The LIMIT KRAS Mutant NSCLC Trial: Lysosome Inhibition to Enhance MAPK Inhibition Targeting KRAS Mutant NSCLC: A Phase 2 Open Label Trial of Binimetinib and Hydroxychloroquine in Patients With Advanced KRAS Mutant Non-Small Cell Lung Cancer
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 9
- 试验地点
- 1
- 主要终点
- Objective Response Rate
研究概览
简要总结
This study will evaluate using hydroxychloroquine (HCQ) along with binimetinib as an effective method for treating cancer. All patients will receive binimetinib at a standard dose approved for other cancers. The dose of HCQ will also be fixed based on ongoing phase I studies. Eligible subjects will have lung cancer that has a mutation in a key cancer gene called KRAS, and the cancer has spread to other parts of their body.
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
- 是
入选标准
- •Metastatic or incurable NSCLC
- •Presence of a non-synonymous mutation in KRAS
- •Patient must have received at least one prior systemic therapy for metastatic NSCLC or be intolerant/ineligible/refuse available therapies with known benefit
- •Ability and willingness to sign a written informed consent document
- •Age ≥18 years old
- •At least one measureable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
- •ECOG performance status 0-1
- •Adequate organ function
- •Women of childbearing potential must have a negative serum pregnancy test performed within 72hours of the first dose of study therapy. Subjects of reproductive potential must agree to use acceptable birth control methods (see Appendix B for childbearing potential).
- •Qtc < 500 mSec on EKG
- •Must be able to swallow tablets
- •Must be willing to comply with protocol procedures (including completion of diaries and outcome measures
排除标准
- •Currently participating in or has participated in a study of an investigational agent or anticipated use of an investigational device within 4 weeks of the first dose of study treatment.
- •Untreated symptomatic central nervous system (CNS) metastases and/or carcinomatous meningitis.
- •Prior monoclonal antibody within 4 weeks prior to enrollment, or individuals who have not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
- •Known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, non-invasive bladder tumors, or in situ cervical cancer
- •Active infection requiring systemic therapy with IV antibiotics
- •History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
- •Known psychiatric or substance abuse disorders as documented in the chart that, in the opinion of the investigator, would interfere with cooperation with the requirements of the trial.
- •Pregnant or breastfeeding women
- •Anticipated receipt of any live vaccine within 30 days prior to the first dose of trial treatment.
- •Have a known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to study drug, or excipients or to dimethyl sulfoxide (DMSO).
- •Patients receiving cytochrome P450 enzyme-inducing anticonvulsant drugs (EIADs) (i.e.
- •phenytoin, carbamazepine, Phenobarbital, primidone or oxcarbazepine) within 4 weeks of the start of the study treatment
- •Known Hepatitis B Virus (HBV), or Hepatitis C Virus (HCV) infection (subjects with laboratory evidence of cleared HBV and/or HCV will be permitted)
- •Patients with a previously documented retinal vein occlusion.
- •History or evidence of increased cardiovascular risk including any of the following:
- •Current clinically significant uncontrolled arrhythmias. Exception: Subjects with controlled atrial fibrillation for > 30 days prior to randomization are eligible.
- •History of acute coronary syndromes (including myocardial infarction and unstable angina), coronary angioplasty, or stenting within 6 months prior to randomization.
- •Ejection fraction of ≤50% as measured by echocardiography or MUGA
- •Any other conditions judged by the investigator that would limit the evaluation of the subject
研究组 & 干预措施
Binimetinib and Hydroxychloroquine
Hydroxychloroquine (HCQ)in combination with Binimetinib (B). The starting dose for HCQ will be 400mg. Tablets of HCQ are available in 200 mg strength. HCQ will be administered in divided doses (every 12 hours) with or without food.
The starting dose of B is 45mg. B will be administered in divided doses (every 12 hours) with or without food
干预措施: Binimetinib Pill (Drug)
Binimetinib and Hydroxychloroquine
Hydroxychloroquine (HCQ)in combination with Binimetinib (B). The starting dose for HCQ will be 400mg. Tablets of HCQ are available in 200 mg strength. HCQ will be administered in divided doses (every 12 hours) with or without food.
The starting dose of B is 45mg. B will be administered in divided doses (every 12 hours) with or without food
干预措施: Hydroxychloroquine Pill (Drug)
结局指标
主要结局
Objective Response Rate
时间窗: 16 months
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Number of Patients With Adverse Events
时间窗: 16 months
as assessed by CTCAE v5.0
次要结局
- Progression-free Survival (PFS)(16 months)
- Overall Survival (OS)(16 months)