Tirelizumab in Combination With Carboplatin and Albumin-binding Paclitaxel for Neoadjuvant Therapy in HNSCC

NCT05941338 | Recruiting Phase 2

• 1 other identifier: SYSKY-2023-159-01
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

In this study, 100 patients with resectable head and neck squamous cell carcinoma (oral squamous cell carcinoma and oropharyngeal squamous cell carcinoma) were enrolled, who were combined with tirelizumab, carboplatin and albumin-binding paclitaxel before and after surgery. Tumor tissues and paracancer tissues of patients were collected to observe the imaging and pathological changes before and after treatment. At the same time, clinical information of patients, such as pathological grade, stage, treatment, prognosis, serology, imaging, etc. were collected to evaluate the safety and feasibility of tirelizumab combined with carboplatin and albumin-binding paclitaxel for neoadjuvant therapy of resectable oral and oropharyngeal squamous cell carcinoma. This is a prospective, one-arm, phase II clinical study. Purpose Main purpose The efficacy of Tirelizumab combined with carboplatin and albumin-paclitaxel in neoadjuvant therapy for resectable head and neck squamous cell carcinoma was evaluated by calculating the major pathological response (MPR) rates in the experimental group. The severity of adverse events associated with neoadjuvant therapy will be graded according to NCI CTCAE (version 5.0) during the course of this study and during follow-up, the incidence of adverse events in the experimental and control groups will be compared, and the safety of neoadjuvant therapy with Tirelizumab combined with carboplatin and albumin-paclitaxel in resectable head and neck squamous cell carcinoma will be evaluated. Secondary Purpose

1. 1.One-year event survival rate and event-free survival (EFS) of enrolled patients were evaluated (five years);
2. 2.Pathological complete response rate (pCR) of enrolled patients was evaluated (5 years);
3. 3.pTR of enrolled patients was evaluated;
4. 4.Overall survival (OS) of enrolled patients was evaluated (5 years);
5. 5.Radiological response of enrolled patients was assessed;
6. 6.The rate of operation delay of enrolled patients was evaluated;

Conditions

Head and Neck Squamous Cell Carcinoma; Oral Cancer

Keywords

head and neck squamous cell carcinoma; oral cancer; pd-1

Outcome Measures

Primary Outcomes (2)

• Major pathologic response

  Pathologic response rate to neoadjuvant treatment in resected tumor and lymph nodes. The rate of major pathologic response, defined as \<10% residual viable tumor cells in the resection specimen will be compared to historic data with neoadjuvant chemotherapy.

  6 weeks

• Adverse events graded by CTCAE v5.0

  Percentage of adverse events that are possibly, probably or definitely related to study treatment per Criteria for Adverse Events version 5 (CTCAE v5.0).

  90 days after surgery

Secondary Outcomes (5)

• Pathologic complete response

  6 weeks

• Event-free survival (EFS)

  1 years and 5 years

• Overall survival（OS）

  5 years

• Operation delay rate

  2months

• Radiographic Response

  6 weeks

Other Outcomes (1)

• Exploratory purpose

  5 years

Study Arms (1)

Arm 1

EXPERIMENTAL

Drug:Tirelizumab , Carboplatin,albumin-bound paclitaxel Patients receive Tirelizumab IV on day 1, albumin-bound paclitaxel IV on day 1 and carboplatin IV on day 1 . Treatment repeats every 21 days for up to 2cycles in the absence of disease progression or unacceptable toxicity. Then surgery.

Drug: Tirelizumab ,+Carboplatin+albumin-bound paclitaxel

Interventions

Tirelizumab ,+Carboplatin+albumin-bound paclitaxel DRUG

Sintilimab (IV), dose= 200mg , day=1 , cycle length: 21 days. Carboplatin (IV), dose=300mg/m2, day= 1, cycle length: 21 days. albumin-bound paclitaxel (IV), dose=260mg/m2, day= 1, cycle length: 21 days. Intervention: Drug: Sintilimab , Carboplatin, albumin-bound paclitaxel

