NCT00171834已完成1 期
An Open Label, Phase I/II Dose Escalating Study Evaluating the Safety and Efficacy of EPO906, qw3, in Patients With Non-small Cell Lung Cancer.
适应症
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 89
- 试验地点
- 8
- 主要终点
- Phase I: Number of Total Dose-limiting Toxicity (DLT) During Dose Escalation to Determine Maximum Tolerated Dose (MTD)
研究概览
简要总结
The study objective is to evaluate the maximum tolerated dose, safety and efficacy of patupilone in patients with NSCLC who have progressed after prior chemotherapy.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 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
- •Patients with histologic or cytologic confirmation of unresectable locally advanced or metastatic NSCLC (stage IIIB with pleural effusion only / stage IV) documented before first line therapy.
- •Prior treatment with a platinum-containing regimen
- •Age ≥18 years.
- •Performance status of 0-1 on the WHO scale.
- •Life expectancy of ≥3 months.
- •NSCLC patients should have at least one measurable lesion as defined by modified RECIST criteria. If the patient has had previous radiation to the marker lesion(s), the lesion must have demonstrated progression since the radiation.
- •NSCLC patients with controlled brain metastases are eligible to be enrolled in the brain metastases cohort at the MTD. "Controlled brain metastases" patients are defined as patients who are neurologically stable, i.e. have not experienced an increase in dose of steroidal or anticonvulsive therapy for at least 14 days prior to study entry.
- •Patients with brain metastases must be verified to have metastases secondary to NSCLC based on histology of primary and by temporal sequence of events (note: these patients are eligible even if lung disease is quiescent).
- •Patients with brain metastases must show evidence of residual disease or progression of disease since prior radiological or surgical therapy.
- •Patients with brain metastases should have at least one bidimensionally measurable intracranial lesion of minimum diameter 2 cm. Multifocal disease is permitted, but the eligibility of BM patients presenting with more than 6 intracranial lesions should be discussed with Novartis prior to enrolling the patient.
- •Patients with adequate hematologic parameters:
- •ANC ≥1.5 x 10^9/L;
- •Hb ≥9.0 g/dL,
- •Platelet count ≥100 x 10^9/L (untransfused).
- •Demonstrate the following blood chemistry laboratory values:
- •total bilirubin ≤ 1.5 x ULN;
- •AST/ALT ≤ 2.5 X ULN; (≤ 5 x ULN if hepatic metastasis is present)
- •alkaline phosphatase ≤ 2.5 x ULN; (≤ 5 x ULN if hepatic and/or bone metastasis are present)
- •serum creatinine < 2 x ULN.
- •Female patients must have a negative serum pregnancy test at screening. (Not applicable to patients with bilateral oophorectomy and/or hysterectomy or to those patients who are postmenopausal).
- •All patients of reproductive potential must agree to use an effective method of contraception during the study and three months following termination of treatment.
- •All patients must use a barrier method for contraception for sexual intercourse or avoid this for the first 5 days after patupilone infusion.
- •Written informed consent must be obtained.
排除标准
- •Patients who have received more than one prior chemotherapy regimen or any other systemic antineoplastic treatment including immunotherapy.
- •Patients who have received any investigational compound within the past 28 days or who are planning to receive other investigational drugs while participating in the study.
- •Patients with brain metastases who have received any prior chemotherapy regimen or any other systemic antineoplastic treatment for brain metastases.
- •Patients with brain metastases who have experienced a dose increase of 25% or more above previous dose, in concomitant steroidal or anticonvulsive therapy within 14 days prior to study entry.
- •Patients with brain metastases receiving steroidal or anticonvulsive therapy for whom a dose increase has been required within 14 days prior to start of study drug.
- •Patients with brain metastases who have leptomeningeal disease.
- •Patients with brain metastases who have extracranial metastases in more than two organs.
- •Patients with any peripheral polyneuropathy > Grade
- •Patients with unresolved diarrhea > Grade
- •Patients receiving hematopoietic growth factors except erythropoietin (refer Section 3.4.4).
- •Severe cardiac insufficiency (NYHA III or IV), with uncontrolled and/or unstable cardiac or coronary artery disease.
