Phase I/II Study of Two Different Schedules of Bortezomib (VELCADE, PS-341) and Pemetrexed (ALIMTA) in Advanced Solid Tumors, With Emphasis on Non-Small Cell Lung Cancer (NSCLC)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 27
- 试验地点
- 1
- 主要终点
- Number of Patients With Grade ≥ 3 Toxicity (Phase I)
研究概览
简要总结
RATIONALE: Bortezomib and pemetrexed disodium may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving bortezomib together with pemetrexed disodium may kill more tumor cells.
PURPOSE: This phase I/II trial is studying the side effects and best dose of two different schedules of bortezomib when given together with pemetrexed disodium and to see how well they work in treating patients with advanced non-small cell lung cancer or other solid tumors.
详细描述
OBJECTIVES:
Primary
- Determine the safety, including dose-limiting toxicities, and feasibility of combining bortezomib with pemetrexed disodium in patients with advanced non-small cell lung cancer (NSCLC) or other solid tumors. (Phase I)
- Determine the response rate in patients with advanced NSCLC treated with this regimen. (Phase II)
Secondary
- Compare the toxicity of 2 different schedules of bortezomib and pemetrexed disodium in patients with advanced solid tumors. (Phase I)
- Determine the maximum tolerated dose (MTD) of bortezomib when administered with pemetrexed disodium in 2 different treatment schedules in these patients. (Phase I)
- Determine, preliminarily, the efficacy of the combination of bortezomib and pemetrexed disodium in patients with advanced solid tumors. (Phase I)
- Assess the overall survival and progression-free survival of these patients. (Phase II)
- Evaluate the frequency and severity of toxicities associated with this regimen. (Phase II)
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 120 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •DISEASE CHARACTERISTICS:
- •Cytologically or histologically confirmed diagnosis of 1 of the following:
- •Advanced solid tumor that progressed after standard therapy or for which no effective curative therapy exists (phase I)
- •Stage IIIB (pleural effusion) or IV non-small cell lung cancer (NSCLC) (phase II)
- •Disease must have progressed or recurred after 1 platinum-based therapy regimen
- •NSCLC that has progressed or recurred after first-line therapy for stage IIIA or IIIB disease allowed
- •Measurable disease
- •Disease in previously irradiated sites is considered measurable if there is clear disease progression following radiotherapy
- •Evaluable disease (bone metastases, pleural fluid, ascites) allowed (phase I)
- •No symptomatic brain metastasis or disease requiring steroids and anticonvulsants
- •Asymptomatic, previously treated (surgical resection or radiotherapy) brain metastases allowed provided patient is neurologically stable and has been off steroids and anticonvulsants for ≥ 4 weeks
- •PATIENT CHARACTERISTICS:
- •Zubrod performance status 0-2 (phase I) or 0-1 (phase II)
- •Life expectancy ≥ 3 months
- •Creatinine ≤ 1.5 mg/dL OR creatinine clearance ≥ 50 mL/min
- •Bilirubin normal
- •AST ≤ 2.5 times upper limit of normal
- •Granulocyte count ≥ 1,500/mm³
- •Platelet count of ≥ 100,000/mm³
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective contraception during and for 3 months after completion of study treatment
- •No pre-existing neuropathy ≥ grade 2
- •No other prior malignancy except for the following (phase II):
- •Adequately treated basal cell or squamous cell skin cancer
- •In situ cervical cancer
- •Adequately treated stage I or II cancer currently in complete remission
- •Any other cancer from which the patient has been disease free for > 5 years
- •No hypersensitivity to bortezomib, boron, or mannitol
- •No cardiovascular complications, including any of the following:
- •Myocardial infarction within the past 6 months
- •New York Heart Association class III-IV heart failure
- •Uncontrolled angina
- •Severe uncontrolled ventricular arrhythmias
- •Electrocardiographic (ECG) evidence of acute ischemia or active conduction system abnormalities
- •Any ECG abnormality at screening must be documented as not medically relevant
- •PRIOR CONCURRENT THERAPY:
- •See Disease Characteristics
- •No prior bortezomib or pemetrexed disodium
- •Any number of prior chemotherapy regimens allowed (phase I)
- •More than 4 weeks since prior chemotherapy (6 weeks for mitomycin C) and recovered
- •More than 2 weeks since prior radiotherapy and recovered
- •No nonsteroidal anti-inflammatory drugs (NSAIDs) or salicylates 2 days prior and 2 days after (5 days pre and post for long-acting NSAIDs) administration of pemetrexed disodium
- •No concurrent anticonvulsants that are metabolized by the cytochrome P450 pathway
排除标准
- 未提供
结局指标
主要结局
Number of Patients With Grade ≥ 3 Toxicity (Phase I)
时间窗: First cycle of treatment (3 weeks)
Grade 3/4 toxicity occurring in a patient within 1 cycle.
Number of Patients Experiencing a Dose-limiting Toxicity (Phase I)
时间窗: Up to 36 months
Grade 4 thrombocytopenia or grade 3 thrombocytopenia associated with bleeding, requirement for transfusion or lasting \>7 days; febrile neutropenia; grade 3 neutropenia associated with infection; any other grade \>/=3 non-hematologic toxicity considered by the investigator to be related to study drug.
Number of Participants Who Experience Adverse Events (Phase I)
时间窗: Throughout the entire study (up to 36 months).
Number of participants with treatment-related adverse events as assessed by CTCAE v3.0 (Phase I).
Number of Patients Who Responded to Study Treatment (Phase II)
时间窗: From start of treatment until disease progression/recurrence.
To determine the response rate of bortezomib in combination with pemetrexed in patients with advanced NSCLC. Response rate was assessed by CT scan. CT scans was performed at baseline and every two cycles (prior to 3rd and 5th cycle). The evaluation of response was based on standard RECIST criteria.
次要结局
- Maximum Tolerated Dose of Bortezomib in Combination With Pemetrexel (Phase I)(Up to 36 months)
- Number of Participants With Response to Therapy as Measured by RECIST (Phase I)(Up to 36 months)
- Analysis of Molecular Determinants in Tumor Samples (Phase II)(Up to 36 months)
- Effect of Bortezomib on Over Expression of NF-kB, BCL-2, and BCL-xL (Phase II)(Up to 36 months)
- Importance of Folate-associated Gene Expression and Response or Outcome (Phase II)(Up to 36 months)
- Number of Participants With Toxicities (Phase II)(Up to 36 months)
- Number of Patients With Toxicity by NCI CTC v3.0 (Phase I)(Up to 36 months)