Open-label, Multicenter, Randomized Phase II Trial of Treatment With Cisplatin and Pemetrexed or Cisplatin and Oral Vinorelbine in Chemotherapy Naïve Patients Affected by Stage IIIB-IV Non-Squamous Non-Small Cell Lung Cancer With High Thymidylate Synthase Expression
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 2
- 试验地点
- 5
- 主要终点
- Disease Control Rate (DCR)
研究概览
简要总结
This is an open-label, multicentre, randomized phase II trial.
Eligible patients with Non Small Cell Lung Cancer (NSCLC) with high Thymidylate Synthase (TS) expression , will be randomly assigned with 1:1 ratio to the following treatment Arms:
A. 4 cycles of Cisplatin + Oral Vinorelbine followed by maintenance with Metronomic Oral Vinorelbine until disease progression
B. 4 cycles of Cisplatin + Pemetrexed followed by maintenance with Pemetrexed until disease progression
Treatment will be repeated every 21 days .
详细描述
An Open-label, Multicenter, Randomized Phase II Trial of Treatment with Cisplatin and Pemetrexed or Cisplatin and Oral Vinorelbine in Chemotherapy Naïve Patients affected by stage IIIB-IV Non-Squamous Non-Small Cell Lung Cancer with high Thymidylate Synthase (TS)expression After signing the informed consent for TS expression evaluation (see Appendix A), patients will be tested for TS expression status of their tumor tissue.
If TS expression is more than 70 in the nucleus or ≥210 in nucleus and in the cytoplasm of tumor cell, they will be categorized as high TS expression patients, and if it is less, they will be considered as TS-negative.
Study Treatment:
Eligible patients will be randomly assigned to the following treatment Arms:
A. Oral vinorelbine 60-80 mg/m2 on days 1 and 8 (first cycle 60 mg/m2) + Cisplatin 80 mg/m2 on day 1 every 3 weeks, for 4 cycles.
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
- •Patients must have histologically or cytologically Non-squamous NSCLC, (including those with a non-specified tumor type).
- •Metastatic (stage IV, both M1A or M1B) or locally advanced (stage IIIB, with metastasis to supraclavicular nodes) according to TNM VII edition.
- •TS nuclear H-score ≥ 70 or with TS nuclear and cytoplasmatic H-score ≥
- •Patients at first diagnosis or those with disease recurrence after former surgery are eligible.
- •Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as ≥20 mm with conventional techniques or as ≥10 mm with spiral CT scan. See section 9.2 and Appendix E for the evaluation of measurable disease.
- •At least one target or non-target lesion not previously irradiated according to RECIST version 1.1
- •Male or Female, aged ≥18 years.
- •Life expectancy greater than 3 months.
- •ECOG performance status ≤2 (see Appendix C).
- •Patients must have normal organ and marrow function as defined below:
- •leukocytes ≥3,000/µL
- •absolute neutrophil count ≥1,000µL
- •platelets ≥100,000/µL
- •total bilirubin within normal institutional limits
- •AST(SGOT)/ALT(SGPT) ≤2.5 X institutional upper limit of normal
- •creatinine within normal institutional limits OR
- •creatinine clearance ≥60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal
- •Female participants of child bearing potential and male participants whose partner is of child bearing potential must be willing to ensure that they or their partner use effective contraception during the study and for 3 months thereafter
- •Participant is willing and able to give informed consent for participation in the study.
排除标准
- •Prior chemotherapy or therapy with systemic anti-neoplastic therapy for advanced disease.
- •Prior surgery and/or localised irradiation is permitted if delivered outside to the target lesion.
- •Prior adjuvant chemotherapy is permitted if it did not contain vinorelbine and pemetrexed and if administered at least 6 months prior entering the study.
- •Participation in another clinical trial with any investigational agents within 30 days prior to study screening.
- •Patients with symptomatic brain metastasis or spinal cord compression that has not yet been treated with surgery and/or radiation. Patients with CNS metastases or spinal cord compression previously treated with surgery and/or radiation are eligible if they are asymptomatic and do not require escalating high dose steroids (anti-seizure medications are allowed)
- •History of allergic reactions attributed to compounds of similar chemical or biologic composition to pemetrexed, vinorelbine, cisplatin, carboplatin or other agents used in the study.
