- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05980702
4 Courses vs 2 Courses of Pembrolizumab Combined With Carboplatin and Albumin-binding Paclitaxel of Neoadjuvant Therapy in HNSCC (HNC-SYSU-002)
Safety and Efficacy of Four Courses of Pembrolizumab Combined With Carboplatin and Albumin-binding Paclitaxel Versus Two Courses of Neoadjuvant Therapy in Patients With Resectable Head and Neck Squamous Cell Carcinoma (T3 or T4, N0) : An Optimal Efficacy Study (Prospective, Two-arm, Phase II)
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
- The event-free survival (EFS) of the two groups were compared;
- The main pathological response rate (MPR) of the two groups were compared;
- pTR of the two groups was compared;
- Overall survival (OS) of the two groups was compared;
- The radiological responses of the two groups were compared;
- 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.
Study Overview
Status
Conditions
Study Type
Enrollment (Estimated)
Phase
- Phase 2
Contacts and Locations
Study Contact
- Name: Jinsong Li, MD
- Phone Number: 008618583879908
- Email: caobleat@hotmail.com
Study Contact Backup
- Name: Haotian Cao, MD
Study Locations
-
-
Guangdong
-
Guangzhou, Guangdong, China, 510000
- Recruiting
- Sun Yat-sen Memorial Hospital
-
Principal Investigator:
- Jinsong Li, MD
-
Contact:
- Haotian Cao, MD
- Phone Number: 008618583879908
- Email: caobleat@hotmail.com
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Adult
- Older Adult
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- 18 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 > 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);
- For female subjects of childbearing age, a urine or serum pregnancy test should be tested negative within 3 days prior to receiving the first study drug administration (day 1 of Cycle 1). If the urine pregnancy test results cannot be confirmed negative, a blood pregnancy test is requested. Women of non-reproductive age were defined as at least one year after menopause or having undergone surgical sterilization or hysterectomy;
- If there is a risk of conception, all subjects (male or female) shall use contraception with an annual failure rate of less than 1% for the entire duration of treatment up to 120 days after the last study drug administration (or 180 days after the last chemotherapeutic drug administration).
Exclusion Criteria:
- 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 < 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;
There is any serious or uncontrolled systemic disease, such as:
- The resting electrocardiogram (ECG) presents significant and severely uncontrollable abnormalities in rhythm, conduction or morphology, such as complete left bundle branch block, Ⅱ degree or above heart block, ventricular arrhythmia or atrial fibrillation;
- Unstable angina pectoris, congestive heart failure, and NYHA grade ≥ 2 chronic heart failure;
- Any arterial thrombosis, embolism or ischemia, such as myocardial infarction, unstable angina pectoris, cerebrovascular accident or transient ischemic attack, occurred within 6 months before treatment;
- Poor blood pressure control (systolic > 140 mmHg, diastolic > 90 mmHg);
- A history of non-infectious pneumonia requiring glucocorticoid therapy or clinically active interstitial lung disease within 1 year prior to initial administration;
- Active pulmonary tuberculosis;
- There is an active or uncontrolled infection that requires systemic treatment;
- Clinically active diverticulitis, abdominal abscess, gastrointestinal obstruction;
- Liver diseases such as cirrhosis, decompensated liver disease, acute or chronic active hepatitis;
- Poor diabetes control (fasting blood glucose (FBG) > 10mmol/L);
- Urine routine indicated urine protein ≥++, and confirmed 24 hours urine protein quantity > 1.0 g;
- Patients with mental disorders and unable to cooperate with treatment;
- Medical history or evidence of disease that may interfere with test results, prevent participants from participating fully in the study, abnormal values of treatment or laboratory tests, or other conditions that the investigator considers unsuitable for enrollment. The Investigator considers other potential risks unsuitable for participation in the study.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: 4 courses arm
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.
|
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 |
Active Comparator: 2 courses arm
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.
|
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 |
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Percentage of adverse events graded by CTCAE v5.0
Time Frame: Time Frame: 90 days after surgery
|
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)
Time Frame: 6 weeks
|
The absence rate(Percentage) of invasive/in situ cancer and/or axillary lymph nodes.Change From Baseline from 6 weeks.
|
6 weeks
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Event-free survival (EFS)
Time Frame: 5 years
|
In cancer, the length(measured by months) of time after primary treatment for a cancer ends that the patient remains free of certain complications or events that the treatment was intended to prevent or delay.
|
5 years
|
Overall survival(OS)
Time Frame: 5 years
|
The time(measured by months) from day 1 of study treatment until death from any cause.
|
5 years
|
Operation delay rate
Time Frame: 2 months
|
Rate(percentage) of patients with an Unplanned Delay to Surgery defined as any change to scheduled surgery date considered to be at least possibly related to neoadjuvant treatment.
|
2 months
|
Radiographic Response
Time Frame: 6 weeks
|
Radiographic response to treatment as defined by RECIST 1.1.
