Efficacy Analysis of Neoadjuvant Treatment in Lung Cancer Using Low-dose Nivolumab Combined With Chemotherapy

Efficacy Analysis of Neoadjuvant Treatment in Lung Cancer Using Low-Dose Nivolumab Combined With Chemotherapy

The primary objective of this study is to assess the major pathological response (MPR) rate and pathologic complete response (pCR) rate in stage IB-IIIA non-small cell lung cancer (NSCLC) treated with a low dose of neoadjuvant immunotherapy combined with platinum doublet.

Study Overview

• Status: Recruiting
• Conditions: Lung Cancer, Nonsmall Cell; Non-Small Cell Lung Cancer NSCLC
• Intervention / Treatment: Drug: Low-dose nivolumab combined with platinum-based doublet chemotherapy

• Study Type: Interventional
• Enrollment (Estimated): 33
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: JOAO A SOLER, MD; Phone Number: +55 17 981350180; Email: joao.soler@hbonco.org.br
• Study Contact Backup: Name: ALINE FARES, MD; Email: aline.fares@edu.famerp.br

Study Locations

• Brazil
  • SAO Paulo
    • Sao Jose Do Rio Preto, SAO Paulo, Brazil, 15090000
      • Recruiting
      • Fundação Faculdade Regional de Medicina de São José do Rio Preto

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Able to provide a signed Informed Consent Form (ICF), indicating agreement to comply with the requirements and restrictions in the ICF and protocol.
• Male or female, aged 18 years or older.
• Diagnosed with non-small cell lung cancer (NSCLC) with clinical staging IB, II, or IIIA.
• Receiving treatment at Hospital de Base.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at enrollment, with no decline from two weeks prior to the baseline period or the day of the first dose.
• Tumor sample meets the following requirements:
• Negative for EGFR gene expression.
• Negative for ALK and ROS1 protein expression.
• PD-L1 protein expression documented and assessable.
• Tumor is considered resectable upon initial assessment by three thoracic oncology surgeons (IR, CM, and HN) following a multidisciplinary review.
• Adequate organ and bone marrow function as defined below:
• Hemoglobin: ≥ 9.0 g/dL*
• Absolute neutrophil count: ≥ 1.5 × 10^9 /L*
• Platelet count: ≥ 100 × 10^9 /L*
• *Note: Granulocyte colony-stimulating factor (G-CSF), platelet transfusions, and blood transfusions are not permitted to meet these values.
• Serum bilirubin: ≤ 1.5 × upper limit of normal (ULN), except for participants with confirmed Gilbert syndrome, who may be included upon physician consultation.
• ALT and AST: ≤ 2.5 × ULN.
• Creatinine clearance: ≥ 50 mL/min (calculated using the Cockcroft and Gault formula).
• Life expectancy greater than six months prior to randomization.

Exclusion Criteria:

• Refusal to sign the Informed Consent Form (ICF).
• NSCLC clinical stages IA, IIIB N3, IIIC, IVA, and IVB.
• Tumors with T4 invasion of the aorta, esophagus, and/or heart; or presence of bulky N2 disease.
• Tumor deemed unresectable.
• Prior systemic anticancer therapy for NSCLC, including chemotherapy, biologic therapy, immunotherapy, or any investigational drugs.
• History of another primary malignancy, with exceptions for:
• Malignancies treated with curative intent and no active disease for ≥ 2 years before the first dose of investigational product (IP) and with a low risk of recurrence.
• Adequately treated non-melanoma skin cancer or lentigo maligna with no evidence of disease.
• Adequately treated carcinoma in situ with no evidence of disease.
• Incomplete basic medical information in the electronic medical record.
• Positive for EGFR gene expression.
• Positive for ALK protein expression.
• No available data on PD-L1 protein expression.
• Positive for ROS1 protein expression.
• Pregnant or breastfeeding at the time of enrollment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Low-dose nivolumab combined with platinum-based doublet chemotherapy	Drug: Low-dose nivolumab combined with platinum-based doublet chemotherapy; Platinum-based neoadjuvant chemotherapy (carboplatin at AUC 5 or 6 combined with either paclitaxel at 175 mg/m² or pemetrexed at 500 mg/m²), administered with nivolumab at 0.3 mg/kg every 21 days for 3 cycles.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Major Pathologic Response	MPR is defined as the proportion of participants who have achieved major pathologic response (on routine hematoxylin and eosin staining, tumors with no more than 10% viable tumor cells) in all participants who have completed the neoadjuvant therapy before surgery.	2-3 months
Pathologic Complete Response	Pathological complete response (pCR) is defined as having no residual cancer at the primary site or in regional lymph nodes on pathologic review of the surgical specimen.	2-3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse Events	TRAE is defined and classified according to NCI-CTCAE v5.0 in all participants.	Up to 3 months after the end of treatment
Event-Free-Survival	Event-free survival (EFS) is defined as the length of time (months) from randomization to any of the following events: any progression of disease precluding surgery, progression or recurrence disease based on response evaluation criteria in solid tumors (RECIST) 1.1 after surgery, or death due to any cause. Participants who don't undergo surgery for reason other than progression will be considered to have an event at progression or death.	Up to 60 months
R0 resection	R0 resection rate is defined as the proportion of participants who have achieved R0 resection (complete resection with no residual tumor cell in the resection margin) in all participants.	Up to 3 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of conversion from minimally invasive surgery to open surgery	The frequency at which a minimally invasive procedure needs to be converted to an open surgical approach mid-operation	2-3 months

Collaborators and Investigators

• Sponsor: Aline Fusco Fares, MD
• Collaborators: Hospital de Base de Sao Jose do Rio Preto
• Investigators: Principal Investigator: JOAO A SOLER, MD, Fundação Faculdade Regional de Medicina de São José do Rio Preto

Study record dates

Study Major Dates

• Study Start (Actual): October 10, 2023
• Primary Completion (Estimated): October 31, 2025
• Study Completion (Estimated): October 31, 2027

Study Registration Dates

• First Submitted: June 6, 2024
• First Submitted That Met QC Criteria: October 29, 2024
• First Posted (Actual): October 31, 2024

Study Record Updates

• Last Update Posted (Actual): October 31, 2024
• Last Update Submitted That Met QC Criteria: October 29, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Keywords: Neoadjuvant immunotherapy; Low Dose Immunotherapy; Non-Small-Cell-Lung-Cancer
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Nivolumab
• Other Study ID Numbers: LungCancerLowDose

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes