Induction Therapy With Gefitinib Followed by Taxane Platinum Chemotherapy and Intercalated Gefitinib in NSCLC Stages II-IIIB With Activating EGFR Mutation - A Single Arm Phase II Trial.
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 1
- 试验地点
- 1
- 主要终点
- pathologic complete remission rate (pCR rate)
研究概览
简要总结
This study is designed as a single arm, un-controlled, open-label, multi-center hypothesis generating two-stage phase II trial. It is based on the assumption that the proposed treatment scheme doubles the rate of pathologic complete remission in Mutated epidermal growth factor receptor (EGFRmt) + NSCLC patients compared to historical control data from standard treatments.
Patients with NSCLC and activating EGFR mutation in stages II, IIIA and IIIB eligible for induction therapy with docetaxel and cisplatin and gefitinib
Patients will be treated for 12 days with gefitinib 250 mg/day p.o. (d -12 to -1) and induced with chemotherapy docetaxel 75 mg/m2 and cisplatin 50 mg/m2 d1+2 and intercalated gefitinib 250 mg/day d4-20 (cycle 1 and 2) and d4-17 (for cycle3). Surgery is planned in the 4th week after d1 of the last cycle.
详细描述
Based on the notion that neoadjuvant combination of Chemotherapy (CTx) and intercalated TKI is clinically beneficial, which can be inferred from prior study data and single case reports, this study aims to generate additional information on feasibility, safety and efficacy of this treatment approach in a larger group of EGFR mutated NSCLC patients. This study is a hypothesis generating two-stage trial for future phase III studies of neoadjuvant CTx with intercalated TKI. Hence, the study design relies entirely on a single treatment arm. To demonstrate efficacy it is sufficient to compare to historical data of the conventional treatments of NSCLC.
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
- •Patients with histologically or cytologically confirmed non-squamous non-small-cell lung cancer (NSCLC) stage II, IIIA and IIIB detected preoperatively by adequate methods and activating EGFR mutation in exons 18-21 and deemed to be able to undergo curative surgery after induction therapy. Stage should be confirmed by PET-CT as well as adequate mediastinal staging. MRI of the brain to exclude CNS metastases is mandatory.
- •At least one unidimensionally measurable lesion meeting RECIST criteria (version 1.1);
- •Performance status of 0 to 1 on the ECOG scale;
- •Estimated life expectancy of at least 12 weeks;
- •Patients aged ≥ 18 years;
- •Adequate organ function including the following:
- •Adequate bone marrow reserve:
- •absolute neutrophils (segmented and bands) count (ANC) ≥1.5x109/L;
- •platelets ≥100x109/L;
- •haemoglobin ≥9 g/dL.
- •bilirubin ≤ 1xULN;
- •alkaline phosphatase (AP);
- •aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 2.5xULN.
- •serum creatinine ≤ 1.3 mg/dL
- •glomerular filtration rate (GFR) ≥ 70 mL/min for cisplatinum based CTx;
- •If contraindications including GFR below 70mL/minagainst cisplatin exist, carboplatin may also be used;
- •glomerular filtration rate ≥ 30 mL/min (calculated) if carboplatin is to be used
- •Adequate lung function tests as assessed by body plethysmography, diffusion test and if necessary spiro-ergometry.
- •Cooperation and willingness to complete all aspects of the study;
- •Written informed consent to participate in the study.
排除标准
- •EGFR wild type configuration;
- •EGFR resistance mutations (i.e. T790M);
- •Significant cardiovascular disease, such as uncontrolled hypertension, myocardial infarction within the last 6 months, unstable angina pectoris, CHF ≥ NYHA 2, serious arrhythmia, significant peripheral vascular disease;
- •Pre-existing neuropathic ≥ grade 2;
- •Patients with confirmed HIV infection. HIV testing is not mandatory.
- •Prior history of malignancy except for basal cell carcinoma or carcinoma in situ of the cervix, and with the exception of other malignancies after curative treatment with an interval of at least 3 years.
