Phase II Study of AUY922 in NSCLC Patients With Exon 20 Insertion Mutations in EGFR
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 29
- 试验地点
- 4
- 主要终点
- Overall Response Rate
研究概览
简要总结
This research study is a Phase II clinical trial, which tests the safety and effectiveness of an investigational drug to learn whether the drug works in treating a specific cancer. "Investigational" means that the drug is being studied. It also means that the FDA has not yet approved the drug for your type of cancer or for any use outside of research studies.
It has been found that some people with NSCLC have a change (mutation) in a certain gene called the EGFR gene. This mutated gene helps cancer cells grow. The majority of NSCLC patients with EGFR mutations achieve good outcomes with erlotinib or other EGFR inhibitor therapies, with a high response rate, prolonged progression-free survival and possibly improved overall survival from therapy. However, the 4% of EGFR mutant patients that harbor an exon 20 insertion mutation historically have reaped little benefit from EGFR-directed therapy due to the low affinity of this mutation for direct EGFR inhibitors, especially erlotinib and gefitinib (see Yasuda et al, Lancet Oncol 2011). This group of patients is ideal for studying other targeted therapeutic strategies that could affect the oncogene mutation in EGFR via alternative mechanisms.
AUY922 is an investigational drug that may stop cancer cells from growing abnormally. This drug has been used in other research studies. Information from those other research studies suggests that AUY922 may be effective in killing cancer cells in patients with exon 20 insertion mutations in EGFR.
The purpose of this study is to test the safety of AUY922 and determine how well AUY922 works for participants with advanced NSCLC and exon 20 insertion mutations in EGFR.
详细描述
Interested patients will be asked to undergo some screening tests and procedures to confirm that they are eligible. Many of these tests and procedures are likely to be part of regular cancer care and may be done even if it turns out that patients do not take part in the research study. If patients have had some of these tests or procedures recently, they may or may not have to be repeated. These tests and procedures include: a medical history physical exam, performance status, assessment of tumor, EKG, electrocardiogram or multigated acquisition scan, eye exam, blood draw, blood pregnancy test, urine test and collection of a piece of the stored tumor tissue.
The study treatment is given in 21 day cycles. AUY922 is given by IV (into a vein). This is called an infusion. Patients will receive an infusion of AUY922 on days 1, 8 and 15 of each cycle (once per week). The infusion will take about 60 minutes.
A schedule of clinic visits for the study is summarized below.
Cycle 1, Day 1: physical exam, including measurement of vital signs and weight; performance status; EKG; blood draw; routine urine test Cycle 1, Day 2: EKG Cycle 1, Day 3: EKG Cycle 1, Day 8: Vital signs, performance status, EKG, questions about side effects and other medications taken Cycle 1, Day 15: Physical exam, including measurement of vital signs, performance status; EKG; blood draw; questions about side effects and other medications taken Note that in Cycle 1 patients will need to stay at (or return to) the clinic for the last EKG following the Day 1 AUY922 infusion, and come to the clinic on Days 2 and 3 for EKGs.
Cycle 2 and beyond, Day 1: physical exam, including measurement of vital signs and weight; performance status; EKG; blood draw; questions about side effects and other medications taken; routine urine test Cycle 2 and beyond, Day 8: Vital signs; performance status; EKG; questions about side effects and other medications taken Cycle 2 and beyond, Day 15: Physical exam, including measurement of vital signs; performance status; EKG; blood draw; questions about side effects and other medications taken.
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
- •Histologically or cytologically confirmed stage IV or recurrent NSCLC
- •Measurable disease by RECIST 1.0
- •Must have received at least one prior line of therapy for advanced lung cancer (no maximum number)
- •Life expectancy of at least 12 weeks
排除标准
- •Pregnant or breastfeeding
- •Radiation within 2 weeks
- •Cytotoxic chemotherapy or monoclonal antibodies within 4 weeks
- •EGFR tyrosine kinase inhibitor within 2 weeks
- •Other small molecule inhibitor within 2 weeks
- •Experimental treatment within 30 days
- •Prior treatment with any HSP90 or HDAC inhibitor compound
- •Known and untreated brain metastases
- •History of allergic reactions attributed to compounds of similar chemical or biologic composition to AUY922
- •Unresolved diarrhea greater than or equal to CTCAE version 4, grade 1
- •Major surgery within 2 weeks of starting study drug or have not recovered from side effects of surgery
- •Known disorders due to a deficiency in bilirubin glucuronidation
- •Requiring use of therapeutic doses of warfarin (Coumadin)
- •History of long QT syndrome
- •History of clinically manifest ischemic heart disease, heart failure or left ventricular dysfunction
- •Clinically significant ECG abnormalities
- •Other clinically significant heart disease
- •Currently receiving treatment with any medication which has a relative risk of prolonging the QTc interval or inducing Torsades de Pointes
- •On a cardiac pacemaker
- •Concurrent malignancies or invasive cancers diagnosed within 3 years except for adequately treated basal cell cancer of the skin or in situ cancer of the cervix
- •Known to be HIV positive
研究组 & 干预措施
AUY922 Treatment Arm
AUY922 administered once weekly via intravenous, 70 mg/m2
干预措施: AUY922 (Drug)
结局指标
主要结局
Overall Response Rate
时间窗: From the start of treatment until the time of disease progression, median duration of follow-up of about 3 months
The number of participants that achieved a response to treatment as assessed by Response Evaluation Criteria is Solid Tumors (RECIST). Response is defined as having achieved either a complete response (CR) or a partial response (PR). * Complete Response (CR): Disappearance of all target lesions. Any pathological lymph node must have reduction in short axis to \< 10 mm. * Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.
次要结局
- Median Progression Free and Overall Survival(From the start of treatment until the time or death or disease progression)
- The Number of Participants With Treatment Related Serious Adverse Events(From the start of treatment until 28 days after the end of treatment)
- Exon 20 EGFR Mutations Among Participants That Responded to Treatment(Baseline, at the time of response)
研究者
Lecia V. Sequist
Principal Investigator
Massachusetts General Hospital