A Phase II Open-Label Trial of AUY922, an HSP90 Inhibitor, in Patients With ALK-Rearranged Advanced Non-Small Cell Lung Cancer and Acquired Resistance to Prior ALK Tyrosine Kinase Inhibition
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 6
- 试验地点
- 4
- 主要终点
- Objective 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 and that research doctors are trying to find out more about it-such as the safest dose to use, the side effects it may cause and if the drug is effective for treating your type of cancer. 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 ALK gene. This mutated gene helps cancer cells grow. There is a drug (crizotinib) that has been approved by the FDA for the treatment of people with NSCLC who have mutations in the ALK gene. Most people respond to crizotinib initially. Over time, however, patients may stop responding (become resistant) to crizotinib because of additional changes in the ALK gene that makes crizotinib ineffective.
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 that have become resistant to drugs like crizotinib. Only participants with changes in the ALK gene will be allowed to participate in this study.
The purpose of this study is to test the safety of AUY922 and determine how well AUY922 treats participants with advanced, ALK-positive NSCLC.
详细描述
If you agree to participate in this research study, you will be asked to undergo some screening tests or procedures to find out if you can be in the research study. 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 you do not take part in the research study. If you have had some of these tests or procedures recently, they may or may not have to be repeated. These test include a medical history, physical exam, performance status, assessment of tumor, EKG, echocardiogram or multigated acquisition scan, eye exam, blood draw, blood pregnancy test, urine tset and collection of a piece of stored tumor tissue. If these tests show you are eligible to participate in the research study, you will begin the study treatment. If you do not meet the eligibility criteria, you will not be able to participate in this research study.
Study treatment is given in 21 day cycles. AUY922 is given by IV (into a vein). This is called an infusion. You will receive an infusion of AUY922 jon 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. At every visit, you should tell the study staff how you are feeling and whether your health has changed. you may have other lab tests done as part of the the care of your cancer in addition to those listed below.
Cycle 1, Day 1: physical examination, performance status, EKG, Blood draw and routine urine tests.
Cycle 1, Day 2: EKG
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 advanced NSCLC
- •Tumor characterized by abnormalities in ALK
- •Required to provide archival tissue in the form of 5 formalin fixed paraffin embedded sections
- •Have acquired resistance to treatment with an ALK-TKI
- •At least one measurable lesion as defined by RECIST criteria
- •Life expectancy of at least 12 weeks
排除标准
- •Pregnant or breastfeeding
- •Discontinued ALK TKI more than four weeks prior to enrollment
- •Unresolved diarrhea greater than or equal to CTCAE grade 1
- •Not willing to use double barrier methods of contraception
- •Prior anti-neoplastic treatment with any HSP90 or HDAC inhibitor compound
- •Have received cytoxic chemotherapy in the intervening period since discontinuation of an ALK-TKI
- •Have undergone major surgery within 2 weeks prior to starting study drug
- •Any concurrent or uncontrolled illness
- •Any known disorders due to a deficiency in bilirubin glucuronidation
- •Taking therapeutic doses of warfarin
- •Any serious cardiac disorders or abnormalities
- •Concurrent malignancies or invasive cancers diagnosed within the past 2 years except for adequately treated basal cell cancer of the skin or in situ cancers
- •Known to be HIV positive
- •Known hypersensitivity to any of the study drugs or their excipients
- •Participation in another clinical study within 30 days before the first study treatment
研究组 & 干预措施
AUY922
Via intravenous infusion on Days 1, 8 and 15 of each 21 day cycle (once per week). Infusion lasts approximately 60 minutes
干预措施: AUY922 (Drug)
结局指标
主要结局
Objective Response Rate
时间窗: Baseline and then every six weeks (± 7 days), until the time of disease progression
The number of participants that achieved either a complete response (CR) or a partial response (PR) as assessed by Response Evaluation Criteria in Solid Tumors (RECIST v1.1). * 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
- Disease Control Rate(Baseline and then every six weeks (± 7 days), until the time of disease progression)
- ALK Translocation Variant Type(Baseline)
- Progression-free Survival(From the start of treatment until the time of death or progression)
- Number of Participants With Concurrent KRAS Mutations(Baseline)
- ALK Mutation Status(Baseline, end of treatment)
- Number of Participants Who Develop Adverse Events on AUY922(From the start of treatment until 30 days after last dose was received)
- Median Overall Survival(From the start of treatment until death or withdrawal from the study)
研究者
Alice Shaw
Principal Investigator
Massachusetts General Hospital