- •Lactating or pregnant woman, woman of child-bearing potential who do not agree to the usage of highly effective contraception methods (allowed methods of contraception, meaning methods with a rate of failure of less than 1% per year are implants, injectable contraceptives, combined oral contraceptives, intrauterine devices (only hormonal devices), sexual abstinence or vasectomy of the partner). Woman of childbearing potential must have a negative pregnancy test (serum β-HCG) at visit
- •Any other chemotherapy at start;
- •Treatment with other experimental drugs during the course of the study or within the last 30 days or 7 half-lifes, whatever is of longer duration, prior study start;
- •Any psychiatric illness that would affect the patient's ability to understand the demands of the clinical trial;
- •Parallel participation in another clinical trial or participation in another clinical trial within the last 30 days or 7 half-lifes, whatever is of longer duration, prior study start;
- •Patient has already been included in this trial;
- •Patients who do not understand the nature, the scope and the consequences of the clinical trial;
- •Affected persons who might be dependent on the sponsor or the investigator.
研究组 & 干预措施
Treatment phase
Enrolled patients will be treated with 250mg/day Gefitinib for 11 days (day -12 until day -1) followed by 3 cycles (length 21 days) of chemotherapy with docetaxel (75mg/m2 d1) and cisplatin (50 mg/m2 d1+2) combined with intercalated gefitinib (250mg/day, d4-20 (cycle 1 and 2) and d4-17 (for cycle3). Surgery is planned in the 4th week after d1 of the last cycle.
干预措施: Gefitinib (Drug)
Treatment phase
Enrolled patients will be treated with 250mg/day Gefitinib for 11 days (day -12 until day -1) followed by 3 cycles (length 21 days) of chemotherapy with docetaxel (75mg/m2 d1) and cisplatin (50 mg/m2 d1+2) combined with intercalated gefitinib (250mg/day, d4-20 (cycle 1 and 2) and d4-17 (for cycle3). Surgery is planned in the 4th week after d1 of the last cycle.
干预措施: docetaxel (Drug)
Treatment phase
Enrolled patients will be treated with 250mg/day Gefitinib for 11 days (day -12 until day -1) followed by 3 cycles (length 21 days) of chemotherapy with docetaxel (75mg/m2 d1) and cisplatin (50 mg/m2 d1+2) combined with intercalated gefitinib (250mg/day, d4-20 (cycle 1 and 2) and d4-17 (for cycle3). Surgery is planned in the 4th week after d1 of the last cycle.
干预措施: cisplatin (Drug)
Treatment phase
Enrolled patients will be treated with 250mg/day Gefitinib for 11 days (day -12 until day -1) followed by 3 cycles (length 21 days) of chemotherapy with docetaxel (75mg/m2 d1) and cisplatin (50 mg/m2 d1+2) combined with intercalated gefitinib (250mg/day, d4-20 (cycle 1 and 2) and d4-17 (for cycle3). Surgery is planned in the 4th week after d1 of the last cycle.
干预措施: Surgery (Procedure)
结局指标
主要结局
pathologic complete remission rate (pCR rate)
时间窗: 12 weeks (after 3 cycles and surgery) after enrollment
The primary objective of the study is to assess the pathologic complete remission rate after induction therapy with gefitinib d -12 to d-1 followed by docetaxel 75 mg/m2 and cisplatin 50 mg/m2 d1+2 q21 and intercalated gefitinib 250 mg d4 to d20 (cycle 1 and 2) and d4-17 (for cycle3), in order to demonstrate feasibility and efficacy of this treatment scheme. It is expected to achieve a pCR ≥30% regression grade IIB and III (Junker criteria) compared to historical controls in the mediastinal lymph nodes.
次要结局
- Response: radiologic response based on CT(30 month)
- Adverse Events (AEs) / Serious adverse events (SAEs)(30 months)
- Surgical R0 resection rate(30 month)
- progression free survival (PFS)(30 month)
- Overall survival (OS)(30 month)
- quality of life(30 month)
- monitoring of epidermal growth factor receptor (EGFR) mutation status(30 month)
- relapse pattern(30 month)
- translational research(30 month)