4 Courses vs 2 Courses of Pembrolizumab Combined With Carboplatin and Albumin-binding Paclitaxel of Neoadjuvant Therapy in HNSCC

NCT05980702 | Recruiting Phase 2

• 1 other identifier: SYSKY-2023-219-02
• Study Type: interventional
• Target: 192
• Locations: 1 country
• Sites: 1

Brief Summary

In this study, 200 patients with resectable head and neck squamous cell carcinoma (T3 or T4, N0) were enrolled and preoperatively combined with pembrolizumab (PD-1 inhibitor), carboplatin, and albumin-binding paclitaxel. The subjects were randomly divided 1:1 into four treatments and two treatments. The imaging and pathological changes of tumor and paracancer tissues before and after treatment were observed. Clinical information, such as pathological grade, stage, treatment, prognosis, serology, imaging, etc., was collected to evaluate the safety and efficacy of 4-course pembrolizumab combined with carboplatin and albumin-binding paclitaxel compared with 2-course neoadjuvant therapy for resectable oral and oropharyngeal squamous cell carcinoma. This is a prospective, one-arm, phase II clinical study. Main purpose By calculating pathological complete response (pCR) in the experimental group, we evaluated the efficacy (optimality) of four courses of pembrolizumab combined with carboplatin and albumin-binding paclitaxel compared with two courses of neoadjuvant therapy for resectable oral and oropharyngeal squamous cell carcinoma (T3 or T4, N0). At the same time, this study evaluated the safety of medication, specifically: The severity of adverse events associated with neoadjuvant therapy will be graded according to NCI CTCAE (version 5.0) during this study and during follow-up, and the occurrence of adverse events in the experimental and control groups will be compared. To evaluate the safety of 4-course Pembrolizumab combined with carboplatin and albumin-binding paclitaxel compared with 2-course neoadjuvant therapy for resectable oral and oropharyngeal squamous cell carcinoma (T3 or T4, N0). Secondary Purpose

1. 1.The event-free survival (EFS) of the two groups were compared;
2. 2.The main pathological response rate (MPR) of the two groups were compared;
3. 3.pTR of the two groups was compared;
4. 4.Overall survival (OS) of the two groups was compared;
5. 5.The radiological responses of the two groups were compared;
6. 6.The operation delay rate of the two groups was compared; Exploratory purpose For the response of enrolled patients after treatment, group treatment was conducted according to the guidelines, and stratified factors influencing the prognosis and treatment plan of immunotherapy were explored according to stratification. The stratification factors taken into consideration are: P16 status, smoking history, TNM stage, tumor reduction (MPR condition), presence of risk factors (according to the guidelines, risk factors are presence of episopercular invasion, positive incisal margin, proximal incisal margin, pT3 or pT4, pN2 or pN3 lymph nodes located in the IV and V regions of the neck, Nerve invasion, vascular invasion, etc.). The purpose of this study was to stratified risk factors for evaluating the efficacy of pembrolizumab combined with carboplatin and albumin-paclitaxel in neoadjuvant therapy for resectable head and neck squamous cell carcinoma. At the same time, hematological, pathological and fecal indicators collected in the design of the experiment were collected. Correlation analysis was conducted to statistically analyze the relationship between these indicators and the therapeutic effect of the program.

Conditions

HNSCC; Oral Cancer; PD-1

Keywords

HNSCC; Oral Cancer; PD-1

Outcome Measures

Primary Outcomes (2)

• Percentage of 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). Change From Baseline 90 days after surgery.

  Time Frame: 90 days after surgery

• percentage of pathologic complete response(pCR)

  The absence rate(Percentage) of invasive/in situ cancer and/or axillary lymph nodes.Change From Baseline from 6 weeks.

  6 weeks

Secondary Outcomes (4)

• Event-free survival (EFS)

  5 years

• Overall survival(OS)

  5 years

• Operation delay rate

  2 months

• Radiographic Response

  6 weeks

Study Arms (2)

4 courses arm

EXPERIMENTAL

Drug:Pembrolizumab , Carboplatin,albumin-bound paclitaxel Patients receive Pembrolizumab 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 4 cycles in the absence of disease progression or unacceptable toxicity. Then surgery.

Drug: Pembrolizumab+Carboplatin+albumin-bound paclitaxel:4 courses

2 courses arm

ACTIVE COMPARATOR

Drug:Pembrolizumab , Carboplatin,albumin-bound paclitaxel Patients receive Pembrolizumab 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 2 cycles in the absence of disease progression or unacceptable toxicity. Then surgery.

Drug: Pembrolizumab+Carboplatin+albumin-bound paclitaxel:2 courses

Interventions

Pembrolizumab+Carboplatin+albumin-bound paclitaxel:4 courses DRUG

Pembrolizumab,+Carboplatin+albumin-bound paclitaxel Pembrolizumab (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: Pembrolizumab, Carboplatin, albumin-bound paclitaxel:4 cycles

4 courses arm

Pembrolizumab+Carboplatin+albumin-bound paclitaxel:2 courses DRUG

Pembrolizumab,+Carboplatin+albumin-bound paclitaxel Pembrolizumab (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: Pembrolizumab , Carboplatin, albumin-bound paclitaxel:2 cycles

2 courses arm

Eligibility Criteria

• Age: 18 Years - 75 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 head and neck squamous cell carcinoma with the following stages: T3 or T4, N0;
• 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 \> 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;
• The myocardial enzyme profile was within the normal range (if the researchers comprehensively judged that the simple laboratory abnormality was not clinically significant, it was also allowed to be included);

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:1) 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);
• Received live vaccine within 30 days prior to initial administration (cycle 1, day 1); Note: Inactivated injectable virus vaccine against seasonal influenza is permitted for 30 days prior to initial administration; But live attenuated influenza vaccines administered intranasally are not allowed.
• Pregnant or lactating women;

Sponsors & Collaborators

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

Study Sites (1)

Sun yat-sen memorial hospital

Guangzhou, Guangdong, 510000, China

RECRUITING

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck; Mouth Neoplasms

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

Jinsong Li, MD

CONTACT

008618583879908; caobleat@hotmail.com

Haotian Cao, MD

CONTACT

Study Design

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

Study Record Dates

• First Submitted: June 5, 2023
• First Posted: August 8, 2023
• Study Start: April 4, 2023
• Primary Completion: April 3, 2025
• Study Completion (Estimated): April 3, 2030
• Last Updated: September 7, 2023

Record last verified: 2023-09

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)