- •Patients taking warfarin or other agents containing warfarin, with the exception of low dose warfarin (1 mg or less daily) administered prophylactically for maintenance of in-dwelling lines or ports.
- •Patients who have not recovered fully from surgery for any cause, including brain metastases patients who have had a biopsy or surgical resection of the brain tumor within 2 weeks prior to starting study drug or who are not fully recovered from any prior biopsy or surgical resection.
- •Patients who have received radiation therapy or chemotherapy within the last four weeks. Palliative radiotherapy of metastasis in extremities is allowed but such lesions cannot be used as tumor markers.
- •Patients with the presence of active or suspected acute or chronic uncontrolled infection, including abscess or fistulae.
- •Patients known to be HIV positive.
- •History of another malignancy within 3 years prior to study entry, except curatively treated non-melanotic skin cancer or cervical cancer in situ.
- •For patients enrolling in the brain metastases cohort, any of the following exclusions to MRI imaging:
- •Cardiac pacemaker Ferromagnetic metal implants other than those approved as safe for use in MRI scanners Claustrophobia Obesity (exceeding the limits of scanning equipment)
- •Pregnant or lactating females.
- •A history of noncompliance to medical regimens or inability or unwillingness to return for all scheduled visits.
- •Other protocol-dependent inclusion / exclusion criteria may apply
结局指标
主要结局
Phase I: Number of Total Dose-limiting Toxicity (DLT) During Dose Escalation to Determine Maximum Tolerated Dose (MTD)
时间窗: Cycle 1 (21 days)
The MTD was defined as the highest dose of patupilone administered every three weeks (q3w) where not more than one out of six patients experienced a DLT using a standard 3+3 design. Dose escalation started at 6.5 mg/m\^2 until MTD in steps of 0.5 mg/m\^2 until 12 mg/m\^2, then in steps of 1 mg/m\^2 till 13.0 mg/m\^2. DLTs were assessed during cycle 1. During this time frame, no more than one DLT occurred in any of the explored dose levels up to 13 mg/m\^2, thus, the MTD as defined by the protocol was not reached in this study.
Phase II: Number of Participants With Best Overall Response Rate (ORR) According to Response Evaluation Criteria in Solid Tumors (RECIST)
时间窗: At baseline, then every second cycle (approximately every 6 weeks), until disease progression or discontinuation. Average 18 weeks.
Overall response is the number of participants who had a complete response (CR) or a partial response (PR) based on local investigator's assessment of RECIST criteria. Per RECIST: CR, all detectable tumor has disappeared; PR, a \>=30% decrease in the sum of the longest dimensions of the target lesions (TLs) taking as a reference the baseline sum, no worsening of non-TLs, and no new lesions; Progressive disease (PD), a \>=20% increase in TLs, clearly worsening of non-TLs, or emergence of new lesions; Stable Disease (SD), small changes that do not meet previously given criteria.
次要结局
- Number of Participants With Best Overall Response-Phase I(Best achieved overall response according to RECIST from start of study until study discontinuation. Imaging was assessed every second cycle (ie. approximately every 6 weeks) until disease progression or discontinuation. Average 18 weeks)
- Overall Survival Time-Phase I and Phase II(From start of study drug to date of death due to any cause. Follow-up after treatment discontinuation approximately every 3 months until approximately 70% of participants have reached the survival endpoint. Average 9.75 months)
- Time to Progression (TTP)-Phase I and Phase II(From baseline, then every second cycle (i.e. approximately every 6 weeks), until disease progression or discontinuation from study. Average 18 weeks)
- Duration of Stable Disease-Phase I and Phase II(Imaging was assessed every second cycle (i.e. approximately every 6 weeks), until disease progression or discontinuation from treatment . Average 18 weeks)
- Time to Overall Response -Phase I and Phase II(From baseline, then every second cycle (i.e. approximately every 6 weeks), until disease progression or discontinuation from study. Average 18 weeks)
- Duration of Overall Response -Phase I and Phase II(Duration of response according to RECIST from start of study until study discontinuation. Duration of response was assessed every second cycle ( i.e. approximately every 6 weeks) until disease progression or discontinuation from study. Average 18 weeks)
研究者
研究点 (8)
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