LUNAR: Pivotal, Randomized, Open-label Study of Tumor Treating Fields (TTFields) Concurrent With Standard of Care Therapies for Treatment of Stage 4 Non-small Cell Lung Cancer (NSCLC) Following Platinum Failure
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 291
- 试验地点
- 124
- 主要终点
- Overall Survival of Patients Treated With TTFields + Docetaxel or Immune Checkpoint Inhibitors vs. Docetaxel or Immune Checkpoint Inhibitors Alone (Superiority Analysis)
研究概览
简要总结
The study is a prospective, randomized controlled phase III trial aimed to test the efficacy and safety of TTFields, using the NovoTTF-200T device, concurrent with standard therapies for stage 4 NSCLC patients, following progression while on or after platinum based treatment. 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 NSCLC pre-clinical models both as a single modality treatment and in combination with chemotherapies and PD-1 inhibitors. TTFields have been demonstrated to act synergistically with taxanes and have been shown to be additive when combined with PD-1 inhibitors. In addition, TTFields have shown to inhibit metastatic spread of malignant melanoma in in vivo experiment.
In a pilot study, 42 patients with advanced NSCLC who had had tumor progression after at least one line of prior chemotherapy, received pemetrexed together with TTFields (150 kHz) applied to the chest and upper abdomen until disease progression (Pless M., et al., Lung Cancer 2011). The combination was well tolerated and the only device-related adverse event was mild to moderate contact dermatitis. Efficacy endpoints were remarkably high compared to historical data for pemetrexed alone.
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 2015).
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
- 22 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •22 years of age and older (some regional variations to inclusion age exist)
- •Life expectancy of ≥ 3 months
- •Histological diagnosis of squamous or non-squamous, inoperable, metastatic NSCLC
- •Diagnosis of radiological progression while on or after first platinum-based systemic therapy administered for advanced or metastatic disease.
- •Patients who received adjuvant or neoadjuvant platinum-based chemotherapy (after surgery and/or radiation therapy) and developed metastatic disease within 6 months of completing therapy are eligible.
- •Patients with metastatic disease more than 6 months after adjuvant or neoadjuvant platinum-based chemotherapy, who also subsequently progressed during or after a platinum- based regimen given to treat the advanced or metastatic disease, are eligible.
- •Patients should not receive any systemic therapy after platinum failure before enrollment into the study. Maintenance therapy after platinum based therapy and prior to progression is allowed.
- •ECOG Score of 0-2
- •Assigned by the physician to receive either docetaxel or immune checkpoint inhibitor per standard of care regimen
- •Able to operate the NovoTTF-200T device independently or with the help of a caregiver
- •Signed informed consent for the study protocol
排除标准
- •Metastases to central nervous system (CNS) with clinical symptoms or evidence of new metastases to CNS during screening. Patients who previously received treatments for the metastases to CNS, are stable and meet the following requirements are allowed to be enrolled:
- •The patients are neurologically returned to baseline (except for residual signs or symptoms related to CNS treatment).
- •No treatment for the metastases to CNS during the screening period (e.g. surgery, radiotherapy, corticosteroid therapy- prednisone > 10 mg/day or equivalent).
- •No progress in CNS lesions as indicated by MRI within 14 days prior to randomization.
- •No meningeal metastasis or spinal cord compression.
