Adaptive Radiotherapy, NSCLC, Sintilimab
Conditions
Keywords
V20, stage III NSCLC, Adaptive Radiotherapy, sintilimab
Brief summary
To evaluate the Efficacy and Safety of the Combination of Sintilimab With Platinum-doublet Chemotherapy and Adaptive Radiotherapy Strategy in the Treatment of Stage III Non-small Cell Lung Cancer Patients
Interventions
DRUGExperimental
Drug: Sintilimab, 200mg IV D1 Q3W, Cisplatin, 75mg/m2 D1 IV Q3W or Carboplatin AUC 5 D1 IV Q3W, Paclitaxel or Paclitaxel liposome 135-175mg/m2 D1 IV Q3W(Squamous） Drug: Sintilimab, 200mg IV D1 Q3W, Cisplatin, 75mg/m2 D1 IV Q3W or Carboplatin AUC 5 D1 IV Q3W, Pemetrexed, 500mg/m2 D1 IV Q3W(adenocarcinoma） Radiation:Adaptive radiotherapy with V20\<20%: 1.PGTV60-66Gy/2.0-2.2Gy/30F;PTV54Gy/1.8Gy/30F;2.PGTV54-66Gy/2.0-2.2Gy/30F；3.PGTV50Gy/2.0Gy/25F
Sponsors
The Third Xiangya Hospital of Central South University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. The subjects are willing and able to comply with the scheduled visits, treatment plans, laboratory tests, and other requirements of the study 2. Age range of 18-75 years old upon enrollment, both male and female are eligible 3. Stage III NSCLC confirmed by histology or cytology (according to the International Union Against Cancer and the Joint American Committee on Cancer 8th edition TNM staging of lung cancer) 4. It was clarified that surgical resection is not possible After MDT discussion, 5. The main driver genes have no sensitive mutations (including EGFR, ALK, ROS1, MET, HER2, etc.) 6. No previous systematic anti-tumor treatment or chest radiotherapy for NSCLC 7. According to RECIST v1.1, there is at least one measurable lesion, and according to RECIST v1.1, this lesion is suitable for repeated and accurate measurements 8. There is sufficient organ function reserve to meet the needs of clinical research
Exclusion criteria
1. There are any small cell carcinoma components present in the histopathology, as well as special types such as salivary gland type and SMARCA4 deficiency 2. Except for NSCLC, the subjects had other malignant tumors within the 5 years prior to enrollment. Subjects with other tumors that have been cured by local treatment, such as basal or cutaneous squamous cell carcinoma, superficial bladder cancer, cervical or breast cancer in situ, are not excluded 3. Previously received local treatments for tumor lesions such as thoracic radiotherapy and radiofrequency ablation 4. Received non-specific immunomodulatory therapy (such as interleukin, interferon, thymosin, tumor necrosis factor, etc., excluding IL-11 used to treat thrombocytopenia) within 2 weeks before the first administration; Received Chinese herbal medicine or traditional Chinese patent medicines and simple preparations with anti-tumor indications within 1 week before the first administration 5. Suffering from active autoimmune diseases that require systematic treatment within the past two years 6. History of immunodeficiency; Individuals who test positive for HIV antibodies; Currently in long-term use of systemic corticosteroids or other immunosuppressants 7. Subjects who are known to have active pulmonary tuberculosis (TB) and suspected of having TB need to undergo clinical examination to exclude them; Known active syphilis infection 8. Known history of allogeneic organ transplantation and allogeneic hematopoietic stem cell transplantation 9. Previous or current non infectious pneumonia/interstitial lung disease requiring systemic corticosteroid therapy 10. Serious infection occurred within 4 weeks prior to the first administration, including but not limited to comorbidities requiring hospitalization, sepsis, or severe pneumonia; Active infections that have received systemic anti infective therapy within 2 weeks prior to the first administration (excluding antiviral therapy for hepatitis B or C) 11. Current active hepatitis B subjects (HBsAg positive and HBV-DNA exceeding 1000 copies/ml (200IU/ml) or above the detection limit) 12. Tumor invasion or compression of important surrounding organs (such as aorta, heart and pericardium, superior vena cava, trachea, esophagus, etc.) or the risk of developing esophagotracheal fistula or esophageal pleural fistula; Tumor mediastinal lymph node metastasis invading the trachea and main bronchus with the risk of bronchial fistula 13. History