical models both as a single modality treatment and in combination with chemotherapies. TTFields have been demonstrated to act synergistically with taxanes and have been shown to be additive when combined with other chemotherapies including gemcitabine. In addition, TTFields have shown to inhibit metastatic spread of malignant melanoma in in vivo experiment.
In a pilot study, 40 patients with locally advanced or metastatic pancreatic adenocarcinoma received gemcitabine together with TTFields (150 kHz) or gemcitabine and nab-paclitaxel together with TTFields (150 kHz) applied to the abdomen until disease progression. 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
- 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
- •18 years of age and older
- •Life expectancy of ≥ 3 months
- •Histological/cytological diagnosis of de novo adenocarcinoma of the pancreas
- •Unresectable, locally advanced stage disease according to the following criteria:
- •Head/uncinate process:
- •Solid tumor contact with SMA>180°
- •Solid tumor contact with the CA>180°
- •Solid tumor contact with the first jejunal SMA branch
- •Unreconstructible SMV/PV due to tumor involvement or occlusion (can be d/t tumor or bland thrombus)
- •Contact with most proximal draining jejunal branch into SMV
- •Body and tail
- •Solid tumor contact of >180° with the SMA or CA
- •Solid tumor contact with the CA and aortic involvement
- •Unreconstructible SMV/PV due to tumor involvement or occlusion (can be d/t tumor or bland thrombus)
- •No distant metastasis, including non-regional lymph node metastasis
- •No borderline resectable (per Al-Hawary MM, et al., Radiology 201414)
- •ECOG score 0-2
- •Amenable and assigned by the investigator to receive therapy with gemcitabine and nab-paclitaxel
- •Able to operate the NovoTTF-200T System independently or with the help of a caregiver
- •Signed informed consent form for the study protocol
排除标准
- •Prior palliative treatment (e.g. surgery, radiation) to the tumor
- •Cancer requiring anti-tumor treatment within the 5 years before inclusion, excluding treated stage I prostate cancer, in situ cervical or uterus cancer, in situ breast cancer and non-melanomatous skin cancer.
- •Serious co-morbidities:
- •Clinically significant (as determined by the investigator) hematological, hepatic and renal dysfunction, defined as: Neutrophil count < 1.5 x 10^9/L and platelet count < 100 x 10^9/L; bilirubin > 1.5 x Upper Limit of Normal (ULN); AST and/or ALT > 2.5 x ULN; and serum creatinine > 1.5 x ULN.
- •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.
- •History of cerebrovascular accident (CVA) within 6 months prior to randomization or that is not stable.
- •Active infection or serious underlying medical condition that would impair the ability of the patient to receive protocol therapy.
- •History of any psychiatric condition that might impair patient's ability to understand or comply with the requirements of the study or to provide consent.
- •Concurrent anti-tumor therapy beyond gemcitabine and nab-paclitaxel
- •Implantable electronic medical devices in the torso, such as pacemakers
- •Known severe hypersensitivities to medical adhesives or hydrogel, or to one of the chemotherapies used in this trial.
- •Pregnancy or breast-feeding (female patients with reproductive potential and their partners must accept to use effective contraception throughout the entire study period and for 3 months after the end of treatment). All patients who are capable of becoming pregnant must take a pregnancy test which is negative within 72 hours before beginning treatment. The definition of effective contraception is left up to the decision of the investigator.
- •Unable to follow the protocol for medical, psychological, familial, geographic or other reasons.
- •Admitted to an institution by administrative or court order.
研究组 & 干预措施
NovoTTF-200T
Patients receive TTFields using the NovoTTF-200T System together with gemcitabine and nab-Paclitaxel
干预措施: NovoTTF-200T (Device)
Best Standard of Care
Patients receive best standard of care with gemcitabine and nab-Paclitaxel
干预措施: nab paclitaxel (Drug)
NovoTTF-200T
Patients receive TTFields using the NovoTTF-200T System together with gemcitabine and nab-Paclitaxel
干预措施: Gemcitabine (Drug)
NovoTTF-200T
Patients receive TTFields using the NovoTTF-200T System together with gemcitabine and nab-Paclitaxel
干预措施: nab paclitaxel (Drug)
Best Standard of Care
Patients receive best standard of care with gemcitabine and nab-Paclitaxel
干预措施: Gemcitabine (Drug)
结局指标
主要结局
Overall survival
时间窗: 4 years
次要结局
- Progression-free survival(4 years)
- Puncture-free survival(4 years)
- Resectability rate(4 years)
- Local progression-free survival(4 years)
- Objective response rate(4 years)
- One-year survival rate(4 years)
- Quality of life(4 years)
- Pain-free survival(4 years)
- Toxicity profile(4 years)