Neoadjuvant chemotherapy with low dose immunotherapy in resectable non-small cell lung cancer – A phase II open label single arm study
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 53
- 试验地点
- 2
- 主要终点
- Pathological complete response rates (pCR)
研究概览
简要总结
This is a phase II open label single arm study. It aims to evaluate the efficacy and safety of neoadjuvant chemotherapy with low dose nivolumab (immunotherapy) in patients with resectable non-small cell lung cancer.The objectives of the study are to evaluate post surgery response rate, overall survival, quality of life, safety, postoperative complication rates. The duration of study is 3 years. The chemotherapy will be given every 3 weeks for 3cycles. Patient will receive chemotherapy along with reduced dose of immunotherapy prior to surgery. Surgery will be done within 6-weeks of chemotherapy completion. Response scan will be done after 3 weeks of completion of neoadjuvant treatment. Adjuvant treatment will be as per standard institutional protocol. The patients willbefollowedupevery2-3months.
Aim: To evaluate the efficacy and safety of neoadjuvant chemotherapy with low-dose Nivolumab in patients with resectable non-small cell lung cancer (NSCLC).
Study Design: Phase II, single-arm, open-label, prospective study.
Sample Size: 53 patients.
Treatment Plan: Patients receive 3 cycles of neoadjuvant chemotherapy (Taxane/Pemetrexed + Platinum) with low-dose Nivolumab (40 mg IV every 3 weeks). Post-treatment response is assessed via imaging followed by surgery within 6 weeks. Adjuvant therapy is determined based on multidisciplinary discussion
Duration: 3 years (2 years accrual, 1 year follow-up).
Primary Outcome: Pathological Complete Response (pCR).
Secondary Outcomes:
- 2-year Event-Free Survival (EFS)
- Overall Survival (OS)
- Patterns of treatment failure
- Quality of Life (QOL) assessment (baseline, post-treatment, 90 and 180 days post-surgery)
- Toxicity assessment (up to 90 days post-surgery)
- Treatment completion rates
- Overall Response Rate (ORR) as per RECIST v1.1
- Major Pathological Response (MPR) rates
- R0 resection rates
- Post-operative complications (Clavien-Dindo classification)
- Surgical conversion rates
Exploratory Outcome: Biomarker analysis (baseline, post-treatment, post-surgery, follow-up).
Eligibility: Resectable Stage IIA-IIIB NSCLC, ECOG PS 0-1, adequate organ function, and negative for EGFR/ALK mutations. Exclusions include metastatic disease, active infections, autoimmune conditions, and prior immunotherapy.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 盲法
- None
入排标准
- 年龄范围
- 18.00 Year(s) 至 99.00 Year(s)（—）
- 性别
- All
入选标准
- •1 Participants with histologically confirmed Stage 2A greater than or equal to 4 cm 2B 3A 3B N2 NSCLC as per the 8th American Joint Committee on Cancer AJCC with disease that is considered resectable 2 Subjects must be treatment naive and have an Eastern Cooperative Oncology Group ECOG performance status PS 0 to 1 3 Age Male female or transgender subjects aged 18 years and above 4 Subjects must have normal organ and marrow function .Renal Estimated creatinine clearance greater than or equal to 30 mL per min 5 Pulmonary and cardiovascular functions capable of tolerating the proposed lung resection according to the surgeon 6 Patients must be adequately staged with PET CECT MRI Brain and mediastinal staging if indicated 7 Participants must have a tumor tissue and or liquid biopsy sample available for PD L1 EGFR and ALK testing In situations where PD L1 testing is not feasible and EGFR ALK mutation status is unknown inclusion of such patients will be at the principal investigator discretion 8 Measurable disease as per RECIST version 1.1 9 Patients with HIV are potentially eligible as long as they have a CD4 count greater than 200 are on concurrent HAART highly active antiretroviral therapy and have an absence of active AIDS defining conditions 10 Pregnancy Test Negative serum or urine pregnancy test at screening for women of childbearing potential 11 Contraception Highly effective contraception for both male and female subjects throughout the study and for at least 30 days after the last Nivolumab treatment administration if the risk of conception exists The effects of Nivolumab on the developing human fetus are teratogenic 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 12 Both men and women of all races and ethnic groups are eligible for this study 13 Ability to understand and the willingness to sign a written informed consent document.
排除标准
- •Patients with locally advanced unresectable or metastatic or N3 nodal disease EGFR or ALK positive mutation status Patients unfit for surgery as per treating surgeon and those affording full dose immunotherapy Subjects who are receiving any other concurrent investigational agents Immunosuppressants: Current use of immunosuppressive medication, except for the following: a.
- •Intranasal, inhaled, topical steroids, or local steroid injection such as intra-articular injection b.
- •Systemic corticosteroids at physiologic doses less than or equal to 10 mg per day of prednisone or equivalent c.
- •Steroids as premedication for hypersensitivity reactions such as CT scan premedication d.
- •Steroids for raised intracranial pressure due to the disease itself, such as steroid use for avoidance or treatment of emesis Autoimmune disease: Active autoimmune disease that might deteriorate when receiving a chemotherapeutic agent.
- •Patients with diabetes type I, vitiligo, psoriasis, or hypo- or hyperthyroid diseases not requiring immunosuppressive treatment are eligible Organ transplantation: Prior organ transplantation including allogeneic stem-cell transplantation Infections: Active infection requiring systemic therapy Hepatitis: Hepatitis B virus HBV or hepatitis C virus (HCV) infection at screening (positive HBV surface antigen with a raised HBV DNA or anti-HCV antibody screening test positive with raised HCV RNA.
- •Mere presence of HBV or HCV at screening test will not rule the patient out) Vaccination: Vaccination within 4 weeks of the first dose of Nivolumab and while on study is prohibited except for administration of inactivated vaccines Hypersensitivity to study drug: Known prior severe hypersensitivity to investigational product or any component in its formulations Cardiovascular disease: Clinically significant active cardiovascular disease including unstable angina, congestive heart failure classified as New York Heart Association Classification Class 2 or more, or serious uncontrolled cardiac arrhythmia Other severe acute or chronic medical conditions including immune colitis, inflammatory bowel disease, immune pneumonitis, chronic kidney disease, chronic liver disease, pulmonary fibrosis, or psychiatric conditions including recent within the past year or active suicidal ideation or behavior Pregnant women are excluded from this study.
- •Advise females of reproductive potential to use effective contraception during treatment and for at least one month after the last dose of Nivolumab Lactating females: There is no information regarding the presence of Nivolumab in human milk, the effects on the breastfed infant, or the effects on milk production.
- •Since many drugs are excreted in human milk, it is advised that a lactating woman should not breastfeed during treatment and for at least one month after the last dose of Nivolumab due to the potential for serious adverse reactions in breastfed infants.
结局指标
主要结局
Pathological complete response rates (pCR)
时间窗: After surgery . with 3-4 months of enrollment
次要结局
- 2year Event Free Survival (EFS)(Overall Survival (OS))
- Biomarker analysis(Biomarker Analysis: Conducted on samples collected at baseline, post-neoadjuvant therapy, post-surgery, and during follow-up every 2-3 months for the first year)
研究者
Dr Minit Shah
Tata Memorial Centre