Phase I Dose Escalation Study of Carboplatin, Pemetrexed and Exemestane in Post-menopausal Women With Metastatic Non-squamous NSCLC
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 8
- 试验地点
- 1
- 主要终点
- Tabulation, grading, and attribution of serious adverse events (SAEs) and adverse events (AEs) using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0
研究概览
简要总结
This phase I trial studies the side effects and best dose of exemestane in combination with pemetrexed disodium and carboplatin in treating post-menopausal women with stage IV non-small cell lung cancer. Exemestane may stop the growth of tumor calls by blocking some of the enzymes need for cell growth. Drugs used in chemotherapy, such as pemetrexed disodium and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving exemestane together with pemetrexed disodium and carboplatin may kill more tumor cells
详细描述
PRIMARY OBJECTIVES:
I. Evaluate the safety and tolerability of escalating doses of exemestane when given with pemetrexed (pemetrexed disodium) and carboplatin in post-menopausal women with stage IV non-squamous, non-small cell lung cancer (NSCLC).
SECONDARY OBJECTIVES:
I. Determine the objective tumor response rate (defined by Response Evaluation Criteria in Solid Tumors [RECIST] 1.1) in patients treated with pemetrexed, carboplatin and exemestane.
II. Evaluate the pharmacokinetic profile of pemetrexed, carboplatin and exemestane.
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
- Female
- 接受健康志愿者
- 否
入选标准
- •Ability to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use protected health information (PHI)
- •Histologically or cytologically confirmed, treatment-naive (or status post a single treatment regimen of a tyrosine kinase inhibitor as a single agent) stage IV non-squamous, NSCLC
- •Measurable disease according to modified RECIST version 1.1
- •Eastern Cooperative Oncology Group (ECOG) performance status =< 1
- •Expected survival time of >= 3 months in the opinion of the investigator
- •Postmenopausal women; women are eligible if they are postmenopausal (older than 50 years of age with no spontaneous menses for at least 12 months; or 50 years of age or younger either with no spontaneous menses [amenorrheic] within 12 months of randomization [e.g., spontaneous or secondary to hysterectomy] and a follicle-stimulating hormone level within the postmenopausal range or with prior bilateral oophorectomy)
- •Ability to provide a formalin-fixed, paraffin-embedded (FFPE) tumor tissue sample containing representative tumor tissue from a previously obtained biopsy/resection that meets specific tissue sample requirements at screening
排除标准
- •History of another primary cancer within 3 years prior to day 1 with the exception of curatively treated skin cancer (other than melanoma) or curatively treated cervical carcinoma in-situ
- •Untreated central nervous system (CNS) involvement; (treated CNS involvement is permitted only if the patient is not currently on steroid therapy or has remained on a stable, unchanged dose of steroid for >= 3 weeks)
- •Recent major surgery within the prior 4 weeks; (mediastinoscopy or placement of a central venous access will be allowed as long as placement was more than 7 days prior to receiving study drug)
- •Any prior or concurrent investigational or standard therapy for treatment of metastatic NSCLC including radiation therapy, chemotherapy, biological therapy (with the exception of a single treatment regimen of a tyrosine kinase inhibitor as a single agent, which must be completed 28 days prior to day 1), hormonal therapy, or immunotherapy; (palliative-targeted radiotherapy for brain or bone metastases is permitted providing it has been at least 14 days prior to day 1)
- •History of hormone replacement therapy (estrogens with or without progestin) or an aromatase inhibitor (anastrazole, letrozole, exemestane) within 8 weeks prior to day 1
- •Osteoporosis complicated by pathologic fracture
- •Concurrent investigational agents for non-malignant disease or prior investigational agents for non-malignant disease within 4 weeks or 5 half-lives (whichever is shorter) prior to day 1
- •Concurrent cytotoxic or immunosuppressive therapy for non-malignant disease (e.g., for rheumatoid arthritis or lupus)
- •Absolute neutrophil count (ANC) < 1500/mL
- •Platelet count < 100,000/mL
- •Hemoglobin < 9.0 g/dL
- •Serum bilirubin > 1.5 x upper limits of normal (ULN)
- •Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) > 2.5 x ULN (AST and ALT > 5 x ULN for subjects with liver metastasis)
- •Glomerular filtration rate (GFR) =< 50
- •Albumin =< 2.5 g/dL
- •Known history of or positive test result for human immunodeficiency virus (HIV)
- •Active infection (including HIV/acquired immune deficiency syndrome [AIDS], hepatitis B, or hepatitis C infection) requiring systemic antibiotics, antivirals, or antifungals
- •History of myocardial infarction within 12 months prior to day 1 or clinically significant coronary disease
- •New York Heart Association grade II or greater congestive heart failure
- •Unstable coronary disease or clinically significant electrocardiogram (ECG) (12-lead) abnormalities, as determined by the investigator
- •Inability to comply with study and follow-up procedures
- •Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that leads to reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the subject at high risk from treatment complications
- •Other unspecified reasons that, in the opinion of the investigator or sponsor, make the subject unsuitable for enrollment
研究组 & 干预措施
Treatment (exemestane, pemetrexed disodium, and carboplatin)
Patients receive exemestane PO QD on days 1-28 and pemetrexed disodium IV over 15 minutes and carboplatin IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.
干预措施: exemestane (Drug)
Treatment (exemestane, pemetrexed disodium, and carboplatin)
Patients receive exemestane PO QD on days 1-28 and pemetrexed disodium IV over 15 minutes and carboplatin IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.
干预措施: pemetrexed disodium (Drug)
Treatment (exemestane, pemetrexed disodium, and carboplatin)
Patients receive exemestane PO QD on days 1-28 and pemetrexed disodium IV over 15 minutes and carboplatin IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.
干预措施: carboplatin (Drug)
Treatment (exemestane, pemetrexed disodium, and carboplatin)
Patients receive exemestane PO QD on days 1-28 and pemetrexed disodium IV over 15 minutes and carboplatin IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.
干预措施: laboratory biomarker analysis (Other)
Treatment (exemestane, pemetrexed disodium, and carboplatin)
Patients receive exemestane PO QD on days 1-28 and pemetrexed disodium IV over 15 minutes and carboplatin IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.
干预措施: pharmacological study (Other)
Treatment (exemestane, pemetrexed disodium, and carboplatin)
Patients receive exemestane PO QD on days 1-28 and pemetrexed disodium IV over 15 minutes and carboplatin IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.
干预措施: questionnaire administration (Other)
Treatment (exemestane, pemetrexed disodium, and carboplatin)
Patients receive exemestane PO QD on days 1-28 and pemetrexed disodium IV over 15 minutes and carboplatin IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.
干预措施: quality-of-life assessment (Procedure)
结局指标
主要结局
Tabulation, grading, and attribution of serious adverse events (SAEs) and adverse events (AEs) using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0
时间窗: Up to 3 years
次要结局
- Quality of life in patients treated with pemetrexed disodium, carboplatin and exemestane(Up to 3 years)
- Proportion achieving clinical response(Up to 3 years)