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The Effect of Toripalimab Plus Radiotherapy in Patients With Operable Stage II-IIIA (N+) Non Small Cell Lung Cancer

Primary Purpose

NSCLC

Status
Recruiting
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
SBRT+LDRT
Toripalimab
Chemotherapy drug
Toripalimab
Sponsored by
Shanghai Chest Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for NSCLC focused on measuring neoadjuvant immunotherapy, radiotherapy

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Age 18 to 75 years old, gender is not limited. ECOG performance status 0-1. non-small cell lung cancer diagnosed by pathology. sufficient tumor tissue available for biomarker analysis. clinical staging of cT1-2N1-2M0 or T3N1M0, stage II-IIIA (8th UICC staging criteria). Patients with distant metastases ruled out by CT or PET/CT and physically assessed as acceptable for radical lung cancer surgery. histomolecular pathology confirming the absence of classic driver oncogene mutations in EGFR, ALK, or ROS1. Basic normal function of all organs (laboratory test results within 1 week prior to enrollment). Bone marrow function: absolute neutrophil count (ANC) ≥ 1.5x109 /L, platelet count ≥ 100x109 /L, hemoglobin ≥ 9g/dL. Liver: serum total bilirubin ≤ 1.5 times the upper limit of normal; ALT and AST ≤ 2.5 times the upper limit of normal. Kidney: blood creatinine level ≤ 1.5 times the upper limit of normal or creatinine clearance ≥ 60 ml/min and urea nitrogen ≤ 200 mg/L. Urine protein <+, if urine protein + then total 24 hour protein must be <500mg. Blood glucose: within normal range and/or with diabetic patients on treatment but with stable blood glucose control. Pulmonary function: baseline FEV1 of at least 2L; if baseline FEV1 < 2L then FEV1 > 800ml is expected after surgery as assessed by a surgical specialist. Cardiac function: no myocardial infarction within 1 year; no unstable angina; no symptomatic severe arrhythmia; no cardiac insufficiency. Voluntarily participated in this study and signed the informed consent form by himself or his agent Exclusion Criteria: Pathology suggestive of compound small cell lung cancer, etc. History of previous lobectomy, radiotherapy or chemotherapy. Those with concurrent second primary carcinoma and a history of previous malignancy of less than 5 years (except for completely cured cervical carcinoma in situ or basal cell or squamous epithelial cell skin cancer). Patients with any active autoimmune disease or a history of autoimmune disease (e.g., interstitial pneumonia, uveitis, enterocolitis, hepatitis, pituitary inflammation, vasculitis, myocarditis, nephritis, hyperthyroidism, hypothyroidism, etc.). Have an active infection requiring systemic treatment or a history of active tuberculosis. Known history of human immunodeficiency virus (HIV) or active chronic Hepatitis C or Hepatitis B virus infection or any uncontrolled active systemic infection requiring intravenous (iv) antimicrobial treatment. Those with known presence or coexistence of other uncontrollable diseases that are not amenable to surgical treatment Physical examination or clinical trial finds that, in the opinion of the investigator, may interfere with the results or place the patient at increased risk for treatment complications Prior interstitial lung disease, drug-induced interstitial disease or any clinically evident active interstitial lung disease with idiopathic pulmonary fibrosis on baseline CT scan; uncontrolled massive pleural or pericardial effusion Unstable systemic concomitant disease (active infection, moderate to severe chronic obstructive pulmonary disease, poorly controlled hypertensive disease, unstable angina pectoris, congestive heart failure, myocardial infarction occurring within 6 months, severe mental disorder requiring medication for control, liver, renal or other metabolic disease, neuropsychiatric pathology such as Alzheimer's disease) History of congenital or acquired immunodeficiency disorders or organ transplantation Received any of the following treatments: Prior radiotherapy, treatment with anti PD-1, anti PD-L1 or anti PD-L2 drugs, or other drugs that synergistically inhibit T-cell receptors such as CTLA-4, OX-40, CD137. Having received any investigational drug within 4 weeks Concurrent enrollment in another clinical study, unless it is an observational (non-interventional) clinical study or an interventional clinical study follow-up Persons who have received an antineoplastic vaccine or who have received a live vaccine within 4 weeks Have undergone major surgery or had severe trauma within 4 weeks

