Trial Title:
Tislelizumab Combined With Recombinant Human Endostatin Combined With Chemotherapy for Unresectable Stage III Non-small Cell Lung Cancer.
NCT ID:
NCT06617936
Condition:
Unresectable Non-small Cell Lung Cancer
Conditions: Official terms:
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Tislelizumab
Endostar protein
Endostatins
Conditions: Keywords:
neoadjuvant therapy
NSCLC
immunotherapy
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
neoadjuvant therapy:Tislelizumab With Recombinant human endostatin combined with Chemotherapy
Description:
neoadjuvant therapy : Tislelizumab: 200mg, ivgtt, day 1 ; Recombinant Human Endostatin
Injection (Endostar),210mg was pumped intravenously for 3 consecutive days; Pemetrexed
(Non-squamous NSCLC) or Nab-paclitaxel(Squamous NSCLC):Pemetrexed: 500 mg/m^2, ivgtt, day
1. Nab-paclitaxel: 260mg/m^2, ivgtt, day 1.; Carboplatin:Carboplatin was given dosed to
an area under the serum concentration-time curve (AUC) of 5 ivgtt on day 1 ; every 21
days for 1 cycle,2-4 cycles; (If the preoperative neoadjuvant did not reach 4 cycles, the
treatment with ralizumab combined with recombinant human endostatin injection and
chemotherapy for 1-2 cycles can be continued after surgery, and the total cycle of
chemotherapy before and after surgery is up to 4 cycles)
Arm group label:
Participant Group/Arm A
Arm group label:
Participant Group/Arm B
Intervention type:
Procedure
Intervention name:
surgery
Description:
Patients who are discussed by the MDT panel to evaluate surgical resection will undergo
surgery.Surgery must be done within the 4th-6th week from day 1 the last cycle of
neoadjuvant treatment.
Arm group label:
Participant Group/Arm A
Intervention type:
Drug
Intervention name:
Adjuvant therapy:Tislelizumab and Recombinant Human Endostatin Injection (Endostar)
Description:
Adjuvant therapy Tislelizumab: 200mg, ivgtt, day 1 of each 21-day cycle, 17 cycles at
most. Recombinant Human Endostatin Injection (Endostar):210mg was pumped intravenously
for 3 consecutive days, every 21 days for 1 cycle,17 cycles at most.
Arm group label:
Participant Group/Arm A
Intervention type:
Other
Intervention name:
Standard Treatment
Description:
Patients assessed by the MDT panel as inoperable for surgical treatment will be selected
by the investigator for a standard treatment protocol determined by the MDT discussion
Arm group label:
Participant Group/Arm B
Summary:
This is a prospective, single-arm, multicenter, phase II clinical study designed to
evaluate the initial efficacy and safety of patients receiving Tislelizumab in
combination with recombinant human endostatin injection plus chemotherapy for stage III
unresectable non-small cell lung cancer. To evaluate the surgical conversion rate of
tirellizumab combined with recombinant human endostatin injection and chemotherapy
induction therapy in patients with initially unresectable stage III non-small cell lung
cancer.
Criteria for eligibility:
Criteria:
1. Have fully understood the study and voluntarily signed the informed consent;
2. Age 18-75 years old, gender is not limited;
3. Histologically confirmed Stage III initial unresectable squamous or non-squamous
non-small cell lung cancer (AJCC Stage 8th edition)
- Unresectable stage III NSCLC mainly refers to imaging or lymph node
pathological evidence: Multiple metastases of ipsilateral mediastinal lymph
nodes fused into masses or multisite metastases (IIIA: T1-2N2 or IIIB: T3-4N2);
metastases to the contralateral hilar, mediastinal lymph nodes, or to the same,
contralateral scalene, or supraclavicular lymph nodes (IIIB: T1-2N3, IIIC:
T3-4N3); lesion invasion of important organs (including diaphragm, mediastinum,
great blood vessels, trachea, recurrent laryngeal nerve, esophagus, or
satellite nodules in different pulmonary lobes on the same side of the primary
tumor, resulting in clinician determination that R0 resection could not be
performed) (IIIA: T4N0-1); Determination of o N2/N3 lymph node involvement:
PET-CT was used to confirm lymph node status. In cases where PET-CT is
insufficient to determine lymph node staging (for example, lymph node diameter
<2cm), pathologic confirmation (EBUS/EUS/
thoracoscopic/mediastinoscopy or fine needle aspiration biopsy) is performed by
the investigator to select appropriate lymph nodes to determine the staging.
Clinical evaluation of unresectable Stage III NSCLC: Other clinicians determine that
R0 resection is not feasible or that a total lung resection is required to achieve
R0 resection.
4. At least 1 measurable lesion as defined by RECIST v1.1;
5. ECOG score 0-1;
6. Eligible for platinum-containing double-drug chemotherapy.
7. Good organ function;
• Patients have not received blood transfusion or growth factor support therapy ≤ 14
days prior to sample collection during the screening period and: Absolute neutral
cell count (ANC) ≥1.5 x 109/L
- Platelet ≥100 x 109/L
- Hemoglobin ≥90 g/L
• Calculated creatinine clearance (CrCl) (Cockcroft-Gault formula)
- Patients scheduled to receive cisplatin: creatinine clearance ≥ 60 mL/min
- Patients scheduled to receive carboplatin: creatinine clearance ≥ 45 mL/min
- Serum total bilirubin ≤1.5 × upper limit of normal (ULN) (patients with
Gilbert's syndrome must have total bilirubin < 3 ×
ULN)
- AST and ALT≤ 2.5 x ULN
- Patients who did not receive anticoagulant therapy: International
standardized ratio or activated partial thromboplastin time ≤ 1.5 × ULN
- Albumin ≥25 g/L (2.5 g/dL).
