Oral L-arginine Supplementation in Patients With Non-resectable Brain Metastases Treated With Radiation Therapy With Palliative Intent
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 70
- 主要终点
- Change from baseline of the scoring form NCI CTCAE v3 for detecting and quantifying potential adverse events
研究概览
简要总结
This study evaluates the nutritional supplement arginine as supportive measure for patients with unresectable metastatic brain tumors that receive radiation therapy with palliative intent
详细描述
Brain metastasis, the most common intracranial tumor, is associated with neurological disability and short survival time. For selected patients this outcome can be improved by achieving greater local control. Virtually all cancer patients with brain metastases receive radiotherapy; a majority as part of their primary treatment while others in connection with surgery or palliation. Agents that increase the sensitivity of cancer cells to radiation may improve the control of the disease. Previous data indicates that arginine supplementation can modify the metabolism of cancer and immune cells making tumors more susceptible to standard treatments liked radiation. In this phase 1/2 comparative study the investigators will investigate whether 10 mg of arginine oral supplementation (compared to placebo administration) administered twice a day prior to the radiation therapy can modify tumor metabolism, immune response and effect of radiation. The primary end-points are safety and toxicity of arginine, quality-of-life and clinical response. The secondary end-points are imaging response and neurological progression-free survival. Additional exploratory end-points include intensity of radiation administered, effects on tumor metabolism by magnetic resonance spectroscopy, immune response by cytokine pattern in serum, body composition and nutritional parameters , overall survival and progression free survival
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Supportive Care
- 盲法
- Triple (Participant, Care Provider, Investigator)
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 pathology-confirmed diagnostic of solid cancer and measurable brain metastases by CT scan and/or MRI
- •Inclusion Criteria:
- •Unresectable criteria by neurosurgeon
- •Recursive partitioning analysis (RPA) -Radiation Therapy Oncology Group (RTOG) class II (Karnofsky's performance score ≥ 70 and extracranial metastases and/or non-controlled primary tumor)
- •Measurable brain lesion/s by contrast-enhanced CT or MRI
- •Absolute granulocyte count more or equal than 2000/mm3
- •Hemoglobin more or equal than 9 g/L (patients with lower levels were transfused before the randomization)
- •Normal renal laboratory (serum creatinine <1.5 mg/dL and 24-h creatinine clearance >60 mL/min)
- •Normal hepatic function (aspartate aminotransferase and alanine aminotransferase <2.5 times the upper limit of normal)
- •Stable body weight and composition for at least one month prior enrollment
排除标准
- •Prior treatment for brain metastases and/or brain tumor.
- •Primary brain tumor
- •Hematologic malignancies
- •Solid tumors of germinal origin
- •Contraindication for external radiation therapy.
- •Allergy to L-arginine.
结局指标
主要结局
Change from baseline of the scoring form NCI CTCAE v3 for detecting and quantifying potential adverse events
时间窗: Baseline and thereafter every 7 days starting from day 1 of L-arginine or placebo administration and through study completion, an average of 1 year
NCI CTCAE v3 form will be completed baseline and every 7 days starting from day 1 of L-arginine or placebo administration thereafter. This form will detect adverse events including clinical laboratory alterations associated with the administration of of L-arginine or placebo including those that may exacerbate the adverse events expected from the radiation therapy
Change from baseline in signs and symptoms of neurological disease
时间窗: Baseline and at 4 weeks counted from the last day of treatment
Signs and symptoms of neurological disease will be evaluated by caregiver and investigator according to response criteria evaluation guidelines. Clinical response will be considered as the changes in signs and symptoms that occur between baseline state and 30 days counted from the last day of treatment
Change from baseline of quality of life questionnaire
时间窗: Baseline and thereafter every 7 days starting from day 1 of L-arginine or placebo administration and through study completion, an average of 1 year
Quality of life questionnaire with assessment of the Karnofsky's index will be completed baseline and every 7 days starting from day 1 of L-arginine or placebo administration thereafter
次要结局
- Neurological progression-free survival(Time with no radiological or symptomatic progression counted from the first of radiation therapy until the day of first documented neurological progression or date of death from any cause, whichever came first, assessed up to 50 months)
- Imaging response(One month after the last day of radiation and one month after the first response assessment)