Clinical Study of Neoadjuvant Chemotherapy and Immunotherapy Combined With Probiotics in Patients With Resectable NSCLC

Clinical Study of Neoadjuvant Chemotherapy and Immunotherapy Combined With Probiotics in Patients With Resectable Non-small Cell Lung Cancer

To evaluate the safety and effect of neoadjuvant chemotherapy and immunotherapy combined with probiotics for early resectable NSCLC patients.

Study Overview

• Status: Active, not recruiting
• Conditions: Non-small Cell Lung Cancer Stage IIIB; Non-small Cell Lung Cancer Stage II; Non-small Cell Lung Cancer Stage ⅢA
• Intervention / Treatment: Drug: nivolumab 4.5mg/kg+Paclitaxel (albumin-bound type) 260mg / m2+ Carboplatin AUC5

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Hunan
    • Changsha, Hunan, China, 410008
      • Xiangya Hospital of Central South University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Histologically or cytologically confirmed previously untreated non-small cell lung cancer. Patients with stage II, IIIA and potentially resectable stage IIIB (T3N2) disease (according to AJCC 8th edition) are eligible ;
• Eastern Cooperative Oncology Group (ECOG) performance status score 0-1;
• 18 years ≤ Age ≤ 80 years. Signed and dated written informed consent must be provided by the patient prior to admission to the study;
• Patients with appropriate treatment compliance and could be followed-up correctly;
• Patients with measurable or evaluable diseases (according to RECIST 1.1);
• Patients must have the ability to swallow oral drugs;
• Patients with adequate pulmonary function capable of tolerating the proposed lung resection (as determined by the surgeon);
• Signed and dated written informed consent must be provided by the patient prior to admission to the study.

Exclusion Criteria:

• Subjects with known ALK translocations or EGFR mutations.
• Subjects with active, known or suspected autoimmune disease. Subjects with 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 are permitted to enroll;
• Subjects with 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;
• Patients with symptomatic ILD (grade 3-4) and/or poor lung function and a history of interstitial lung disease cannot be included. If you have any questions, please contact the trial team;
• Patients with other active malignant tumors currently receiving cancer therapy (chemotherapy, radiation therapy, immunotherapy, or biologic therapy) or investigational anti-cancer drug;
• Patients who are inability to follow the procedures required in the protocol due to any medical, mental or psychological conditions;
• Prior treatment with an anti-PD-1, anti-PD-L1 or anti-CTLA-4 antibody or any other antibodies or drugs that target T cell costimulation or immune checkpoint pathways;
• Known positive test for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid indicating acute or chronic infection;
• Known history of testing positive for human immunodeficiency virus or known acquired immunodeficiency syndrome;
• Patients with a history of allergy to study drugs or ingredients.

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: Arm 1; 3 cycles of nivolumab+Paclitaxel (albumin-bound type)+ Carboplatin AUC5 (21 days/cycle); as well as BiFico (oral taking, 4 capsules/time, 2 times per day)	Drug: nivolumab 4.5mg/kg+Paclitaxel (albumin-bound type) 260mg / m2+ Carboplatin AUC5; 3 cycles of nivolumab+Paclitaxel (albumin-bound type)+ Carboplatin AUC5 (21 days/cycle); as well as BiFico (oral taking, 4 capsules/time, 2 times per day); Other Names: Bifidobacterium trifidum live powder (BiFico, SINE)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pathological complete response	The percentage of participants with 0% residual viable tumor cells in the primary tumor and sampled lymph nodes after neoadjuvant therapy, as assessed by a blinded independent pathological review.	Within 3 days after the operation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate	The percentage of participants who achieved complete response or partial response after 3 cycles of neoadjuvant therapy according to the RECIST 1.1 criteria.	28 days after the completion of three cycles of neoadjuvant therapy and before the operation
Major Pathologic Response	The percentage of participants with no more than 10% residual viable tumor cells in the primary tumor and sampled lymph nodes after neoadjuvant therapy, as assessed by a blinded independent pathological review.	Within 3 days after the operation
Disease free survival	The time (month) from the completion of lung cancer radical surgery to the recurrence or metastasis of the disease.	1 year, 3 years and 5 years after the operation
Recurrence rate	The percentage of participants who have recurrence or metastasis of lung cancer at certain time points after radical surgery.	1 year, 3 years and 5 years after the operation
Overall survival	The time (month) from the completion of lung cancer radical surgery to all-cause death.	1 year, 3 years and 5 years after the operation
Adverse effects	The number of participants with treatment-related adverse events as assessed by CTCAE v5.0.	Treatment-related adverse events were assessed between the first neoadjuvant dose and 30 days after the last dose of neoadjuvant study treatment.
Surgical complications (intra-operative and peri-operative)	The number of participants with surgery-related adverse events that occur during or after a surgical procedure.	90 days after the first medication or 30 days after the operation, whichever is later
R0 surgical events	The number of participants who have lung cancer completely resected. It is defined as the removal of negative margins, encompassing bronchial, arterial, venous peribronchial, and surrounding tissues near the tumor. In addition, at least 6 groups of lymph nodes must be removed, including at least 3 groups of intrapulmonary lymph nodes and 3 groups of mediastinal lymph nodes (station 7 lymph node must be included). The resected lymph nodes should be negative upon microscopic examination.	28 days after the completion of three cycles of neoadjuvant therapy
Clinical TNM downstaging	The number of participants who achieve a decrease in the clinical TNM stage of lung cancer following neoadjuvant therapy before surgery.	28 days after the completion of three cycles of neoadjuvant therapy and before the operation

Collaborators and Investigators

• Sponsor: Xiangya Hospital of Central South University
• Investigators: Study Director: Yang Gao, Doctor, Xiangya Hospital of Central South University

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2020
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: December 27, 2020
• First Submitted That Met QC Criteria: January 5, 2021
• First Posted (Actual): January 7, 2021

Study Record Updates

• Last Update Posted (Estimated): November 22, 2024
• Last Update Submitted That Met QC Criteria: November 21, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• 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; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Nivolumab; Carboplatin; Paclitaxel
• Other Study ID Numbers: 202007093

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: all IPD that underlie results in a publication
• IPD Sharing Time Frame: IPD will be shared when the clinical trail is finished
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

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