The Maximum Tolerated Dose and to Evaluate Safety and Efficacy of Belinostat (PXD-101) in Combination With Paclitaxel Plus Carboplatin in Chemotherapy-Naive Patients With Stage IV Non-Small-Cell Lung Cancer (NSCLC)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 23
- 试验地点
- 4
- 主要终点
- To determine the Maximum Tolerated Dose ( MTD) of belinostat in combination with carboplatin and paclitaxel in patient with Stage IV non-small cell lung cancer who has received no prior systemic chemotherapy.
研究概览
简要总结
To define Phase 1/2 Maximum Tolerated Dose Study of Belinostat (PXD-101) in Combination with Paclitaxel plus Carboplatin in Chemotherapy-Naive Patients with Stage IV Non-Small-Cell Lung Cancer (NSCLC).
详细描述
This is a Phase 1/2, multi-center, open label single arm study. Patients meeting all inclusion and exclusion criteria will receive up to 6 cycles of combination therapy of belinostat plus carboplatin (AUC 6) and paclitaxel 200 mg/m2.
During phase I the Maximum Tolerated Dose (MTD) of belinostat in combination with carboplatin and paclitaxel will be determined in patients with Stage IV non-small cell lung cancer who have received no prior systemic chemotherapy. The dose escalation study will be conducted using traditional escalation rule of 3+3 design, during the first cycle of therapy. Belinostat will be assessed at a starting dose level of 1000 mg/m2 and multiple dose levels may be evaluated. Doses of belinostat, carboplatin and paclitaxel will remain constant throughout the study, unless dose modification is required by toxicity. Treatment is given on days 1-5 of every 21-day cycle. Routine safety evaluations will be conducted on days, 1, 8, and 15 of every cycle. Tumor measurement will be done after every 2 cycles of the treatment.
Additional 20 patients will be treated at the MTD defined dose during phase II expansion portion of the study.
All patients will receive up to 6 cycles of combination therapy and be followed until occurrence of unacceptable toxicity, disease progression, withdrawal of consent or death.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •A histologically or cytologically confirmed diagnosis of Stage IV (M1a or M1b) NSCLC. Patients with mixed non-small cell histologies are eligible
- •No prior chemotherapy for the treatment of advanced NSCLC
- •Prior adjuvant therapy for early stage lung cancer is allowed if completed ≥ 12 months prior to enrollment
- •Age >= 18 years
- •Adequate organ function
- •Any treatment with investigational agent must have completed ≥ 4 weeks prior to enrollment
- •Eastern Cooperative Oncology Group (ECOG) performance status 0-1
- •Negative pregnancy test for women of childbearing potential.
- •Patients with brain metastases allowed if:
- •Directed local therapy was completed 2 weeks prior to enrollment;
- •There is no evidence of disease progression and;
- •Steroids are not required
排除标准
- •Patients with mixed tumors of small cell features
- •Known infection with HIV, hepatitis B or hepatitis C
- •Baseline prolongation of QT/QTcF interval or required concomitant medication that may cause Torsade de Pointes
- •Preexisting ≥Grade 2 neuropathy
- •Valproic acid treatment within 2 weeks of study enrollment
- •Systemic steroids, for any indication, stabilized at >10 mg/day prednisone
- •Known allergy or hypersensitivity to any component of belinostat, paclitaxel or carboplatin
- •Co-existing active infection or any other uncontrolled medical condition likely to interfere with trial procedures
- •Active concurrent malignancy (except basal cell carcinoma or cervical intraepithelial neoplasia, other potentially cured malignancy that has been in remission for five years or prior adjuvant therapy for early stage lung cancer that is completed ≥ 12 months ago)
- •Pregnant or breast-feeding women
研究组 & 干预措施
Single arm, open label
At the study entry each patient will receive a dose level assignment which will include a specific dose level and the dose of IV belinostat in mg/m2 to be administered during the study treatment.
Belinostat will be infused over 30 minutes once daily on Days 1-5 of each 21-day cycle. On Day 3, the infusion of belinostat must be completed at least 1 hour prior to the start of the paclitaxel infusion. Dose of belinostat will be assigned at study entry. The same dose and level will remain throughout the entire study for each patient and no dose adjustment will be allowed, except due to toxicity.
干预措施: Belinostat, Carboplatin, Paclitaxel (Drug)
结局指标
主要结局
To determine the Maximum Tolerated Dose ( MTD) of belinostat in combination with carboplatin and paclitaxel in patient with Stage IV non-small cell lung cancer who has received no prior systemic chemotherapy.
时间窗: 24 Months
At study entry each eligible patient will be assigned a specific dose level and dose of IV belinostat in mg/m2, to be administered daily on Days 1 to 5 each 21 day cycle, for up to 6 cycles. Dose escalation within each patient is not allowed during this study. At each dose level cohort of up to 6 patients may be evaluated during Cycle 1 of therapy. Multiple dose levels may be evaluated to determine the Maximum Tolerated Dose (MTD) of IV belinostat, in combination with 6 cycles of IV carboplatin and paclitaxel, for chemo-naïve patients with Stage IV NSCLC.
次要结局
- Progression-free survival (PFS) when IV belinostat is administered in combination with carboplatin and paclitaxel in patients with chemotherapy naïve Stage IV M1a or M1b NSCLC(24 Months)
- Safety and Tolerability when IV belinostat is administered in combination with carboplatin and paclitaxel in patients with chemotherapy naïve Stage IV M1a or M1b NSCLC.(24 Months)
- Objective response rate (ORR) when IV belinostat is administered in combination with carboplatin and paclitaxel in patients with chemotherapy naïve Stage IV M1a or M1b NSCLC.(24 Months)
- Efficacy when IV belinostat is administered in combination with carboplatin and paclitaxel in patients with chemotherapy naïve Stage IV M1a or M1b NSCLC(24 Months)