ICIs Neoadjuvant Therapy in Resectable Non-Small-Cell Lung Cancer
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 27
- 试验地点
- 1
- 主要终点
- Safety and Adverse effects
研究概览
简要总结
The proposed study will evaluate the safety and feasibility of preoperative administration nivolumab in patients with high-risk resectable NSCLC, and will facilitate a comprehensive exploratory characterization of the tumor immune milieu and circulating immune cells and soluble factors in these patients. Data obtained in this study will provide valuable information for planning further prospective clinical trials of anti-PD-1 or anti-PD-L1 in NSCLC, both in the peri-operative and advanced disease setting.
详细描述
The proposed study will evaluate the safety and feasibility of preoperative administration nivolumab in patients with high-risk resectable NSCLC, and will facilitate a comprehensive exploratory characterization of the tumor immune milieu and circulating immune cells and soluble factors in these patients. Data obtained in this study will provide valuable information for planning further prospective clinical trials of anti-PD-1 or anti-PD-L1 in NSCLC, both in the peri-operative and advanced disease setting. Ultimately, it is highly desirable to discover prospective biomarkers of response and toxicity to allow patients with NSCLC who are most likely to derive benefit to receive anti-PD-1 or anti-PD-L1 treatment, and conversely to minimize the risk of toxicity and ineffective treatment for patients who are unlikely to benefit.
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 proven non-small-cell lung cancer (core biopsy required).
- •Squamous or non-squamous histology.
- •Diagnostic core biopsy specimens must be reviewed by a faculty pathologist at The Second Affiliated Hospital Zhejiang University School of Medicine.
- •Either a formalin fixed paraffin block or a minimum of fifteen 5-micron tissue sections (slides) of tumor biopsy sample must be available for biomarker evaluation (study pathologist must review for adequacy of sampling). This can be obtained from archived tissues, or from a new biopsy if needed.
- •Stage - High risk NSCLC with resection option for potential cure, as assessed by a faculty surgeon at The Second Affiliated Hospital Zhejiang University School of Medicine. This may include clinical stage IA3 (≥2cm), II and IIIA(see Appendix A). Subjects with N3 nodal involvement are not included.
- •ECOG performance status 0-
- •Adequate organ function as follows:
- •Leukocytes ≥ 2,000/mm
- •Absolute neutrophil count (ANC) ≥ 1000/mm
- •Platelet count ≥ 100,000/mm
- •Hemoglobin ≥ 9 g/dL.
- •Creatinine ≤ 1.5 x ULN or creatinine clearance (CrCl) ≥40 mL/min (if using the Cockcroft-Gault formula below):
- •Female CrCl = (140 - age in years) x weight in kg x 0.85 72 x serum creatinine in mg/dL.
- •Male CrCl = (140 - age in years) x weight in kg x 1.00 72 x serum creatinine in mg/dL.
- •Total Bilirubin ≤ 1.5 x ULN (except subjects with Gilbert Syndrome, who can have total bilirubin < 3.0 mg/dL).
- •AST(SGOT), ALT(SGPT), and alkaline phosphatase ≤ 3 times the upper limit of normal.
- •Subjects must have adequate lung function to permit surgical resection determined by pre-enrollment pulmonary function tests to include DLCO.
- •The effects of nivolumab on the developing human fetus are unknown. For this reason, women of child-bearing potential (WOCBP) and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation and for up to 23 weeks after the last dose of nivolumab. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Sexually active fertile men must use effective barrier birth control if their partners are WOCBP for up to 31 weeks after the last dose of nivolumab. WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within two weeks of registration. Women must not be breastfeeding.
- •Patient understands the study regimen, its requirements, risks and discomforts and is able and willing to sign the informed consent form. Voluntary signed and dated IRB/IEC approved written informed consent form in accordance with regulatory and institutional guidelines must be obtained before the performance of any protocol related procedures that are not part of normal patient care. Subjects must be competent to report AEs, understand the drug dosing schedule and use of medications to control AEs.
排除标准
- •Subjects are excluded if they have an active, known or suspected autoimmune disease. Subjects are permitted to enroll if they have vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger.
- •Subjects are excluded if they have a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease. As there is potential for hepatic toxicity with nivolumab or nivolumab/ipilimumab combinations, drugs with a predisposition to hepatoxicity should be used with caution in patients treated with nivolumab-containing regimen.
- •Administration of chemotherapy or any other cancer therapy in the pre-operative period.
- •Subjects with active concurrent malignancies are excluded i.e. cancers other than NSCLC (except non melanoma skin cancers, in situ bladder, gastric, breast, colon or cervical cancers/dysplasia).
- •Subjects with brain metastasis are excluded from this study, and all patients should have brain imaging (either MRI brain or CT brain with contrast) prior to enrollment.
- •Subjects with a history of symptomatic interstitial lung disease.
- •Active systemic infection requiring therapy, positive tests for Hepatitis B surface antigen or Hepatitis C ribonucleic acid (RNA).
- •Known positive history or positive test for Human Immunodeficiency Virus or
- •Acquired ImmunoDeficiency Syndrome (AIDS).
- •History of allergy to study drug components.
- •Women who are pregnant or nursing.
- •Men with female partners (WOCBP) that are not willing to use contraception.
- •Prior therapy with an anti-PD-1, anti-PD-L1, anti-PDL-2, or anti-CTLA-4 antibody (or any other antibody targeting T cell co-regulatory pathways).
- •Underlying medical conditions that, in the Investigator's opinion, will make the administration of study drug hazardous or obscure the interpretation of toxicity or adverse events.
- •Prisoners or subjects who are involuntarily incarcerated or compulsorily detained for treatment of either a psychiatric or physical (e.g. infectious disease) illness.
研究组 & 干预措施
Single arm
干预措施: Nivolumab, Pembrolizumab, Toripalimab, Sintilimab, Sintilimab, Tislelizumab, Durvalumab (Drug)
结局指标
主要结局
Safety and Adverse effects
时间窗: 8 weeks
Safety will be measured by drawing safety labs. (CBC and a Chemistry Panel will be drawn at 2 week intervals during Nivolumab administration). Grade 3 and 4 lab abnormalities will be recorded from both participating sites. Safety will also be measured by recording Grade 3 and 4 CTCAE 4.03 listed adverse events that occur while a subject is participating in the study.
次要结局
- Radiographic Response(5 weeks)
- Pathologic Response(6 weeks)
- Rate of Enrollment(8 weeks)