Immunotherapy, Nasopharyngeal Carcinoma, Phase II Clinical Study, TPF
Conditions
Keywords
TPF, Immunotherapy, Nasopharyngeal Carcinoma, phase II clinical study
Brief summary
NPC is one of the most common malignant tumors in the head and neck region of China. Currently, the main treatment regimen for LA-NPC is radical concurrent chemoradiotherapy combined with induction or adjuvant chemotherapy. However, after radical radiotherapy and chemotherapy treatment, 15% -30% of patients still experience recurrence or distant metastasis. At present, the treatment options for R/M-NPC are very limited, especially for patients with recurrent or metastatic nasopharyngeal carcinoma who have failed second-line treatment, there is no standard treatment plan. Therefore, it is urgent to study a new treatment mode to improve the therapeutic efficacy of LA-NPC, thereby reducing the recurrence and metastasis rates. This study explores the safety and efficacy of TPF combined with immune checkpoint inhibitor induction therapy in LA-NPC patients through prospective research. The results of this study are expected to provide new ideas and methods for the treatment of LA-NPC and provide reference for clinical practice. The investigators believe that induction chemotherapy combined with immunotherapy has broad application prospects in the field of LA-NPC, and is expected to bring better treatment effects and quality of life to patients, bringing new hope to the medical community and patients. According to the inclusion criteria, eligible patients will be included: Induction chemotherapy with Tislelizumab combined with TPF regimen, administered every 3 weeks: albumin paclitaxel (200mg/m2), cisplatin (60mg/m2, infused over 3 days), 5-fluorouracil (3000mg/m2, continuously intravenously pumped for 120 hours), and PD-1 inhibitor (Tislelizumab 200mg). All patients received 3 cycles of induction therapy followed by radical concurrent chemoradiotherapy combined with Tislelizumab (200mg) treatment, Q3W. The cisplatin in the synchronous chemoradiotherapy regimen is administered once a week, with a dose of 40mg/m2 per dose, and the total dose of cisplatin does not exceed 100mg/m2. For patients who cannot tolerate cisplatin during synchronous radiotherapy and chemotherapy, cisplatin may not be combined. The IMRT radiotherapy area includes the primary tumor volume (GTVp), the total tumor volume of the affected lymph nodes (GTVn), the high-risk clinical target volume (CTV1), and the low-risk clinical target volume (CTV2). PTVp, PTV1, and PTV2 are respectively expanded by 3mm on GTVp, CTV1, and CTV2. The prescription doses for PTVp, PTVn, PTV1, and PTV2 are 70-72 Gy, 66-70 Gy, 60-68 Gy, and 54-58 Gy, respectively, with a total of 30-33 divided exposures. After the completion of synchronous radiotherapy and chemotherapy, adjuvant therapy with Tislelizumab (Tislelizumab 200mg d1, once every 3 weeks, for a total of 8 courses) is administered. For patients with high-risk recurrence factors (T4 or N2), combination chemotherapy with capecitabine 625mg/m2 po bid is performed for one year. Treat until any of the following conditions occur: Disease progression; No clinical benefit; Intolerable toxicity; Withdrawal of informed consent; Or maintain treatment for up to six months.
Interventions
DRUGalbumin paclitaxel (200mg/m2), cisplatin (60mg/m2, infused over 3 days), 5-fluorouracil (3000mg/m2, continuously intravenously pumped for 120 hours), and tislelizumab ( 200mg).
Induction chemotherapy with PD-1 inhibitor combined with TPF regimen, administered every 3 weeks: albumin paclitaxel (200mg/m2), cisplatin (60mg/m2, infused over 3 days), 5-fluorouracil (3000mg/m2, continuously intravenously pumped for 120 hours), and PD-1 inhibitor ( 200mg). All patients received 3 cycles of induction therapy followed by radical concurrent chemoradiotherapy combined with tislelizumab (200mg) treatment, Q3W. The cisplatin in the synchronous chemoradiotherapy regimen is administered once a week, with a dose of 40mg/m2 per dose, and the total dose of cisplatin does not exceed 100mg/m2. For patients who cannot tolerate cisplatin during synchronous radiotherapy and chemotherapy, cisplatin may not be combined.