Sites / Locations

  • Shanghai Chest HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Experimental: Arm A

Conrol: Arm B

Arm Description

Radiation: primary tumor SBRT, DT: 24Gy/3Fx, d1-3, d22-24; positive lymph nodes LDRT, DT: 2Gy/4Fx, d1-4, d22-25 (2 cycles) ; Drug: toripalimab 240mg ivgtt d5, d26 (2 cycles)

Drug: Chemotherapy + toripalimab 240mg ivgtt d1, d22 (2 cycles) Chemotherapy regimen: Non-squamous carcinoma: pemetrexed + platinum or paclitaxel + platinum. Squamous carcinoma: paclitaxel + platinum or gemcitabine + platinum

Outcomes

Primary Outcome Measures

Pathlogical complete remission (pCR) rate
Pathlogical complete remission rate

Secondary Outcome Measures

major pathologic response (MPR) of primary tumor
proportion of residual tumor ≤10%
Perioperative complications
complications occurring during operation
Completion of surgery
whether the surgery is completed
Rate of R0 resection
rate of participants with tumor margin negative
treatment emergent adverse event (TEAE)
number of participants who have adverse events occurring during the treatment period
Event-free survival (EFS)
Event-free survival
Overall survival (OS)
Overall survival
circulating tumor DNA (ctDNA)
the expression of circulating tumor DNA
Immune subtypes
the tumor immune microenvironment subtype according to PD-L1 and tumor-infiltrating lymphocytes
PD-L1 expression
the status of PD-L1
Tumor mutation burden (TMB)
frequency of tumor gene mutation

Full Information

First Posted
January 18, 2023
Last Updated
April 2, 2023
Sponsor
Shanghai Chest Hospital
Collaborators
Shanghai Junshi Bioscience Co., Ltd.
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1. Study Identification

Unique Protocol Identification Number
NCT05798845
Brief Title
The Effect of Toripalimab Plus Radiotherapy in Patients With Operable Stage II-IIIA (N+) Non Small Cell Lung Cancer
Official Title
Exploratory Phase II Clinical Study of Toripalimab Plus Radiotherapy Versus Toripalimab Plus Chemotherapy for the Neoadjuvant Treatment of Operable Stage II-IIIA (N+) Non-small Cell Lung Cancer (NSCLC)
Study Type
Interventional

2. Study Status

Record Verification Date
April 2023
Overall Recruitment Status
Recruiting
Study Start Date
February 20, 2023 (Actual)
Primary Completion Date
February 2024 (Anticipated)
Study Completion Date
February 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Shanghai Chest Hospital
Collaborators
Shanghai Junshi Bioscience Co., Ltd.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This randomized phase II trial is to explore the clinical efficacy, safety and feasibility of neoadjuvant immunotherapy plus radiotherapy compared with neoadjuvant immunotherapy plus chemotherapy in operable stage II-IIIA (N+) non small cell lung cancer (NSCLC) and the optimal radiotherapy pattern.
Detailed Description
In recent years, the survival rate after diagnosis of non small cell lung cancer (NSCLC) has improved with advances in treatment. In terms of 5-year average overall survival (OS) by stage at the time of diagnosis, OS decreases significantly from stage IB to IIIA NSCLC, with 68% for stage IB, 53-60% for stage II, and 36% for stage IIIA. How to optimize the perioperative treatment strategy to reduce postoperative recurrence and prolong the survival of patients has raised great concern in early and mid-stage NSCLC. Radiotherapy combined with immunotherapy is suggested for advanced NSCLC in preclinical basic studies and recent clinical trials. Stereotactic body radiation therapy (SBRT) at 8 Gy × 3 Fx plays an effective immunoregulated role and can further enhance the antitumor immune response promoted by immune checkpoint inhibitors (ICIs). Although little is known about the optimal SBRT dose and fraction pattern, 6 Gy × 5 Fx or 8-9 Gy × 3 Fx have shown effectiveness in clinical studies.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
NSCLC
Keywords
neoadjuvant immunotherapy, radiotherapy

