Toripalimab Combined With Chemotherapy in Primary Tracheal Squamous Cell Carcinoma

Study Overview
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Brief Summary
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This is a single-arm, open, II phase study to evaluate the safety and efficacy of Toripalimab + carboplatin + paclitaxel in 15 newly diagnosed patients with tracheal malignant tumors.

Official Title
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Clinical Study of Neoadjuvant Anti-PD-1 Drug Toripalimab Combined With Chemotherapy in the Treatment of Primary Tracheal Squamous Cell Carcinoma

Conditions
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Tracheal Squamous Cell Carcinoma

Intervention / Treatment
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* Drug: Toripalimab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Bronchoscopic biopsy confirmed as tracheal malignant tumor by pathological examination PET-CT confirmed no metastasis; ECOG physical status score 0-1; Bronchoscopy, chest CT is evaluated as early or locally advanced tracheal malignant tumor, and radical surgery is expected to be feasible or after neoadjuvant therapy. Age ≥ 18 years; Have one measurable lesions at least; Good function of other major organs (liver, kidney, blood system, etc.):-absolute neutrophil count ((ANC) ≥ 1.5 × 109), platelet (≥ 100 × 109), hemoglobin (≥ 90g/L). Note: patients shall not receive blood transfusion or growth factor support within 14 days before blood collection during the screening period;-International standardized ratio (INR) or prothrombin time (PT) ≤ 1.5 × normal upper limit (ULN);-activated partial thromboplastin time (APTT) ≤ 1.5 × ULN;- serum total bilirubin ≤ 1.5 × ULN (Gilbert syndrome patients with total bilirubin must be < 3×ULN). Fertile female patients with aspartate and alanine aminotransferase (AST and ALT) ≤ 2.5 × ULN, or liver metastasis with AST and ALT ≤ 5 × ULN Fertile female patients must voluntarily take effective contraceptive measures more than 120 days after chemotherapy or the last administration of triplizumab, whichever is later, and the urine or serum pregnancy test results less than 7 days before entering the group were negative. Unsterilized male patients must voluntarily take effective contraceptive measures ≥ 120 days after chemotherapy or the last administration of triplizumab, whichever is the later. Sign informed consent; Exclusion Criteria: Systemic anticancer therapy for tracheal malignant tumors, including surgery, radiotherapy, chemotherapy, targeted therapy and experimental therapy. Any Chinese herbal medicine used to control cancer was used within 14 days before the first administration of the study drug; Patients with other malignant tumors in the five years before the start of this trial. Complicated with unstable systemic diseases, including active infections, uncontrolled hypertension, unstable angina pectoris, congestive heart failure [higher than II (New York College of Cardiology)], severe arrhythmias, liver, kidney or metabolic diseases; Active, known or suspected autoimmune diseases, or autoimmune paraneoplastic syndrome requiring systemic treatment; The infection was treated with antibiotics within 4 weeks before the start of the trial; A history of active bleeding or embolism within 6 months, or received thrombolysis or anticoagulation therapy, or the researchers believe that there is an obvious tendency of gastrointestinal bleeding (such as esophageal varices have the risk of bleeding, local active ulcer lesions, etc.); Had or is suffering from nephrotic syndrome Has been or is suffering from chronic obstructive pneumonia, bronchiectasis, or interstitial lung disease; Allergic to experimental drugs; Complicated with HIV infection or active hepatitis. Vaccination within 4 weeks before the start of this trial; Those who had undergone other major operations or severe injuries within the previous 2 months; Clinically uncontrolled pleural effusion or ascites requiring pleural or abdominal puncture drainage within 2 weeks before admission; Pregnant or lactating women; Those with neurological diseases or mental disorders. Participated in another therapeutic clinical study at the same time; Other researchers did not consider it appropriate to enroll in the group.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Toripalimab<br> | Drug: Toripalimab<br>* Neoadjuvant treatment stage: Toripalimab 240mg, Carboplatin AUC5+ paclitaxel 200 mg/m ², iv, 3 weeks per cycle, 2-4 cycles in total; Surgical treatment stage: Patients with tracheal malignant tumor received radical surgery after neoadjuvant therapy, and patients who could not or refused surgical treatment due to various reasons were treated with multidisciplinary discussion. Adjuvant treatment stage: Toripalimab 240mg, Carboplatin AUC5+ paclitaxel 200 mg/m ²,iv, up to 4 cycles (including neoadjuvant stage).<br>* Other names: paclitaxel;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety: frequency of severe adverse events | The frequency of severe adverse events from the participants enrolling to 30 days after the last drug administration or 30 days after surgery or new anti-cancer therapy, which comes first. | up to 5 months | 
| Major pathologic response (MPR) | MPR is defined as the proportion of participants who have achieved major pathologic response (on routine hematoxylin and eosin staining, tumors with no more than 10% viable tumor cells) in all participants who have completed the neoadjuvant therapy before surgery. | up to 4 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival (OS) | It is defined as the time from enrollment to death of participant due to any cause. In the case of a patient who still survives at the time of analysis, the date of last contact will be taken as the censoring date. In the event of a patient with the survival status unknown, the date when the patient is last known to be alive will be used for interpolation (censoring). | up to 60 months | 
| Progression-free survival (PFS) | PFS is defined as the time from the enrollment of the subject to the first determination of disease progression or death of any cause according to RECISTv1.1, whichever occurs first. | up to 60 months | 
| Duration of remission (DOR) | According to the time from the first recording of objective remission to relapse or death from any cause determined by RECISTv1.1, whichever occurs first. | up to 60 months | 
| Disease control rate (DCR) | The proportion of patients whose best overall remission (BOR) is CR, PR or disease stable (SD) according to RECISTv1.1 evaluation | up to 60 months | 
| Health related quality of life (HRQol) | The assessment is made according to the Quality of Life Scale for Lung Cancer Patients (EORTC-QLQ-C30 & LC13, Version 3). EORTC's QLQ-C30 & LC13 (V3.0) is a core scale for lung cancer patients, with a total of 43 items. Among them, Item 29 and 30 are divided into seven grades, which are assigned with 1 to 7 scores according to the answer options. The other items are divided into 4 grades | up to 6 months |