of myocarditis, cardiomyopathy, and malignant arrhythmia in the past 14. Within 6 months prior to the first administration, there is a history of esophageal and gastric varices, severe ulcers, unhealed wounds, gastrointestinal perforation, abdominal fistula, gastrointestinal obstruction, intra-abdominal abscess, or acute gastrointestinal bleeding 15. Any arterial thromboembolic event, NCI CTCAE 5.0 grade 3 or higher venous thromboembolic event, transient ischemic attack, cerebrovascular accident, hypertensive crisis, or hypertensive encephalopathy occurred within 6 months prior to the first administration; Currently, there is hypertension and after treatment with oral antihypertensive drugs, the systolic blood pressure is ≥ 160mmHg or the diastolic blood pressure is ≥ 100mmHg 16. History of severe bleeding tendency or coagulation dysfunction 17. Received a live vaccine within 30 days prior to the first administration, or planned to receive a live vaccine during the study period 18. Known to be allergic to any component of any anti-tumor drug; Known history of severe hypersensitivity reactions to other monoclonal antibodies 19. Known history of mental illness, drug abuse, alcoholism, or drug use 20. Pregnant or lactating women 21. Any past or current diseases, treatments, or laboratory abnormalities that may confuse the research results, affect the participants' full participation in the study, or may not be in the best interests of the participants 22. Local or systemic diseases caused by non malignant tumors, or diseases or symptoms secondary to tumors, which can lead to higher medical risks and/or uncertainty in survival evaluation, such as tumor like leukemia reactions (white blood cell count\>20 × 109/L), cachexia manifestations (such as known weight loss of more than 10% in the first 3 months of screening), etc
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free Survival (PFS) | 28 months | The time from the beginning of treatment to the time when the disease progresses or the patient dies from any cause |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) | 28 months | the rate of patients with PR and CR |
| Disease Control Rate (DCR) | 28 months | the rate of patients with PR and CR and SD |
| Overall Survival (OS) | 28 months | The time from the beginning of treatment to the time when the patient dies from any cause |
| Duration of response (DoR) | 28 months | Duration of Response (DoR) is defined as the time from the date of first documented objective response (Complete Response \[CR\] or Partial Response \[PR\]) to the date of first documented disease progression or death from any cause, whichever occurs first. Patients who have not experienced disease progression or death at the time of analysis will be censored at the date of their last adequate tumor assessment. |
| In-field local control rate | 28 months | In-field local control rate is defined as the proportion of participants without disease progression within the irradiated field, assessed according to RECIST version 1.1. In-field progression is defined as a ≥20% increase in the longest diameter of the target lesion relative to the smallest sum of diameters recorded since treatment initiation, or the appearance of a new malignant lesion within the radiation field or at its margin. The time to in-field local failure is measured from the start of radiotherapy to the date of documented in-field progression, death without in-field progression (censored), or last known follow-up (censored). |
| Out-of-field recurrence rate | 28 month | Out-of-field recurrence rate is defined as the proportion of participants who develop disease recurrence or progression outside the Planning Target Volume (PTV). Out-of-field recurrence is defined as the appearance of a new lesion or progression (≥20% increase in the longest diameter relative to the smallest sum of diameters recorded since treatment initiation per RECIST version 1.1) at a site completely outside the PTV. The time to out-of-field recurrence is measured from the start of radiotherapy to the date of documented out-of-field recurrence, death without out-of-field recurrence (censored), or last known follow-up (censored). |
| AE | 28 months | Incidence of Treatment-Emergent Adverse Events |
Countries
China
Contacts
CONTACTXueWen Liu
Outcome results
None listed