8. Willing and able to comply with study plan visits, treatment plans, laboratory tests
and other study procedures;
9. The total amount of lung function, as assessed by the surgeon, is sufficient to
withstand the proposed pneumonectomy;
10. Women of childbearing age must take a serum pregnancy test within 3 days before the
first medication, and the result is negative. Female subjects of reproductive age
and male subjects whose partners are women of reproductive age must agree to use
highly effective methods of contraception during the study period and for 120 days
after the last dose of the study drug
Exclusion Criteria:
1. Patients with known EGFR gene mutation, ALK rearrangement, ROS-1 fusion, RET fusion,
HER-2 mutation, MET mutation, and non-squamous cell carcinoma with unknown driver
gene status;
2. Previous treatment for current lung cancer, including radiotherapy and all systemic
antitumor agents, including chemotherapy, immunotherapy, targeted therapy or
antiangiogenic therapy.
3. Patients with large cell neuroendocrine carcinoma (LCNEC) components and non-small
cell lung cancer with mixed small cell components.
4. Patients received other approved systemic immunomodulators (including, but not
limited to, interferon, interleukin 2, tumor necrosis factor, thymus pentapeptide,
and thymofasin) within 4 weeks prior to initial administration.
5. In the course of treatment, researchers determined that patients' tumors
were more likely to invade important blood vessels and cause fatal bleeding.
6. Clinically significant hemoptysis (more than 50ml of hemoptysis per day), or
clinically significant bleeding symptoms or significant bleeding tendency (such as
gastrointestinal bleeding, gastric ulcer bleeding, gastrointestinal bleeding,
hemorrhagic gastric ulcer, fecal occulted blood ++ or above baseline, or vasculitis)
within 3 months before the study.
7. Any Chinese herbs used for cancer control were used within 14 days prior to the
first administration of the study drug.
8. Have received live vaccine within 30 days before the first dose. Including but not
limited to the following: mumps, rubella, measles, varicella/shingles (chickenpox),
yellow fever, rabies, BCG and typhoid vaccine (inactivated virus vaccine allowed);
Live or attenuated vaccine is expected to be required during the study period or
within 5 months after the last dose.
9. For any condition requiring systemic treatment with corticosteroids (prednisone or
equivalent >10 mg/ day) or other immunosuppressive agents within 14 days
prior to the first administration of the study drug, the investigator assessed the
patient as having an impact on the study treatment.
10. Active autoimmune diseases requiring systemic treatment in patients assessed by the
investigator as having an impact on investigational treatment.
11. Patients with interstitial lung disease, non-infectious pneumonia, or other diseases
that are not under control, including diabetes, pulmonary fibrosis, acute lung
disease, etc., that the investigators have assessed as having an impact on the study
treatment.
12. Patients with a history of major diseases or clinical manifestations that may affect
the function of organ systems and are assessed by the investigator as having
implications for the study and treatment.
13. Study severe chronic or active infections (including tuberculosis) requiring
systemic antimicrobial, antifungal, or antiviral treatment ≤14 days before the first
administration of the drug.
14. Uncontrolled active hepatitis B (defined as positive HBV surface antigen [HBsAg]
test results during screening and HBV-DNA test values higher than the upper limit of
normal values in the laboratory of the research center; (Participants with HBV-DNA
levels < 500 IU/mL within 28 days prior to enrollment, who have received
local standard antiviral therapy for at least 14 days and who are willing to
continue antiviral therapy during the study period may be enrolled); Subjects with
active hepatitis C (defined as positive HCV surface antibody [HCsAb] test results
during screening, positive HCV-RNA);
15. Known human immunodeficiency virus (HIV) infection (known HIV antibody positive);
16. Grade III-IV congestive heart failure (New York Heart Association classification),
poorly controlled and clinically significant arrhythmias;
17. Any arterial thrombosis, embolism, or ischemia, such as myocardial infarction,
unstable angina pectoris, cerebrovascular accident, or transient ischemic attack,
occurred within 6 months prior to treatment;
18. Concurrent participation in another therapeutic clinical study, unless it is an
observational (non-interventional) clinical study or in the follow-up period of an
interventional study.
19. Medical history or evidence of disease that may interfere with the test results,
prevent participants from participating fully in the study, abnormal treatment or
laboratory test values, or other conditions that the investigator considers
unsuitable for enrollment. The Investigator considers that there are other potential
risks that are not suitable for participation in the study.
Gender:
All
Minimum age:
18 Years
Maximum age:
75 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Shandong Public Health Clinical Center (ShandongPHCC)
Address:
City:
JiNan
Zip:
250000
Country:
China
Status:
Recruiting
Contact:
Last name:
Hua Zhang, doctor
Phone:
0531-83347512
Email:
zhanghua_science@163.com
Start date:
August 27, 2024
Completion date:
September 10, 2027
Lead sponsor:
Agency:
Hua Zhang
Agency class:
Other
Source:
Shandong Public Health Clinical Center
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06617936
