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Neoadjuvant Chemotherapy and Tilelizumab in Stage III(cTNM-IIIA.IIIB)Non-small-cell Lung Cancer

Primary Purpose

Stage III, Non-small Cell Lung Cancer

Status
Unknown status
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
tislelizumab
Sponsored by
West China Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Stage III focused on measuring stage III, driver gene negative, Non-small Cell Lung Cancer

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

  1. Untreated and histologically confirmed stage III (T2N2, T3-4N1-2) NSCLC (as defined by the American Joint Committee on Cancer 8th Edition)
  2. If the driver gene negative for EGFR sensitive mutations and ALK and ROS1 gene fusion mutations has not been detected before, test specimen tissue/blood
  3. Tumor assessment scan using (CT) and (PET-CT) or magnetic resonance (MRI)
  4. The date of signing the informed consent is ≥18 years old and ≤65 years old
  5. Eastern Cooperative Oncology Group (ECOG) physical status is 0 or 1
  6. Have measurable diseases assessed by the investigator according to RECIST Version 1.1
  7. After neoadjuvant treatment, the MDT team and the chief surgeon comprehensively assessed and confirmed that they meet the requirements for radical resection
  8. After neoadjuvant therapy, evaluate once every 2 cycles. For PD, discontinue tislelizumab and receive simultaneous radiotherapy. PR/SD patients will discuss MDT and adopt surgical treatment;
  9. Good cardiopulmonary function, able to tolerate surgery
  10. Eligible to receive platinum-containing dual-drug chemotherapy
  11. Can provide representative pre-treatment tumor tissue samples/peripheral blood samples for biomarker analysis.

Exclusion Criteria:

  1. Have received any treatment for the current lung cancer, including chemotherapy or radiotherapy 1.Patients with positive driver genes are known to carry EGFR mutations or ALK, ROS1 gene translocations
  2. After neoadjuvant treatment, pneumonectomy is still required at the last evaluation
  3. Suffered from any disease requiring systemic treatment with corticosteroids (daily dose of prednisone or equivalent drugs> 10 mg) or other immunosuppressive drugs in the 14 days before enrollment
  4. Adrenaline replacement steroids (daily doses> 10 mg of prednisone or equivalent) are allowed for topical, ocular, intra-articular, intranasal or inhaled corticosteroids, and minimum systemic absorption is required, and they are prescribed Corticosteroids are short-term (≤7 days) medication, or used to treat non-autoimmune diseases
  5. A history of active autoimmune disease or autoimmune disease that may recur.
  6. Allow entry for patients with: well-controlled type I diabetes, hypothyroidism that requires only hormone replacement therapy, skin diseases that do not require systemic treatment (such as vitiligo, psoriasis, or hair loss), or predicted without external causes A disease that does not recur. The chest CT scan performed during the screening period has evidence of idiopathic pulmonary fibrosis, organic pneumonia (such as bronchiolitis obliterans), or a history of non-infectious pneumonia
  7. Severe infections occurred within 4 weeks before enrollment, including but not limited to hospitalization due to infection complications, bacteremia or severe pneumonia
  8. Severe chronic or active infections (including tuberculosis infection, etc.) that require systemic (oral or intravenous) antibiotic treatment within 14 days before enrollment
  9. A history of interstitial lung disease, non-infectious pneumonia or poorly controlled diseases, including pulmonary fibrosis, acute lung disease, etc.
  10. Untreated patients with chronic hepatitis B or HBV carriers with hepatitis B virus (HBV) DNA ≥ 500 IU/mL, or patients with active hepatitis C virus (HCV) should be excluded. Note: Inactive hepatitis B surface antigen (HBsAg) carriers, treated and stable hepatitis B carriers (HBV DNA <500 IU/mL), and cured hepatitis C patients can be included in the group.
  11. If any major surgery requiring general anesthesia has been performed ≤28 days before randomization.
  12. Previous allogeneic stem cell transplantation or organ transplantation. -

Sites / Locations

  • University

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Tilelizumab+Albumin Paclitaxel + Carboplatin/Cisplatin

