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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Participant Group/Arm A | Experimental | Participants receive 2-4 cycles of Tislelizumab With Recombinant human endostatin combined with Chemotherapy treatment during preoperative period, every 3 weeks once for 4 cycles at most. After neoadjuvant therapy, Patients evaluated for MDT who can be surgically resected will be placed in the surgical group for surgical excision. Surgery will be performed within 4 to 6 weeks after completion of preoperative therapy. After surgery, participants will receive adjuvant therapy with tislelizumab combined with recombinant human endostatin injection every 3 weeks until disease progression or postoperative adjuvant therapy for 1 year. |
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| Participant Group/Arm B | Experimental | Participants receive 2-4 cycles of Tislelizumab With Recombinant human endostatin combined with Chemotherapy treatment , every 3 weeks once for 4 cycles at most. After neoadjuvant therapy, Patients evaluated by MDT as unresectable will be placed in the standard treatment group, where the investigator will select the standard treatment regimen determined by the MDT discussion. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| neoadjuvant therapy:Tislelizumab With Recombinant human endostatin combined with Chemotherapy | Drug | 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) |
| Measure | Description | Time Frame |
|---|---|---|
| Surgical resection rate | Proportion of patients who underwent surgical resection after induction therapy | From enrollment to the end of surgery |
| Measure | Description | Time Frame |
|---|---|---|
| Objective response rate (ORR) | ORR is defined as the percentage of participants having a complete response or a partial response, measured by RECIST 1.1. | prior to surgery |
| Event-Free Survival(EFS) |
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Have fully understood the study and voluntarily signed the informed consent;
Age 18-75 years old, gender is not limited;
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.
At least 1 measurable lesion as defined by RECIST v1.1;
ECOG score 0-1;
Eligible for platinum-containing double-drug chemotherapy.
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
Willing and able to comply with study plan visits, treatment plans, laboratory tests and other study procedures;
The total amount of lung function, as assessed by the surgeon, is sufficient to withstand the proposed pneumonectomy;
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:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Hua Zhang, PhD | Contact | 0531-83347512 | zhanghua_science@163.com |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Shandong Public Health Clinical Center (ShandongPHCC) | Recruiting | Jinan | Shandong | 250000 | China |
Protect patient privacy
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| surgery | Procedure | 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. |
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| Adjuvant therapy:Tislelizumab and Recombinant Human Endostatin Injection (Endostar) | Drug | 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. |
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| Standard Treatment | Other | 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 |
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The time from the start of randomization (or the start of treatment in a one-arm trial) to the first occurrence of any of the following events: disease progression without surgical treatment, local or distant recurrence, death from any cause, etc.
| Up to 2years |
| Pathological Complete Response (pCR) Rate | no residual tumor cells in the surgically resected tumor specimen and all sampled regional lymph nodes after neoadjuvant treatment. | 1 month after surgery |
| Major Pathological Response (MPR) Rate | Major Pathological Response (MPR) Rate: defined as ≤ 10% of residual tumor cells in the surgically resected tumor specimen and sampled regional lymph nodes after neoadjuvant treatment. | 1 month after surgery |
| Progression-Free Survival (PFS) | Progression-Free Survival (PFS): defined as the time from the first dose until the date of first documented progression or date of death from any cause, whichever came first. | Up to 12 months |
| Overall Survival | Time from randomization to death (from any cause) | 3 years |
| 1 years event free survival (EFS) | 1 years EFS rate is defined as the percentage of participants having no radiographic disease progression, local progression precluding surgery, inability to resect the tumor, local or distant recurrence, or death due to any cause within 1years after randomization. | 1 years |
| 1 years Progression-Free Survival (PFS) | 1 years Progression-Free Survival (PFS): defined as the time from the first dose until the date of first documented progression or date of death from any cause, whichever came first within 1 years after randomization. | 1 years after randomization |
| 1 years overall survival rate (OS) | 1 years OS rate is defined as the percentage of participants having no death of any cause within 1 years after operation.The Kaplan-Meier estimator will be used to estimate median OS and its 95%CI and the survival curve. | 1 years after randomization |
| R0 Resection Rate | R0 Resection Rate: The pathological results will showed that the incision margin was negative and no residual cancer cells were found under the microscope. | 1 month after surgery |
| Safety and Tolerability | Number of participants with treatment-related adverse events as assessed by CTCAE v5.0 | Up to 3 years |
| ID | Term |
|---|---|
| D004358 | Drug Therapy |
| D013514 | Surgical Procedures, Operative |
| D043169 | Endostatins |
| C522911 | endostar protein |
| ID | Term |
|---|---|
| D013812 | Therapeutics |
| D043165 | Angiostatic Proteins |
| D042501 | Angiogenic Proteins |
| D036341 | Intercellular Signaling Peptides and Proteins |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
| D011506 | Proteins |
| D043170 | Collagen Type XVIII |
| D024041 | Non-Fibrillar Collagens |
| D003094 | Collagen |
| D016326 | Extracellular Matrix Proteins |
| D012596 | Scleroproteins |
| D001685 | Biological Factors |
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