Optimum Duration of Vitamin B12 and Folate Supplementation in Non-squamous Non-small Cell Lung Cancer (NSCLC) Patients Undergoing Pemetrexed Containing Chemotherapy: a Randomized Controlled Trial
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 161
- 试验地点
- 1
- 主要终点
- Incidence of any grade hematological toxicity
研究概览
简要总结
Folic acid (FA; folate) in the dose of 350-1,000 μg daily should be supplemented, daily, starting 7 days before the first dose of pemetrexed based chemotherapy and should be continued while the patient is on therapy and for 21 days after cessation of therapy. Vitamin B12 injections (1,000 μg i.m.) should also be started 1 week before the first dose of chemotherapy. However, the evidence for delaying chemotherapy by seven days for the purpose of giving vitamin B12 and FA supplementation is not robust. Observational and prospective single arm studies have not shown any increased toxicity if pemetrexed was started earlier than the recommended duration of supplementation. In a resource constrained setting, this will lead to one additional visit and 1-week chemotherapy delay which may be inconvenient for patients.
Hence an open label, randomized control trial is being undertaken to evaluate if there are any differences in pemetrexed related hematological toxicity amongst patients who receive delayed initiation of chemotherapy (following 5 - 7 days of vitamin B12 and FA supplementation; Delayed Arm) as compared to those in whom vitamin B12 and FA supplementation is starting simultaneously (within 24 hours) of initiation of chemotherapy (Immediate Arm).
详细描述
Chemotherapy Regimen:
All patients will receive pemetrexed and cisplatin in doses of 500 mg and 65 mg, respectively, per square meter of body surface area each on day 1 of a 3-week cycle. Patients with contraindications to administration of cisplatin, those who are intolerant to cisplatin, or develop grade 3 or 4 adverse events from cisplatin will be given carboplatin in combination with pemetrexed. Carboplatin will be given at a dose calculated to produce an area under the concentration-time curve (AUC) of 5.0mg/mL/min. Dose modifications of either pemetrexed or the platinum agent or both will be done in case of significant change in PS or toxicity from or intolerance to dose administered in the previous cycle.
Supplementation:
- Folic acid (FA) supplementation will be given to all patients orally in the dose of 5 ml (1000 μg) once daily of VITCOFOL (FDC Limited, Mumbai, India) pediatric formulation, which contains 200 μg FA/ml of the preparation. Patients will be instructed to measure the prescribed dose using a 5 ml plastic syringe containing markings at every 0.5 ml. Patients will also be instructed not to take any additional multivitamin supplements. In addition to FA supplementation, all patients will also be started simultaneously on oral iron (ferrous sulphate 200 mg twice a day). Once initiated, both FA and ferrous sulphate will be given on a daily basis and continued throughout the duration of chemotherapy and for at least 3 weeks beyond the last cycle.
- Vitamin B12 supplementation will be given to all patients intramuscularly in the dose of 1000 μg along with each cycle of chemotherapy (maximum of six doses during the study period).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 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
- •Locally advanced or metastatic (Stage IIIB/IV) NSCLC and Stage III A NSCLC, not scheduled for upfront surgical resection
- •Nonsquamous histology (including adenocarcinoma)
- •At least one unidimensionally measurable lesion, according to the Response Evaluation Criteria in Solid Tumors (RECIST, version 1.0), or at least one nonmeasurable lesion that was assessable using conventional techniques or a spiral computed tomography scan
- •An Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
- •No previous chemotherapy for advanced disease and no previous targeted molecular therapy
- •Adequate liver and renal function;
- •Previous radiation therapy is permitted if completed >4 weeks before enrollment and the patient has recovered from any treatment-related toxicity.
排除标准
- •Hemoglobin value < 9gm/dl
- •Required erythropoiesis stimulating agents or blood transfusions in the recent past (4 months)
- •Symptomatic untreated brain metastasis
- •Any previous malignancy
- •Concurrent use of any other tumor therapy
- •Active infection or a serious concomitant disorder
- •Inability to interrupt nonsteroidal anti-inflammatory agents
- •Inability or unwillingness to take folic acid, vitamin B12, or dexamethasone supplementation
- •Pregnancy or breast feeding
研究组 & 干预措施
Delayed Arm
Participants are started on folate and vitamin B12 supplementation for 5-7 days prior to initiation of chemotherapy
Immediate Arm
Participants are started on folate and vitamin B12 supplementation simultaneously with chemotherapy (within 24 hours of initiation of chemotherapy)
干预措施: Folate and B12 (Dietary Supplement)
结局指标
主要结局
Incidence of any grade hematological toxicity
时间窗: Completion of six cycles (average of 18 weeks; each cycle is 21 days) of pemetrexed-platinum doublet chemotherapy
Incidence of Grade 1-5 Anemia, Grade 1-5 Neutropenia, Grade 1-5 Thrombocytopenia (all graded according to NCI CTCAE Version 3.0) related to pemetrexed-platinum doublet chemotherapy during the study period
次要结局
- Number of PRBC transfusions administered(Completion of six cycles (average of 18 weeks; each cycle is 21 days) of pemetrexed-platinum doublet chemotherapy)
- Relative Dose Intensity (RDI) delivered(Completion of six cycles (average of 18 weeks; each cycle is 21 days) of pemetrexed-platinum doublet chemotherapy)
- Incidence of grade 3/4 hematological toxicity(Completion of six cycles (average of 18 weeks; each cycle is 21 days) of pemetrexed-platinum doublet chemotherapy)
- Number of doses of G-CSF administered(Completion of six cycles (average of 18 weeks; each cycle is 21 days) of pemetrexed-platinum doublet chemotherapy)
- Number of doses of ESAs administered(Completion of six cycles (average of 18 weeks; each cycle is 21 days) of pemetrexed-platinum doublet chemotherapy)
- Number of Inter-Cycle Delays (ICDs)(Completion of six cycles (average of 18 weeks; each cycle is 21 days) of pemetrexed-platinum doublet chemotherapy)
研究者
Dr. Navneet Singh
Associate Professor
Post Graduate Institute of Medical Education and Research, Chandigarh