They are grouped by PR, CR,SD,PD.
|
6 weeks
|
Collaborators and Investigators
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Neoplasms
- Neoplasms by Site
- Head and Neck Neoplasms
- Stomatognathic Diseases
- Mouth Diseases
- Mouth Neoplasms
- Molecular Mechanisms of Pharmacological Action
- Antineoplastic Agents
- Tubulin Modulators
- Antimitotic Agents
- Mitosis Modulators
- Antineoplastic Agents, Phytogenic
- Antineoplastic Agents, Immunological
- Immune Checkpoint Inhibitors
- Carboplatin
- Paclitaxel
- Pembrolizumab
- Albumin-Bound Paclitaxel
Other Study ID Numbers
- SYSKY-2023-219-02
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Oral Cancer
-
Royal Surrey County Hospital NHS Foundation TrustCompleted
-
Centre Francois BaclesseTerminatedCancer | Cognitive Function | Compliance | Oral TherapiesFrance
-
University of WashingtonBlaze Bioscience Inc.RecruitingStage III Lip and Oral Cavity Cancer AJCC v8 | Oral Cavity Squamous Cell Carcinoma | Stage I Lip and Oral Cavity Cancer AJCC v8 | Stage II Lip and Oral Cavity Cancer AJCC v8 | Stage IVA Lip and Oral Cavity Cancer AJCC v8United States
-
National Cancer Institute (NCI)CompletedLip and Oral Cavity Cancer | Oropharyngeal Cancer | Tongue Cancer | Oral LeukoplakiaUnited States
-
National Cancer Institute (NCI)CompletedLip and Oral Cavity Cancer | Oropharyngeal Cancer | Tongue Cancer | Stage 0 Lip and Oral Cavity Cancer | Stage 0 Oropharyngeal CancerUnited States
-
Dana-Farber Cancer InstituteCompletedBreast Cancer | Gastrointestinal Cancer | Oral Cancer Directed Therapy | Oral ChemotherapyUnited States
-
Ohio State University Comprehensive Cancer CenterCompletedTongue Cancer | Lip and Oral Cavity Squamous Cell Carcinoma | Oral Cavity Verrucous Carcinoma | Stage 0 Lip and Oral Cavity CancerUnited States
-
University of British ColumbiaRecruiting
-
Centre Francois BaclesseLigue contre le cancer, FranceCompletedManagement of Oral Care and Cancer in Palliative SituationFrance
-
Istituto Scientifico Romagnolo per lo Studio e...Kessler FoundationUnknownCancer | Oral Drug AdministrationItaly
Clinical Trials on Pembrolizumab+Carboplatin+albumin-bound paclitaxel:4 courses
-
The First Affiliated Hospital of Guangzhou Medical...Unknown
-
Zhigang LiJiangsu HengRui Medicine Co., Ltd.Not yet recruitingLocally Advanced Resectable Esophageal Squamous Cell CarcinomaChina
-
Sun Yat-Sen Memorial Hospital of Sun Yat-Sen UniversityRecruitingHead and Neck Squamous Cell Carcinoma | Oral CancerChina
-
Hao LongActive, not recruitingNon Small Cell Lung CancerChina
-
Peking University First HospitalMerck Sharp & Dohme LLCNot yet recruitingAdvanced Non-squamous Non-small-cell Lung Cancer | Metastatic Non-squamous Non Small Cell Lung Cancer | Recurrent Non-Squamous Non-Small Cell Lung CancerChina
-
Fondazione IRCCS Istituto Nazionale dei Tumori,...CompletedMetastatic Urothelial CarcinomaItaly
-
Liaoning Tumor Hospital & InstituteNot yet recruitingNon Small Cell Lung Cancer
-
CelgeneCompletedNon-Small Cell Lung Cancer (NSCLC)Russian Federation
-
Jiuda ZhaoRecruiting
-
CelgeneTerminatedOvarian Neoplasms | Fallopian Tube Neoplasms | Peritoneal NeoplasmsUnited States