A Phase 2 Trial of Bortezomib in KRAS-Mutant Non-Small Cell Lung Cancer in Never Smokers or Those With KRAS G12D
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 17
- 试验地点
- 5
- 主要终点
- Radiographic Response Rate
研究概览
简要总结
The purpose of this study is to test the drug Bortezomib to see how well it works. The investigators want to find out what effects, good or bad, it has on patients with a limited smoking history or who have a specific mutation associated with their lung cancer.
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
- •Pathologic or cytologic evidence of non-small cell lung cancer (NSCLC)
- •Documented KRAS mutation
- •History of smoking < 100 cigarettes (never-smoker) OR patient with a KRAS G12D mutation regardless of smoking history
- •Clinical stage IIIB/IV or recurrent/medically inoperable NSCLC
- •Age ≥ 18 years
- •Three (3) weeks since last chemotherapy, and three (3) weeks since prior radiation therapy and recovered from treatment
- •Karnofsky performance status ≥ 70%
- •Adequate hematologic, and/or hepatic function WBC ≥ 3,000/ul or absolute neutrophil count ≥ 1,000/ul Hemoglobin ≥ 9.0 g/dl Platelet count ≥ 100,000/ul AST ≤ 2.0 X ULN (upper limit of normal)
- •Total bilirubin ≤1.5 x ULN Measurable indicator lesions by RECIST v1.1 criteria.
- •Voluntary written informed consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care.
- •Female subject is either postmenopausal for at least 1 year before the screening visit, is surgically sterilized or if they are of childbearing potential, agree to practice 2 effective methods of contraception from the time of signing the informed consent form through 30 days after the last dose of bortezomib, or agree to completely abstain from heterosexual intercourse.
- •Male subjects must agree to 1 of the following: practice effective barrier contraception during the entire study treatment period and through a minimum of 30 days after the last dose of study drug, or completely abstain from heterosexual intercourse.
排除标准
- •Uncontrolled central nervous system metastases defined as any lesion which is either a. symptomatic, or requiring escalating doses of corticosteroids
- •Significant medical history or unstable medical condition such as uncontrolled diabetes myocardial infarction within 6 months prior to enrollment New York Heart Association Class III or IV heart failure severe uncontrolled ventricular arrythmias uncontrolled angina ECG evidence of acute ischemia or active conduction system abnormalities
- •Baseline ≥ grade 2 peripheral neuropathy by CTCAE v 4.0 (Appendix B)
- •Known hypersensitivity to boron or mannitol
- •Female patients who are pregnant/lactating or have a positive serum or urine β-hCG pregnancy test
- •Serious medical or psychiatric illness likely to interfere with participation in this clinical study.
- •No active concurrent malignancy, with the exception of in-situ malignancy completely resected basal cell carcinoma or squamous cell carcinomas of the skin low-risk prostate cancer after curative therapy
- •Participation in clinical trials with other investigational agents not included in this trial, within 14 days of the start of this trial and throughout the duration of this trial
研究组 & 干预措施
Bortezomib
Bortezomib will be administered by subcutaneous injection twice weekly for 2 weeks (Days 1, 4, 8, and 11) at 1.3 mg/m2/dose followed by a 10-day rest period for a 21 day cycle. Dose modifications are permitted as per a prescribed algorithm. Acyclovir at 400mg daily is recommended as prophylaxis for herpes zoster. Restaging scans, with evaluation of response, will be done every 2 cycles (6 weeks of treatment ± 7 days). Treatment will continue until clinical disease progression, unacceptable toxicity, treatment delay > 2 weeks, or at the discretion of the treating physician or patient.
干预措施: Bortezomib (Drug)
Bortezomib
Bortezomib will be administered by subcutaneous injection twice weekly for 2 weeks (Days 1, 4, 8, and 11) at 1.3 mg/m2/dose followed by a 10-day rest period for a 21 day cycle. Dose modifications are permitted as per a prescribed algorithm. Acyclovir at 400mg daily is recommended as prophylaxis for herpes zoster. Restaging scans, with evaluation of response, will be done every 2 cycles (6 weeks of treatment ± 7 days). Treatment will continue until clinical disease progression, unacceptable toxicity, treatment delay > 2 weeks, or at the discretion of the treating physician or patient.
干预措施: Acyclovir (Drug)
结局指标
主要结局
Radiographic Response Rate
时间窗: 2 years
The following evaluations will be conducted to assess the efficacy of bortezomib - radiographic response rate by RECIST v1.1. 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
次要结局
- Progression Free Survival(2 years)
- Overall Survival(2 years)
- Participants Evaluated for Toxicity(2 years)