A Phase II Double Blind Randomized Trial Comparing Standard Dosing Based on Body Surface Area Versus Dosing Based on Personalized Lean Body Mass in Patients With Stage IIIB or IV Non-Small Cell Lung Cancer Receiving First Line Cisplatin Based Chemotherapy
试验速览
- 阶段
- 2 期
- 入组人数
- 144
- 试验地点
- 2
- 主要终点
- Dose limiting toxicity rates
研究概览
简要总结
Cancer patients are highly variable in their body composition, specifically in the proportion of fat and muscle. Some patients tend to gain fat and lose muscle (or lean body mass) at the same time. These patients can develop severe muscle wasting, termed sarcopenia. Patients with sarcopenia have more severe treatment related toxicity requiring delays, dose reductions and stopping of treatment, and have reduced survival. One potential explanation for this is that patients with sarcopenia have a reduced volume of lean body mass into which chemotherapy drugs are distributed, resulting in a higher concentration and greater toxicity. This study will randomize lung cancer patients to either the standard dosing strategy based on body surface area or experimental, personalized dosing based on lean body mass. Based on retrospective findings in this patient population, the investigators expect to find that severe toxicity will be reduced for sarcopenic patients on the personalized dosing arm based on lean body mass.
详细描述
Retrospective findings of NSCLC patients treated with a cisplatin based chemotherapy regimen show that although all were given cisplatin at the standard rate of 75 mg/m2 according to lean body mass, when this was expressed in relation to individual lean body mass, there was a high degree of variation. Incidence of dose limiting toxicity was 41% in patients whose dose was within + 25% of the median value. However, sarcopenic patients received on average a 35% higher dose and 80% of these patients experienced severe toxicity requiring dose reduction or termination of therapy, a clinically unacceptable level. The relatively muscular subset of patients with higher lean body mass had a reduced level of severe toxicity compared to those at the median dose. These findings have led to the design of a study with the goal of reducing high levels of toxicity in sarcopenic patients. If the expected level of dose limiting toxicity in sarcopenic patients is 80% based on the standard method of dosing, this could be expected to be reduced to the median value of 41% dose limiting toxicity by the administration of cisplatin scaled to individual lean body mass. Hypothesis: Levels of severe toxicity in sarcopenic patients may be reduced to clinically acceptable levels by cisplatin dosing scaled to 3.1 mg/kg lean body mass compared with standard dosing of 75 mg/m2 based on body surface area.
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
- Double (Participant, 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
- •Recommendation from treating oncologist to receive a cisplatin based chemotherapy regimen, specifically either cisplatin/vinorelbine or cisplatin/gemcitabine
- •> or = 18 years of age
- •Histologically proven diagnosis of non-small cell lung cancer, Stage IIIB or IV
- •Adequate renal function: creatinine < 1.5 mg/dL or < 132 µmol/L and creatinine clearance of > 45 mL/min using the Cockcroft-Gault formula
- •Adequate hepatic function: bilirubin < 1.5 mg/dL or < 25 µmol/L and AST and ALT < 2 times upper limit of normal, unless there is evidence of liver metastases, in which case < 5 times upper limit of normal
- •Adequate hematological function: absolute neutrophil count (ANC) > 1.5 x 109/L and platelets > 100 x 109/L and hemoglobin > 100 g/L
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 - 2
- •Negative serum pregnancy test for women of childbearing potential. Women and men of child bearing potential must use effective contraception defined as the simultaneous use of two reliable methods unless abstinence is the chosen method.
- •Life expectancy of > 4 months in the opinion of the treating oncologist
- •Prior radiotherapy is allowed (unless > 25% of bone marrow stores) if this radiation was > 4 weeks before study entry and patient has fully recovered from toxicity of this treatment
- •Willingness to comply with the study protocol
- •Ability to give written informed consent with the understanding that it may be withdrawn at any time without prejudice
排除标准
- •Pregnant or lactating women
- •Brain metastases (a CT or MRI is not required to rule out brain metastases unless there is clinical suspicion)
- •Previous or concurrent malignancies, excluding curatively treated in situ carcinoma of the cervix, in situ ductal breast cancer, non-melanoma skin cancer or low grade bladder cancer
- •Patients who have had major surgery within three weeks of enrollment without a full recovery
- •Prior treatment with any anticancer therapy
- •Patients who have tested positive for HIV
- •Any significant medical or psychiatric condition that, in the opinion of the investigator, will exclude the patient from the study for compliance or safety reasons
结局指标
主要结局
Dose limiting toxicity rates
时间窗: Assessed weekly until patients come off study (an expected average of 9 weeks)
Number of Cycles completed
时间窗: Assessed weekly until patients come off study (an expected average of 9 weeks)
次要结局
- Survival(Assessed every 60 days from the date of removal from the trial (an expected average of 9 months))