| CTRI Number |
CTRI/2025/02/081029 [Registered on: 20/02/2025] Trial Registered Prospectively |
| Last Modified On: |
18/08/2025 |
| Post Graduate Thesis |
No |
| Type of Trial |
Interventional |
|
Type of Study
|
Drug |
| Study Design |
Single Arm Study |
|
Public Title of Study
|
A Study to Test Chemotherapy with Low-Dose Immunotherapy Before Surgery in Treatable Lung Cancer |
|
Scientific Title of Study
|
Neoadjuvant chemotherapy with low dose immunotherapy in resectable non-small cell lung cancer – A phase II open label single arm study |
| Trial Acronym |
NIL |
|
Secondary IDs if Any
|
| Secondary ID |
Identifier |
| NIL |
NIL |
|
|
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
|
| Name |
Dr Minit Shah |
| Designation |
Associate Professor |
| Affiliation |
Tata Memorial Centre |
| Address |
Tata Memorial Hospital, Homi Bhabha Block, Department of Medical oncology,
Room no 204, 2nd floor, Dr Ernest Borges Rd, Parel East, Mumbai
Mumbai
MAHARASHTRA
400012
India |
| Phone |
7021620792 |
| Fax |
|
| Email |
minitjshah@gmail.com |
|
Details of Contact Person
Scientific Query
|
| Name |
Dr Minit Shah |
| Designation |
Associate Professor |
| Affiliation |
Tata Memorial Centre |
| Address |
Tata Memorial Hospital, Homi Bhabha Block, Department of Medical oncology,
Room no 204, 2nd floor, Dr Ernest Borges Rd, Parel East, Mumbai
Mumbai
MAHARASHTRA
400012
India |
| Phone |
7021620792 |
| Fax |
|
| Email |
minitjshah@gmail.com |
|
Details of Contact Person
Public Query
|
| Name |
Dr Minit Shah |
| Designation |
Associate Professor |
| Affiliation |
Tata Memorial Centre |
| Address |
Tata Memorial Hospital, Homi Bhabha Block, Department of Medical oncology,
Room no 204, 2nd floor, Dr Ernest Borges Rd, Parel East, Mumbai
Mumbai
MAHARASHTRA
400012
India |
| Phone |
7021620792 |
| Fax |
|
| Email |
minitjshah@gmail.com |
|
|
Source of Monetary or Material Support
|
| Tata Memorial Centre, Dr E Borges Marg Parel Mumbai 400012 |
|
|
Primary Sponsor
|
| Name |
Tata Memorial Centre |
| Address |
Tata Memorial Hospital, Homi Bhabha Block, Parel East, Mumbai- 400012 |
| Type of Sponsor |
Research institution and hospital |
|
|
Details of Secondary Sponsor
|
|
|
Countries of Recruitment
|
India |
Sites of Study
Modification(s)
|
| No of Sites = 2 |
| Name of Principal
Investigator |
Name of Site |
Site Address |
Phone/Fax/Email |
| Dr Minit Shah |
Tata Memorial Centre |
Tata Memorial Hospital, Homi Bhabha Block, Department of Medical oncology,
Room no 204, 2nd floor, Dr Ernest Borges Rd, Parel East, Mumbai
Mumbai
MAHARASHTRA |
7021620792
minitjshah@gmail.com |
| Dr BhaveshPoladia |
Thangam Hospital |
Clinical Research, A Block, Upper Basement(Room No:1506), Thangam Hospital and Thangam Cancer Center, No: 54, Dr. Sankaran Road, Namakkal - 637001, Tamilnadu, India
Namakkal
TAMIL NADU |
9819151554
bhaveshpoladia@gmail.com |
|
Details of Ethics Committee
Modification(s)
|
| No of Ethics Committees= 2 |
| Name of Committee |
Approval Status |
| Institutional Ethics Committee |
Approved |
| Institutional Ethics Committee - II |
Approved |
|
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Regulatory Clearance Status from DCGI
|
|
|
Health Condition / Problems Studied
|
| Health Type |
Condition |
| Patients |
(1) ICD-10 Condition: C343||Malignant neoplasm of lower lobe,bronchus or lung, (2) ICD-10 Condition: C340||Malignant neoplasm of main bronchus, (3) ICD-10 Condition: C342||Malignant neoplasm of middle lobe,bronchus or lung, (4) ICD-10 Condition: C348||Malignant neoplasm of overlappingsites of bronchus and lung, (5) ICD-10 Condition: C349||Malignant neoplasm of unspecifiedpart of bronchus or lung, (6) ICD-10 Condition: C341||Malignant neoplasm of upper lobe,bronchus or lung, |