Arm Description

Tilelizumab 200mg d1 Albumin Paclitaxel 260mg/m2 d1 Carboplatin/Cisplatin 75mg/m2/AUC5 d1IV,Q3W *2cycles

Outcomes

Primary Outcome Measures

Rate of radical resection (R0)
In the intention-to-treat (ITT) analysis set, the rate of radical resection (R0) is evaluated by the investigator, which is the number of people who can undergo R0 resection after the evaluation criteria established by the MDT team divided by the total number of enrolled groups

Secondary Outcome Measures

PFS
The investigator evaluated the 24-month PFS to evaluate tislelizumab combined with platinum-containing dual-drug chemotherapy as a neoadjuvant treatment, and tislelizumab was added as an adjuvant treatment

Full Information

First Posted
October 26, 2020
Last Updated
April 28, 2021
Sponsor
West China Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT04865705
Brief Title
Neoadjuvant Chemotherapy and Tilelizumab in Stage III(cTNM-IIIA.IIIB)Non-small-cell Lung Cancer
Official Title
Neoadjuvant Chemotherapy and Tilelizumab in Stage III(cTNM-IIIA.IIIB)Non-small-cell Lung Cancer ,a Single-arm, Phase Ⅱ Clinical Trial
Study Type
Interventional

2. Study Status

Record Verification Date
April 2021
Overall Recruitment Status
Unknown status
Study Start Date
November 10, 2020 (Actual)
Primary Completion Date
December 10, 2021 (Anticipated)
Study Completion Date
June 10, 2022 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
West China Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

Brief Summary
This is a prospective, one-arm, phase II study aimed at evaluating tislelizumab combined with platinum-containing dual-drug chemotherapy as a neoadjuvant treatment, supplemented with tislelizumab after surgery in patients with stage III non-small cell lung cancer.
Detailed Description
The study included a screening period, a treatment period (including neoadjuvant treatment, surgery and postoperative adjuvant treatment), and a survival follow-up period. Patients who meet the admission criteria will receive the following treatments according to disease stage (IIIA/IIIB) and histology (squamous or non-squamous) Tilelizumab + platinum-containing dual-agent chemotherapy, every 3 weeks as a cycle , for 2 cycles, followed by surgical resection, and postoperative adjuvant Tilelizumab + platinum-containing dual-agent chemotherapy 2cycles,every 3 weeks as a cycle, and Tilelizumab every 3 weeks up to 15cycles maintenance treatment. The rate of radical resection (R0) was evaluated through the research center of the investigator, which is expected to be 20% higher compared with historical controls, and the effectiveness of tislelizumab combined with platinum-containing dual-drug chemotherapy as a neoadjuvant treatment was evaluated.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Stage III, Non-small Cell Lung Cancer
Keywords
stage III, driver gene negative, Non-small Cell Lung Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
33 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Tilelizumab+Albumin Paclitaxel + Carboplatin/Cisplatin
Arm Type
Experimental
Arm Description
Tilelizumab 200mg d1 Albumin Paclitaxel 260mg/m2 d1 Carboplatin/Cisplatin 75mg/m2/AUC5 d1IV,Q3W *2cycles
Intervention Type
Drug
Intervention Name(s)
tislelizumab
Other Intervention Name(s)
Albumin Paclitaxel, Carboplatin/Cisplatin
Intervention Description
Tilelizumab 200mg d1 Q3W Albumin Paclitaxel 260mg/m2 d1 Carboplatin/Cisplatin 75mg/m2/AUC5 d1 every 3 weeks
Primary Outcome Measure Information:
Title
Rate of radical resection (R0)
Description
In the intention-to-treat (ITT) analysis set, the rate of radical resection (R0) is evaluated by the investigator, which is the number of people who can undergo R0 resection after the evaluation criteria established by the MDT team divided by the total number of enrolled groups
Time Frame
2 weeks after neoadvant
Secondary Outcome Measure Information:
Title
PFS
Description
The investigator evaluated the 24-month PFS to evaluate tislelizumab combined with platinum-containing dual-drug chemotherapy as a neoadjuvant treatment, and tislelizumab was added as an adjuvant treatment
Time Frame
up to 24-month
Other Pre-specified Outcome Measures:
Title
Biomarker level of PD-L1
Description
A PDL1 test measures the amount of PDL1 protein on cancer cells
Time Frame
2 weeks after surgery
Title
Biomarker count of CD8+T cell
Time Frame
2 weeks after surgery