- •Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- •Other known malignant neoplastic diseases in the patient's medical history with a disease-free interval of less than 5 years (except for previously treated basal cell carcinoma and in situ carcinoma of the uterine cervix or surgically resected prostate cancer with normal PSA);
- •NSCLC with EGFR mutation (or not able to use EGFR inhibitor) or with anaplastic lymphoma kinase (ALK) gene translocation (such as EML4-ALK).
- •Has a known allergy, hypersensitivity, or contraindication to cisplatin, pemetrexed, or vinorelbine or any components used in their preparation or has a contraindication specified in section 7.
研究组 & 干预措施
Treatment Arm A
Oral vinorelbine 60-80 mg/m2 on days 1 and 8 (first cycle 60 mg/m2) + Cisplatin 80 mg/m2 on day 1 every 3 weeks, for 4 cycles.
Maintenance with Metronomic Oral Vinorelbine 50 mg three times a week on Monday, Wednesday and Friday continuously until disease progression, patient refusal or excessive toxicity (1 cycle: 3 weeks).
干预措施: Oral vinorelbine (Drug)
Treatment Arm A
Oral vinorelbine 60-80 mg/m2 on days 1 and 8 (first cycle 60 mg/m2) + Cisplatin 80 mg/m2 on day 1 every 3 weeks, for 4 cycles.
Maintenance with Metronomic Oral Vinorelbine 50 mg three times a week on Monday, Wednesday and Friday continuously until disease progression, patient refusal or excessive toxicity (1 cycle: 3 weeks).
干预措施: Cisplatin (Drug)
Treatment Arm A
Oral vinorelbine 60-80 mg/m2 on days 1 and 8 (first cycle 60 mg/m2) + Cisplatin 80 mg/m2 on day 1 every 3 weeks, for 4 cycles.
Maintenance with Metronomic Oral Vinorelbine 50 mg three times a week on Monday, Wednesday and Friday continuously until disease progression, patient refusal or excessive toxicity (1 cycle: 3 weeks).
干预措施: Maintenance with Metronomic Oral Vinorelbine (Drug)
Treatment Arm B
Pemetrexed, 500 mg/m2, day 1 + Cisplatin, 75 mg/m2, day 1 every 3 weeks, for 4 cycles.
Maintenance with Pemetrexed 500 mg/m2 day1 q 21 until disease progression (1 cycle: 3 weeks).
7-10 days before treatment administration, premedication with vitamin B12 1000µg intramuscular injection (every 9 weeks) and folate 1mg every day should be commenced.
干预措施: Pemetrexed (Drug)
Treatment Arm B
Pemetrexed, 500 mg/m2, day 1 + Cisplatin, 75 mg/m2, day 1 every 3 weeks, for 4 cycles.
Maintenance with Pemetrexed 500 mg/m2 day1 q 21 until disease progression (1 cycle: 3 weeks).
7-10 days before treatment administration, premedication with vitamin B12 1000µg intramuscular injection (every 9 weeks) and folate 1mg every day should be commenced.
干预措施: Cisplatin (Drug)
Treatment Arm B
Pemetrexed, 500 mg/m2, day 1 + Cisplatin, 75 mg/m2, day 1 every 3 weeks, for 4 cycles.
Maintenance with Pemetrexed 500 mg/m2 day1 q 21 until disease progression (1 cycle: 3 weeks).
7-10 days before treatment administration, premedication with vitamin B12 1000µg intramuscular injection (every 9 weeks) and folate 1mg every day should be commenced.
干预措施: Maintenance with Pemetrexed (Drug)
结局指标
主要结局
Disease Control Rate (DCR)
时间窗: up to 36 months
Rate (DCR; complete response (CR) plus partial response (PR) plus stable disease (SD)). The response is assessed according to the RECIST 1.1 criteria.
次要结局
- Overall survival (OS) within th 2 arms(up to 36 months)
- Progression free survival (PFS) within the two arms(up to 36 months)
- optimal TS H-score cutpoint(up to 36 months)
- Toxicity(up to 36 months)