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
124 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Experimental: Arm A
Arm Type
Experimental
Arm Description
Radiation: primary tumor SBRT, DT: 24Gy/3Fx, d1-3, d22-24; positive lymph nodes LDRT, DT: 2Gy/4Fx, d1-4, d22-25 (2 cycles) ; Drug: toripalimab 240mg ivgtt d5, d26 (2 cycles)
Arm Title
Conrol: Arm B
Arm Type
Active Comparator
Arm Description
Drug: Chemotherapy + toripalimab 240mg ivgtt d1, d22 (2 cycles) Chemotherapy regimen: Non-squamous carcinoma: pemetrexed + platinum or paclitaxel + platinum. Squamous carcinoma: paclitaxel + platinum or gemcitabine + platinum
Intervention Type
Radiation
Intervention Name(s)
SBRT+LDRT
Intervention Description
primary tumor SBRT, DT: 24Gy/3Fx, d1-3, d22-24; positive lymph nodes LDRT, DT: 2Gy/4Fx, d1-4, d22-25 (2 cycles)
Intervention Type
Drug
Intervention Name(s)
Toripalimab
Intervention Description
toripalimab 240mg ivgtt d5, d26 (2 cycles)
Intervention Type
Drug
Intervention Name(s)
Chemotherapy drug
Intervention Description
Non-squamous carcinoma: pemetrexed + platinum or paclitaxel + platinum Squamous carcinoma: paclitaxel + platinum or gemcitabine + platinum
Intervention Type
Drug
Intervention Name(s)
Toripalimab
Intervention Description
toripalimab 240mg ivgtt d1, d22 (2 cycles)
Primary Outcome Measure Information:
Title
Pathlogical complete remission (pCR) rate
Description
Pathlogical complete remission rate
Time Frame
1 year
Secondary Outcome Measure Information:
Title
major pathologic response (MPR) of primary tumor
Description
proportion of residual tumor ≤10%
Time Frame
1 year
Title
Perioperative complications
Description
complications occurring during operation
Time Frame
1 year
Title
Completion of surgery
Description
whether the surgery is completed
Time Frame
intraoperative
Title
Rate of R0 resection
Description
rate of participants with tumor margin negative
Time Frame
1 year
Title
treatment emergent adverse event (TEAE)
Description
number of participants who have adverse events occurring during the treatment period
Time Frame
1 year
Title
Event-free survival (EFS)
Description
Event-free survival
Time Frame
3 years
Title
Overall survival (OS)
Description
Overall survival
Time Frame
3 years
Title
circulating tumor DNA (ctDNA)
Description
the expression of circulating tumor DNA
Time Frame
1 year
Title
Immune subtypes
Description
the tumor immune microenvironment subtype according to PD-L1 and tumor-infiltrating lymphocytes
Time Frame
1 year
Title
PD-L1 expression
Description
the status of PD-L1
Time Frame
1 year
Title
Tumor mutation burden (TMB)
Description
frequency of tumor gene mutation
Time Frame
1 year