Sponsors
Weiwei Zhang
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
TPF induction chemotherapy combined with tislelizumab+cisplatin concurrent chemoradiotherapy combined with tislelizumab adjuvant therapy (experimental group): TPF induction chemotherapy (albumin paclitaxel 200mg/m2+cisplatin 60mg/m2, divided into 3 days of infusion+5-fluorouracil 3000mg/m2, continuously intravenously pumped for 120 hours)+trastuzumab 200mg d1, once every 3 weeks, for a total of 3 courses+concurrent chemoradiotherapy combined with tislelizumab (cisplatin 100mg/m2+tislelizumab 200mg, starting from the first day of radiotherapy, once every 3 weeks during radiotherapy, for a total of 3 courses), synchronous IMRT+tislelizumab adjuvant therapy (tislelizumabb 200mg d1, once every 3 weeks) (8 trips in total)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Age ≥ 18 years old, ≤ 75 years old, gender not limited; 2. Pathological diagnosis of nasopharyngeal non keratinizing carcinoma (differentiated or undifferentiated, i.e. WHO classification II or III); 3. Stage III-IVa (8th AJCC/UICC stage), excluding T3N0-1M0 patients; 4. Newly diagnosed nasopharyngeal carcinoma patients who have not received any anti-tumor treatment in the past; 5. The physical fitness score of the Eastern Cooperative Oncology Group (ECOG) in the United States ranges from 0 to 1; 6. Having sufficient organ and bone marrow function, defined as follows: 1. Blood routine: Neutrophil count (NEUT #) ≥ 1.5 × 109/L; Platelet count (PLT) ≥ 80 × 109/L; Hemoglobin ≥ 8 g/dL; 2. Liver function: Aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) ≤ 2.5 x upper limit of normal (ULN); Total bilirubin (TBIL) ≤ 1.5 × ULN; 3. Albumin ≥ 2.8 g/dL; 4. Renal function: serum creatinine (Cr) ≤ 1.5 × ULN or creatinine clearance rate (CCR)\>60 ml/min; 5. Coagulation function: International Normalized Ratio (INR) ≤ 1.5; Partial thromboplastin time (APTT) ≤ 1.5 × ULN; 7. The subjects voluntarily joined this study, signed an informed consent form, and were able to comply with the visit and related procedures specified in the protocol.
Exclusion criteria
1. Medical history of other malignancies (except for cured skin basal cell carcinoma, skin squamous cell carcinoma, superficial bladder cancer, cervical carcinoma in situ, gastrointestinal intramucosal carcinoma and other malignancies that the researchers think can be included); 2. Any active autoimmune disease or autoimmune disease history, including but not limited to immune related neurological disease, multiple sclerosis, autoimmune (demyelinating) neuropathy, Guillain Barre syndrome, myasthenia gravis, systemic lupus erythematosus (SLE), connective tissue disease, scleroderma, inflammatory bowel disease, including Crohn's disease and ulcerative colitis, autoimmune hepatitis, toxic epidermal necrolysis (TEN) or Stevens Johnson syndrome (except for type I diabetes mellitus using a stable dose of insulin); 3. Individuals with allergic diseases, a history of severe drug allergies, and known allergies to any component of macromolecular protein preparations or PD-1 monoclonal antibody injections (note: severe allergies may result in hospitalization); 4. Received any of the following treatments: 1. Patients who have previously used PD-1 antibody, PD-L1 antibody, PD-L2 antibody, CTLA-4 antibody; 2. Individuals who have received anti-tumor vaccines; 3. Use any active vaccine against infectious diseases (such as influenza vaccine, chickenpox vaccine, etc.) within 4 weeks before the first administration or during the planned study period; 4. Having undergone major surgery or suffered serious trauma within 4 weeks prior to the first administration of medication; 5. The toxicity of previous anti-tumor treatments has not recovered to ≤ CTCAE 5.0 Grade 1 (excluding hair loss and sequelae related to previous platinum therapy neurotoxicity) or the level specified in the inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| objective response rate | From enrollment to the end of 3 cycles (each cycle is 21 days) introduction therapy | Proportion of patients with complete remission (CR) and partial remission (PR) |
Countries
China
Contacts
Primary ContactWeiwei Zhang, PhD
Outcome results
None listed