Arm 1

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• years of age ≤65 years of age;
• Cytological or histological diagnosis of surgically resectable squamous cell carcinoma of the head and neck with the following stages:
• T3-4a, N0-2, M0;
• According to the solid tumor efficacy evaluation criteria (RECIST version 1.1), there was at least one radiologically measurable lesion; First-line patients: have not previously received any systemic antitumor therapy for advanced/metastatic disease. Patients who had previously received platinum-containing adjuvant/neoadjuvant chemotherapy, or had received radical chemoradiotherapy for advanced disease, if the interval between disease progression or recurrence and the end of the last chemotherapy drug treatment was at least 6 months, were allowed to be enrolled in this study.
• ECOG score 0-1;
• Expected survival time \&gt; 3 months;
• Adequate organ function, subject shall meet the following laboratory indicators:
• The absolute value of neutrophil granulocyte (ANC) ≥1.5x109/L in the last 14 days without the use of granulocyte colony stimulating factor;
• Platelets ≥100×109/L without blood transfusion in the past 14 days;
• Hemoglobin \&gt without blood transfusion or use of erythropoietin within the last 14 days; 9g/dL;
• Total bilirubin ≤1.5× upper limit of normal value (ULN);
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5×ULN (ALT or AST ≤5×ULN in patients with liver metastasis);
• Serum creatinine ≤1.5×ULN and creatinine clearance (calculated by Cockcroft-Gault formula) ≥60 ml/min;
• Good coagulation function, defined as International Standardized ratio (INR) or prothrombin time (PT) ≤1.5 times ULN;
• Normal thyroid function, defined as thyroid stimulating hormone (TSH) within the normal range. Subjects whose baseline TSH is outside the normal range can be enrolled if total T3 (or FT3) and FT4 are within the normal range;

You may not qualify if:

• Malignant diseases other than head and neck squamous cell carcinoma diagnosed within 5 years prior to initial administration (excluding basal cell carcinoma of the skin after radical treatment, squamous epithelial carcinoma of the skin, and/or carcinoma in situ after radical excision);
• Currently participating in an interventional clinical study, or receiving other investigational drugs or using investigational devices within 4 weeks prior to initial dosing;
• Previous treatment with anti-PD-1, anti-PD-L1, or anti-PD-L2 drugs or drugs that target another stimulus or synergistic inhibition of T cell receptors (e.g., CTLA-4, OX-40, CD137);
• Systemic treatment with Chinese patent drugs or immunomodulatory drugs (including thymosin, interferon and interleukin, except for local use to control pleural effusion) with indications of anti-head and neck squamous cell carcinoma within 2 weeks before the first administration;
• An active autoimmune immune disease requiring systemic treatment (e.g. with disease-modifying drugs, glucocorticoids, or immunosuppressants) has occurred within 2 years prior to initial administration. Alternative therapies (such as thyroxine, insulin, or physiologic glucocorticoids for adrenal or pituitary insufficiency) are not considered systemic therapy;
• Was receiving systemic glucocorticoid therapy (excluding nasal, inhalation, or other routes of topical glucocorticoids) or any other form of immunosuppressive therapy within 7 days prior to initial administration; Note: Physiological doses of glucocorticoids (≤10 mg/ day of prednisone or equivalent) are permitted;
• Clinically uncontrollable pleural effusion/abdominal effusion (patients with no need to drain effusion or no significant increase of effusion after 3 days of stopping drainage could be included in the group);
• Known allogeneic organ transplantation (except corneal transplantation) or allogeneic hematopoietic stem cell transplantation;
• Those who are known to be allergic to the active ingredients or excipients of the drug in this study, Pabolizumab, carboplatin and albumin-binding paclitaxel;
• Has not fully recovered from toxicity and/or complications caused by any intervention before starting treatment (i.e., ≤ grade 1 or baseline, excluding weakness or hair loss);
• Known history of human immunodeficiency virus (HIV) infection (i.e. HIV 1/2 antibody positive);
• Untreated active hepatitis B (defined as HBsAg positive coupled with a detected HBV-DNA copy number greater than the upper limit of normal in the laboratory of the study center);
• Note: Hepatitis B subjects who meet the following criteria can also be enrolled:
• \) HBV viral load \&lt before initial administration; At 1000 copies /ml (200 IU/ml), subjects should receive anti-HBV therapy to avoid viral reactivation throughout the study treatment period 2) For subjects with anti-HBC (+), HBsAg (-), anti-HBS (-), and HBV viral load (-), prophylactic anti-HBV therapy is not required, but close monitoring of viral reactivation is required
• Active HCV infected subjects (HCV antibody positive and HCV-RNA level above the lower limit of detection);

Sponsors & Collaborators

• Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University: lead

Study Sites (1)

Sun yat-sun memorial hospital

Guangzhou, Guangdong, 510000, China

RECRUITING

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck; Mouth Neoplasms; Parkinson Disease 4, Autosomal Dominant Lewy Body

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Head and Neck Neoplasms; Neoplasms by Site; Mouth Diseases; Stomatognathic Diseases

Central Study Contacts

Haotian Cao, MD

CONTACT

+8618583879908; caobleat@hotmail.com

Jinsong Li

CONTACT

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 5, 2023
• First Posted: July 12, 2023
• Study Start: March 1, 2023
• Primary Completion: February 28, 2025
• Study Completion (Estimated): February 28, 2030
• Last Updated: July 12, 2023

Record last verified: 2023-03

Locations

CN (1)