- •Patients planned to receive immune checkpoint inhibitor with contra-indications to receive immunotherapy
- •Patients planned to receive docetaxel with contra-indications to receive docetaxel
- •Severe comorbidities:
- •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 ULN; AST and/or ALT > 2.5 x ULN or > 5 x ULN if patient has documented liver metastases; 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 pericarditis
- •History of interstitial lung disease
- •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 received 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
- •Any other malignancy requiring anti-tumor treatment in the past three years, excluding treated stage I prostate cancer, in situ cervical cancer, in situ breast cancer and non-melanomatous skin cancer
- •Concurrent treatment with other experimental treatments for NSCLC while on the study
- •Implantable electronic medical devices (e.g. pacemaker, defibrillator) in the upper torso
- •Known allergies to medical adhesives or hydrogel
- •Pregnancy or breast-feeding (patients with reproductive potential must use effective contraception methods throughout the entire study period, as determined by their investigator/gynecologist)
- •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 device together with immune checkpoint inhibitors or docetaxel
干预措施: NovoTTF-200T (Device)
NovoTTF-200T
Patients receive TTFields using the NovoTTF-200T device together with immune checkpoint inhibitors or docetaxel
干预措施: Immune checkpoint inhibitors or docetaxel (Drug)
Best Standard of Care
Patients receive best standard of care with immune checkpoint inhibitors or docetaxel
干预措施: Immune checkpoint inhibitors or docetaxel (Drug)
结局指标
主要结局
Overall Survival of Patients Treated With TTFields + Docetaxel or Immune Checkpoint Inhibitors vs. Docetaxel or Immune Checkpoint Inhibitors Alone (Superiority Analysis)
时间窗: From date of randomization until the date of death from any cause, assessed up to 12 month after the last participant was enrolled (median duration of follow-up was 10.0 months).
次要结局
- Overall Survival of Patients Treated With TTFields + Immune Checkpoint Inhibitors vs. Immune Checkpoint Inhibitors Alone (Superiority)(From date of randomization until the date of death from any cause, assessed up to 12 month after the last participant was enrolled (median duration of follow-up was 10.6 months).)
- Overall Survival of Patients Treated With TTFields + Docetaxel vs. Docetaxel Alone (Superiority Analysis)(From date of randomization until the date of death from any cause, assessed up to 12 month after the last participant was enrolled (median duration of follow-up was 9.7 months).)
- Overall Survival of Patients Treated With TTFields + Docetaxel Vs. Immune Checkpoint Inhibitors Alone (Non-inferiority Analysis)(From date of randomization until the date of death from any cause, assessed up to 12 month after the last participant was enrolled. (median duration of follow-up was 10.1 months))
- Progression-free Survival of Patients Treated With Docetaxel or Immune Checkpoint Inhibitors + TTFields vs. Docetaxel or Immune Checkpoint Inhibitors Alone, Based on RECIST Criteria(From date of randomization until the date of disease progression according to RECIST criteria, assessed up to 12 month after the last participant was enrolled (median duration of follow-up was 10.0 months, maximal follow-up duration was 64.4 months).)
- Overall Radiological Response Rate (Based on RECIST Criteria) of Patients Treated With Docetaxel or Immune Checkpoint Inhibitors + TTFields vs. Docetaxel or Immune Checkpoint Inhibitors Alone.(From date of randomization until the date of disease progression according to RECIST criteria, assessed up to 12 month after the last participant was enrolled (median duration of follow-up was 4.2 months, maximal follow-up duration was 64.4 months).)
- Quality of Life Using the EORTC QLQ C30 Questionnaire With LC13 Addendum(From baseline up to 54 weeks)
- Analyses of the Effects of NovoTTF-200T With Each Type of Immune Checkpoint Inhibitor on Overall Survival and Progression Free Survival(From date of randomization until the date of death from any cause (OS), or until date of disease progression according to RECIST criteria (PFS) , assessed up to 12 month after last participant enrolled (median duration of follow-up 10.7 months).)
- Analysis of the Effects of NovoTTF-200T on Overall Survival and Progression Free Survival Within Each Histological Subgroup (Squamous and Non-squamous)(From date of randomization until the date of death from any cause (OS), or until date of disease progression according to RECIST criteria (PFS) , assessed up to 12 month after last participant enrolled (median duration of follow-up 10.0 months).)
- The Effect of Treatment Compliance With NovoTTF-200T on Overall Survival and Progression Free Survival Outcomes(From date of randomization until the date of death from any cause (OS), or until date of disease progression according to RECIST criteria (PFS) , assessed up to 12 month after last participant enrolled (median duration of follow-up 10.7 months).)
- Adverse Events, Severity and Frequency Based on Common Terminology Criteria for Adverse Events (CTCAE) V4.03(From date of randomization until the date of death from any cause, or study completion (up to 100 days following treatment termination, maximal follow-up duration was 55.8 months).)