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Age 18 to 75 years old, gender is not limited. ECOG performance status 0-1. non-small cell lung cancer diagnosed by pathology. sufficient tumor tissue available for biomarker analysis. clinical staging of cT1-2N1-2M0 or T3N1M0, stage II-IIIA (8th UICC staging criteria). Patients with distant metastases ruled out by CT or PET/CT and physically assessed as acceptable for radical lung cancer surgery. histomolecular pathology confirming the absence of classic driver oncogene mutations in EGFR, ALK, or ROS1. Basic normal function of all organs (laboratory test results within 1 week prior to enrollment). Bone marrow function: absolute neutrophil count (ANC) ≥ 1.5x109 /L, platelet count ≥ 100x109 /L, hemoglobin ≥ 9g/dL. Liver: serum total bilirubin ≤ 1.5 times the upper limit of normal; ALT and AST ≤ 2.5 times the upper limit of normal. Kidney: blood creatinine level ≤ 1.5 times the upper limit of normal or creatinine clearance ≥ 60 ml/min and urea nitrogen ≤ 200 mg/L. Urine protein <+, if urine protein + then total 24 hour protein must be <500mg. Blood glucose: within normal range and/or with diabetic patients on treatment but with stable blood glucose control. Pulmonary function: baseline FEV1 of at least 2L; if baseline FEV1 < 2L then FEV1 > 800ml is expected after surgery as assessed by a surgical specialist. Cardiac function: no myocardial infarction within 1 year; no unstable angina; no symptomatic severe arrhythmia; no cardiac insufficiency. Voluntarily participated in this study and signed the informed consent form by himself or his agent Exclusion Criteria: Pathology suggestive of compound small cell lung cancer, etc. History of previous lobectomy, radiotherapy or chemotherapy. Those with concurrent second primary carcinoma and a history of previous malignancy of less than 5 years (except for completely cured cervical carcinoma in situ or basal cell or squamous epithelial cell skin cancer). Patients with any active autoimmune disease or a history of autoimmune disease (e.g., interstitial pneumonia, uveitis, enterocolitis, hepatitis, pituitary inflammation, vasculitis, myocarditis, nephritis, hyperthyroidism, hypothyroidism, etc.). Have an active infection requiring systemic treatment or a history of active tuberculosis. Known history of human immunodeficiency virus (HIV) or active chronic Hepatitis C or Hepatitis B virus infection or any uncontrolled active systemic infection requiring intravenous (iv) antimicrobial treatment. Those with known presence or coexistence of other uncontrollable diseases that are not amenable to surgical treatment Physical examination or clinical trial finds that, in the opinion of the investigator, may interfere with the results or place the patient at increased risk for treatment complications Prior interstitial lung disease, drug-induced interstitial disease or any clinically evident active interstitial lung disease with idiopathic pulmonary fibrosis on baseline CT scan; uncontrolled massive pleural or pericardial effusion Unstable systemic concomitant disease (active infection, moderate to severe chronic obstructive pulmonary disease, poorly controlled hypertensive disease, unstable angina pectoris, congestive heart failure, myocardial infarction occurring within 6 months, severe mental disorder requiring medication for control, liver, renal or other metabolic disease, neuropsychiatric pathology such as Alzheimer's disease) History of congenital or acquired immunodeficiency disorders or organ transplantation Received any of the following treatments: Prior radiotherapy, treatment with anti PD-1, anti PD-L1 or anti PD-L2 drugs, or other drugs that synergistically inhibit T-cell receptors such as CTLA-4, OX-40, CD137. Having received any investigational drug within 4 weeks Concurrent enrollment in another clinical study, unless it is an observational (non-interventional) clinical study or an interventional clinical study follow-up Persons who have received an antineoplastic vaccine or who have received a live vaccine within 4 weeks Have undergone major surgery or had severe trauma within 4 weeks
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Xiaolong Fu, MD
Phone
862122200000
Ext
3202
Email
xlfu1964@126.com
First Name & Middle Initial & Last Name or Official Title & Degree
Wen Feng, MD
Phone
862122200000
Ext
3203
Email
fengwen412@126.com
Facility Information:
Facility Name
Shanghai Chest Hospital
City
Shanghai
State/Province
Shanghai
ZIP/Postal Code
200030
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Xiaolong Fu, MD
Phone
021-22200000
Ext
3202
First Name & Middle Initial & Last Name & Degree
Xiaolong Fu
First Name & Middle Initial & Last Name & Degree
Wentao Fang

12. IPD Sharing Statement

Plan to Share IPD
No
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The Effect of Toripalimab Plus Radiotherapy in Patients With Operable Stage II-IIIA (N+) Non Small Cell Lung Cancer

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