10. Eligibility

Sex
All
Gender Based
Yes
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Untreated and histologically confirmed stage III (T2N2, T3-4N1-2) NSCLC (as defined by the American Joint Committee on Cancer 8th Edition) If the driver gene negative for EGFR sensitive mutations and ALK and ROS1 gene fusion mutations has not been detected before, test specimen tissue/blood Tumor assessment scan using (CT) and (PET-CT) or magnetic resonance (MRI) The date of signing the informed consent is ≥18 years old and ≤65 years old Eastern Cooperative Oncology Group (ECOG) physical status is 0 or 1 Have measurable diseases assessed by the investigator according to RECIST Version 1.1 After neoadjuvant treatment, the MDT team and the chief surgeon comprehensively assessed and confirmed that they meet the requirements for radical resection After neoadjuvant therapy, evaluate once every 2 cycles. For PD, discontinue tislelizumab and receive simultaneous radiotherapy. PR/SD patients will discuss MDT and adopt surgical treatment; Good cardiopulmonary function, able to tolerate surgery Eligible to receive platinum-containing dual-drug chemotherapy Can provide representative pre-treatment tumor tissue samples/peripheral blood samples for biomarker analysis. Exclusion Criteria: Have received any treatment for the current lung cancer, including chemotherapy or radiotherapy 1.Patients with positive driver genes are known to carry EGFR mutations or ALK, ROS1 gene translocations After neoadjuvant treatment, pneumonectomy is still required at the last evaluation Suffered from any disease requiring systemic treatment with corticosteroids (daily dose of prednisone or equivalent drugs> 10 mg) or other immunosuppressive drugs in the 14 days before enrollment Adrenaline replacement steroids (daily doses> 10 mg of prednisone or equivalent) are allowed for topical, ocular, intra-articular, intranasal or inhaled corticosteroids, and minimum systemic absorption is required, and they are prescribed Corticosteroids are short-term (≤7 days) medication, or used to treat non-autoimmune diseases A history of active autoimmune disease or autoimmune disease that may recur. Allow entry for patients with: well-controlled type I diabetes, hypothyroidism that requires only hormone replacement therapy, skin diseases that do not require systemic treatment (such as vitiligo, psoriasis, or hair loss), or predicted without external causes A disease that does not recur. The chest CT scan performed during the screening period has evidence of idiopathic pulmonary fibrosis, organic pneumonia (such as bronchiolitis obliterans), or a history of non-infectious pneumonia Severe infections occurred within 4 weeks before enrollment, including but not limited to hospitalization due to infection complications, bacteremia or severe pneumonia Severe chronic or active infections (including tuberculosis infection, etc.) that require systemic (oral or intravenous) antibiotic treatment within 14 days before enrollment A history of interstitial lung disease, non-infectious pneumonia or poorly controlled diseases, including pulmonary fibrosis, acute lung disease, etc. Untreated patients with chronic hepatitis B or HBV carriers with hepatitis B virus (HBV) DNA ≥ 500 IU/mL, or patients with active hepatitis C virus (HCV) should be excluded. Note: Inactive hepatitis B surface antigen (HBsAg) carriers, treated and stable hepatitis B carriers (HBV DNA <500 IU/mL), and cured hepatitis C patients can be included in the group. If any major surgery requiring general anesthesia has been performed ≤28 days before randomization. Previous allogeneic stem cell transplantation or organ transplantation. -
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
yongseng wang
Organizational Affiliation
West China Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
qinghua zhou
Organizational Affiliation
West China Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
University
City
Chengdu
State/Province
Sichuan
ZIP/Postal Code
610041
Country
China

12. IPD Sharing Statement

Plan to Share IPD
Undecided

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Neoadjuvant Chemotherapy and Tilelizumab in Stage III(cTNM-IIIA.IIIB)Non-small-cell Lung Cancer

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