Carboplatin, Pemetrexed with Cetuximab for Advanced Non-Small cell lung cancer with EGFR exon 20 insertion – A Multi-centric Prospective Phase II trial
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 20
- 试验地点
- 2
- 主要终点
- Objective Response Rates (ORR) following three months of planned systemic therapy assessed using RECIST v1.1 by a Thoracic Radiologist
研究概览
简要总结
Lung cancer poses a critical challenge globally due to its high incidence and frequent diagnosis at advanced stages. In non-small cell lung cancer (NSCLC), roughly 30% of cases have a specific genetic mutation called EGFR, with three main subtypes. The third most prevalent subtype, called EGFR exon 20 insertion (ex20ins), has a dismal prognosis and does not respond to conventional targeted therapies. While the global prevalence of ex20ins is estimated at up to 12%, limited data exists in developing countries that rely on traditional molecular tests, which often miss detecting this mutation, making accurate diagnosis difficult. Recently, with more widespread adoption of advanced molecular diagnostic tests like Next-Generation Sequencing (NGS), the true incidence of EGFR ex20ins in under-studied populations can be determined precisely, thus impacting treatment strategies. Currently, the standard treatment of EGFR ex20ins advanced NSCLC with the targeted agent ’Amivantamab’ combined with chemotherapy is often inaccessible in low- and middle-income countries due to its high cost. The majority of patients in these countries pay for treatment expenses from out-of-pocket, and realistically, they end up getting chemotherapy alone. However, chemotherapy alone offers poor outcomes, with low survival rates. We propose an affordable, globally more accessible, and potentially effective alternative: combining chemotherapy with the anti-EGFR monoclonal antibody Cetuximab. Early studies suggest promise for Cetuximab in EGFR ex20ins patients. Our research aims to confirm its safety and efficacy compared to chemotherapy alone. This approach could offer renewed hope and improved outcomes for countless patients struggling with limited treatment options if successful.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 盲法
- None
入排标准
- 年龄范围
- 18.00 Year(s) 至 80.00 Year(s)（—）
- 性别
- All
入选标准
- •Histologically or cytologically confirmed locally advanced or metastatic non-squamous NSCLC with EGFR exon 20 insertion mutation on tissue demonstrated by Next Generation Sequencing or Polymerase Chain Reaction
- •Measurable disease present according to RECIST v1.1
- •Adults more than 18 years of age with ECOG Performance status 0-1
- •Written informed consent obtained from the subject or the subject’s legal representative and the ability of the subject to comply with the requirements of the study.
- •Required initial laboratory parameters: Haemoglobin more than or equal to 10g/dl, Absolute neutrophil count more than 1500/microL,Platelets more than 1 lakh per microL, ALT and AST less than or equal to 3 times upper limit of normal (ULN), Total bilirubin less than or equal to 1.5 x ULN (participants with Gilbert’s syndrome can enroll if conjugated bilirubin is within normal limits), Creatinine clearance more than 50 mL/min by Cockroft -Gault formula.
排除标准
- •Any prior systemic treatment for locally advanced or metastatic lung cancer except for a.
- •Symptomatic Patients who received cycle one chemotherapy with carboplatin and pemetrexed while awaiting molecular results b.
- •Prior monotherapy with an approved EGFR TKI (gefitinib, erlotinib, afatinib, or Osimertinib) as non-standard first-line therapy for the treatment of locally advanced or metastatic disease is allowed if
- •treatment duration did not exceed eight weeks
- •lack of disease response was documented (radiographically) by an increase in tumor burden;
- •associated toxicities have resolved to baseline; and
- •the EGFR TKI has discontinued at least two weeks or four half-lives before enrolment, whichever is longer c.
- •Prior adjuvant or neoadjuvant platinum-based doublet chemotherapy is allowed if completed at least 12 months prior
- •Synchronous NSCLC with an EGFR mutation other than EGFR Exon 20ins.
- •Symptomatic, untreated brain metastases (a participant with definitively, locally treated metastases who is clinically stable, asymptomatic, and off corticosteroid treatment for at least two weeks before enrolment is eligible)
- •History of leptomeningeal disease or spinal cord compression
- •Active malignancy (i.e., progressing or requiring treatment change in the last 24 months) other than the disease being treated under study.
- •Pregnant, breastfeeding, or unwilling to practice birth control during participation.
- •Major surgical procedure within 28 days of enrolment or anticipation of the need for major surgery during study other than that required for the cancer treatment.
- •Diagnosis of deep vein thrombosis or pulmonary embolism within one month before or any of the following within six months prior: any acute coronary syndrome, stroke, transient ischemic attack, coronary/peripheral artery bypass graft b.
- •Prolonged corrected QT interval by Fridericia’s (QTcF) more than 480 msec, clinically significant cardiac arrhythmia, or electrophysiologic disease c.
- •Uncontrolled (persistent) hypertension: systolic blood pressure more than 160 mm Hg; diastolic blood pressure more than 100 mm Hg d.
- •Congestive heart failure is defined as New York Heart Association (NYHA) Class III/IV or hospitalization for congestive heart failure (any NYHA class) within the previous six months.
- •Myocarditis/Pericarditis/clinically significant pericardial effusion f.
- •Baseline left ventricular ejection fraction below the lower limit of normal as assessed by screening echocardiogram (ECHO) or multigated acquisition scan.
结局指标
主要结局
Objective Response Rates (ORR) following three months of planned systemic therapy assessed using RECIST v1.1 by a Thoracic Radiologist
时间窗: Baseline, 12 weeks
次要结局
- Assessment of the safety profile of the planned systemic therapy, with adverse grades as per Common Terminology Criteria for Adverse Events (CTCAE) v5.0(Baseline, 3 weeks, 6 weeks, 9 weeks, 12 weeks)
研究者
Ashish Singh
Christian Medical College, Vellore, India