Health Condition 1: C343- Malignant neoplasm of lower lobe,bronchus or lung Health Condition 2: C340- Malignant neoplasm of main bronchus Health Condition 3: C342- Malignant neoplasm of middle lobe,bronchus or lung Health Condition 4: C348- Malignant neoplasm of overlappingsites of bronchus and lung Health Condition 5: C349- Malignant neoplasm of unspecifiedpart of bronchus or lung Health Condition 6: C341- Malignant neoplasm of upper lobe,bronchus or lung
Conditions
Interventions
Intervention1: 3 cycles of neoadjuvant chemotherapy(Taxane/Pemetrexed and Platinum) with low dose Immunotherapy (Nivolumab40mg): Eligible patients will receive 3 cycles of neoadjuvant chemotherapy(Tax
Sponsors
Tata Memorial Centre
Eligibility
Inclusion criteria
Inclusion criteria: 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
Exclusion criteria
Exclusion criteria: 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Pathological complete response rates (pCR)Timepoint: After surgery . with 3-4 months of enrollment | — |
Secondary
| Measure | Time frame |
|---|---|
| 2year Event Free Survival (EFS) Overall Survival (OS) Patterns of treatment failure Quality of life (QOL) assessment Toxicity assessment Treatment completion rates Overall response rate (ORR) as per RECIST v1.1 Major pathological response rates (MPR) R0 resection rates Post-operative complication rates using Klavien-Dindo classification Surgical conversion rates Timepoint: 2-year Event-Free Survival EFS: Time from randomization to disease recurrence, progression, or death from any cause. Overall Survival OS: Time from randomization to death from any cause. Patterns of Treatment Failure: Classified as locoregional or distant recurrences, assessed at follow-up intervals. Quality of Life (QOL) Assessment: Evaluated using EORTC QLQ-C30 and QLQ-OE at baseline, after neoadjuvant therapy, first post-surgery OPD visit, 90 days post-surgery, and 180 days post-surgery. Toxicity Assessment: Adverse events recorded from randomization until 90 days post-surgery or 30 days post-adjuvant therapy completion. Treatment Completion Rates: Determined by the number of patients completing neoadjuvant therapy, surgery, and adjuvant therapy if indicated. Overall Response Rate (ORR) as per RECIST v1.1: Calculated after neoadjuvant therapy. Major Pathological Response Rates (MPR): Assessed post-surgery with less than and equal to 10 percent residual tumor. R0 Resection Rates: Determined post-surgery based on negative microscopic margins. Post-operative Complication Rates: Evaluated at 30 and 90 days post-surgery using Clavien-Dindo classification. Surgical Conversion Rates: Assessed intraoperatively for conversion from minimally invasive to open surgery ;Biomarker analysisTimepoint: 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 | — |
Countries
India
Contacts
Public ContactDr Minit Shah
Tata Memorial Centre
Outcome results
None listed