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The goal of this type of study: single center exploratory clinical trial is to evaluate the efficacy and safety of Toripalimab combined with AP-induced chemotherapy followed by concurrent chemoradiotherapy and Toripalimab-maintenance therapy sequentially in patients with non-metastatic IVB hypopharyngeal cancer. The main question[s] it aims to answer are: • [main objectives: to evaluate the objective remission rate (ORR), progression-free survival (PFS) and safety of PD-1 inhibitor Toripalimab combined with induction chemotherapy (cisplatin / nedaplatin + albumin paclitaxel) in patients with locally advanced head and neck squamous cell carcinoma according to RECISTv1.1.] • [Secondary objectives: 1-year, 2-year, 3-year progression-free survival rate (PFS); 1-year, 2-year, 3-year overall survival rate (OS); overall survival time (OS); tumor regression time; quality of life was evaluated by ECOG physical status and EQ-5D-5L assessment. ] [Exploratory Objective: to explore the relationship between the biomarkers in tumor tissue and / or blood, including PD-L1 (CPS/TPS), HPV (P16), PD-1, TMB, EGFR, CD3, CD4, CD8, TP53, MSI-H and the efficacy of immunotherapy, and the relationship between MDM2/MDM4, EGFR, chromosome 11q13 interval (CCND1/FGF19/FGF3/FGF4) and immune hyperprogression] Participants will [be treated with Toripalimab injection (240mg/, once every 3 weeks) combined with cisplatin / nedaplatin (40mg) and albumin paclitaxel (230mg/m2, once every 3 weeks). The efficacy was evaluated within 1 week after induction therapy. In the phase of simultaneous radiotherapy, albumin paclitaxel (230mg/m2, once every 3 weeks, D1/D21/D43) was used. One month after the end of synchronous radiotherapy and chemotherapy, the efficacy was evaluated. After evaluation, all patients entered the next stage of immune maintenance therapy. During the maintenance phase, Toripalimabv injection (240mg/, once every 3 weeks) was given for 6 months or until the disease progressed, the toxicity was intolerable, the subjects asked to withdraw voluntarily, and the researchers judged that the subjects needed to withdraw from the study. The patients were treated with spiral tomographic radiotherapy (TOMO) or intensity modulated radiotherapy (IMRT).. These patients were given Nimotuzumab injection at the same time during simultaneous radiotherapy and chemotherapy.](streamdown:incomplete-link)
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Toripalimab +AP-induced chemotherapy | Experimental | Study drug: toripalimab JS001 dosage:240mg Drug administration plan and mode:Intravenous infusion of 30min (not less than 20min and not more than 60min), followed by observation of 60min (only the first 2 cycles), once every 3 weeks (Q3W). |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Cisplatin/Nedaplatin, albumin paclitaxel | Drug | During induction chemotherapy, triplelimab JS001 was administered before cisplatin/Nedaplatin and albumin paclitaxel. JS001 Intravenous infusion of cisplatin/Nedaplatin was administered 60 minutes after the end of infusion and beginning on day 1 of each cycle 40mg/m 2, D1, D2 albumin paclitaxel 230 mg/m 2; Chemotherapeutic drugs are administered in accordance with the drug label and local prodrome and other standard protocols for prophylactic use, every 3 Once a week (Q3W) for 2 cycles |
| Measure | Description | Time Frame |
|---|---|---|
| Objective Response Rate (ORR) | An objective response is defined as either a confirmed CR or a PR, as determined by the investigator using RECIST v1.1Response Evaluation Criteria in Solid Tumors (RECIST) from the National Cancer Institute (NCI). | 3 years |
| Progress-free survival (PFS) | Defined from date of randomization to date of first documentation of progression or death due to any cause For example, increased tumor burden (including new small lesions in non critical areas), physical fitness status, and experimentation If there is no significant deterioration in the room value, treatment is allowed to continue until at least 4 weeks later or the next planned period Repetitive imaging examination confirms disease progression at the time point of imaging examination | 1years, 2 years , 3 years |
| Incidence rate of adverse events (AEs) | Analysis of adverse events (AEs) are based on treatment-related AEs (trAEs) and immune-related AEs (irAEs), and all-grade AEs and grade 3-4 AEs. AEs are evaluated by investigators according to the Common Terminology Criteria for Adverse Events, version 5.0 | 3 years |
| Measure | Description | Time Frame |
|---|---|---|
| Overall survival (OS) | Defined from date of randomization to date of first documentation of death from any cause or censored at the date of the last follow-up. | 1years, 2 years , 3 years |
| ECOG physical fitness status |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Xinxin Zhang | Contact | 15910520109 | xinxinzhang66@hotmail.com |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| 中国人民解放军总医院 | Recruiting | Beijing | China |
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| ID | Term |
|---|---|
| D007012 | Hypopharyngeal Neoplasms |
| ID | Term |
|---|---|
| D010610 | Pharyngeal Neoplasms |
| D010039 | Otorhinolaryngologic Neoplasms |
| D006258 | Head and Neck Neoplasms |
| D009371 | Neoplasms by Site |
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| ID | Term |
|---|---|
| D002945 | Cisplatin |
| C053989 | nedaplatin |
| ID | Term |
|---|---|
| D017606 | Chlorine Compounds |
| D007287 | Inorganic Chemicals |
| D017672 | Nitrogen Compounds |
| D017671 | Platinum Compounds |
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The physical condition of patients in the evaluation group was evaluated by ECOG score
| Once a week for the duration of treatment, 15, 18, 21, and 24 months after completion of treatment |
| Tumor regression time | 3 years |
| Quality of Life (QOL) | Evaluate the quality of life of patients in the evaluation group through EQ-5D-5L assessment | 3 years |
| D009369 | Neoplasms |
| D010608 | Pharyngeal Diseases |
| D009057 | Stomatognathic Diseases |
| D010038 | Otorhinolaryngologic Diseases |