|
|
Intervention / Comparator Agent
|
| Type |
Name |
Details |
| Intervention |
3 cycles of neoadjuvant chemotherapy(Taxane/Pemetrexed and Platinum) with low dose Immunotherapy (Nivolumab40mg) |
Eligible patients will receive 3 cycles of neoadjuvant chemotherapy(Taxane/Pemetrexed and Platinum) with low dose Immunotherapy (Nivolumab40mg). Response assessment will be done after completion of neoadjuvant
treatment followed by assessment for surgery. Patients will be assessed withCTscans every 2-3 months in the first 2 years, every 6 months for the next 3 years, andthereafter yearly for assessment of disease recurrence. Adjuvant treatment
(chemotherapy, immunotherapy, or radiotherapy) will be as per discussion inthethoracic disease management group. Patients will be followed every 2-3 months until
death for survival analysis.
Chemotherapy regimen would include a combination of Pemetrexed or Paclitaxel
with Cisplatin or Carboplatin with Nivolumab. Pemetrexed 500mg/m2 every three-weekly is administered in 100mL sodiumchloride0.9% over 10 minutes. Vitamin B12 and folic acid supplementation, anti-emeticregimen, use of dexamethasone, and growth-factor support would be givenasper
standard institutional protocol. Paclitaxel 175 mg/m2 three weekly is administered in a 500mL sodiumchloride0.9%non-PVC infusion bag with a 0.22 micron in-line filter over 3 hours. Pre-medicationsand growth-factor support would be given as per standard institutional protocol. Cisplatin will be dosed at 75 mg/m2 on day 1 of each cycle, diluted in 500ml of 0.9%normal saline (with appropriate pre- and post-chemotherapy hydration, andanti- emetic measures). Carboplatin AUC 5 (calculated by Calvert formula) will be administered intravenous,
in 250-500ml 0.9%NS or dextrose solutions over 30-60mins on Day 1. Nivolumab 40 mg would be administered in 100 ml NS over 60 minutes every3weekly. All drugs will be given IV every 3-weekly for 3 cycles followed by response
assessment. |
| Comparator Agent |
NIL |
NIL |
|
|
Inclusion Criteria
|
| Age From |
18.00 Year(s) |
| Age To |
99.00 Year(s) |
| Gender |
Both |
| Details |
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 |
|
| ExclusionCriteria |
| Details |
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
|
|
|
Method of Generating Random Sequence
|
Not Applicable |
|
Method of Concealment
|
Not Applicable |
|
Blinding/Masking
|
Not Applicable |
|
Primary Outcome
|
| Outcome |
TimePoints |
| Pathological complete response rates (pCR) |
After surgery . with 3-4 months of enrollment |
|
|
Secondary Outcome
|
| Outcome |
TimePoints |
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
|
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 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 |
|
|
Target Sample Size
|
Total Sample Size="53"
Sample Size from India="53"
Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials"
Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials" |
|
Phase of Trial
|
Phase 2 |
|
Date of First Enrollment (India)
|
24/02/2025 |
| Date of Study Completion (India) |
Applicable only for Completed/Terminated trials |
| Date of First Enrollment (Global) |
Date Missing |
| Date of Study Completion (Global) |
Applicable only for Completed/Terminated trials |
|
Estimated Duration of Trial
|
Years="3"
Months="0"
Days="0" |
|
Recruitment Status of Trial (Global)
|
Not Applicable |
| Recruitment Status of Trial (India) |
Not Yet Recruiting |
|
Publication Details
|
N/A |
|
Individual Participant Data (IPD) Sharing Statement
|
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
|
|
Brief Summary
|
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. |