Trial Title:
4 Courses vs 2 Courses of Pembrolizumab Combined With Carboplatin and Albumin-binding Paclitaxel of Neoadjuvant Therapy in HNSCC
NCT ID:
NCT05980702
Condition:
HNSCC
Oral Cancer
PD-1
Conditions: Official terms:
Mouth Neoplasms
Paclitaxel
Albumin-Bound Paclitaxel
Carboplatin
Pembrolizumab
Conditions: Keywords:
HNSCC
Oral Cancer
PD-1
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Pembrolizumab+Carboplatin+albumin-bound paclitaxel:4 courses
Description:
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
Arm group label:
4 courses arm
Intervention type:
Drug
Intervention name:
Pembrolizumab+Carboplatin+albumin-bound paclitaxel:2 courses
Description:
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
Arm group label:
2 courses arm
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. The event-free survival (EFS) of the two groups were compared;
2. The main pathological response rate (MPR) of the two groups were compared;
3. pTR of the two groups was compared;
4. Overall survival (OS) of the two groups was compared;
5. The radiological responses of the two groups were compared;
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.
Criteria for eligibility:
Criteria:
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:
1. The absolute value of neutrophil granulocyte (ANC) ≥1.5x109/L in the last 14
days without the use of granulocyte colony stimulating factor;
2. Platelets ≥100×109/L without blood transfusion in the past 14 days;
3. Hemoglobin > without blood transfusion or use of erythropoietin within the
last 14 days; 9g/dL;
4. Total bilirubin ≤1.5× upper limit of normal value (ULN);
5. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5×ULN
(ALT or AST ≤5×ULN in patients with liver metastasis);
6. Serum creatinine ≤1.5×ULN and creatinine clearance (calculated by
Cockcroft-Gault formula) ≥60 ml/min;
7. Good coagulation function, defined as International Standardized ratio (INR) or
prothrombin time (PT) ≤1.5 times ULN;
8. 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;
9. 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);
10. 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;
11. 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:
1. 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;
2. Unstable angina pectoris, congestive heart failure, and NYHA grade ≥ 2 chronic
heart failure;
3. 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;
4. Poor blood pressure control (systolic > 140 mmHg, diastolic > 90 mmHg);
5. A history of non-infectious pneumonia requiring glucocorticoid therapy or
clinically active interstitial lung disease within 1 year prior to initial
administration;
6. Active pulmonary tuberculosis;
7. There is an active or uncontrolled infection that requires systemic treatment;
8. Clinically active diverticulitis, abdominal abscess, gastrointestinal
obstruction;
9. Liver diseases such as cirrhosis, decompensated liver disease, acute or chronic
active hepatitis;
10. Poor diabetes control (fasting blood glucose (FBG) > 10mmol/L);
11. Urine routine indicated urine protein ≥++, and confirmed 24 hours urine protein
quantity > 1.0 g;
12. 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.
Gender:
All
Minimum age:
18 Years
Maximum age:
75 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Sun yat-sen memorial hospital
Address:
City:
Guangzhou
Zip:
510000
Country:
China
Status:
Recruiting
Contact:
Last name:
Haotian Cao, MD
Phone:
008618583879908
Email:
caobleat@hotmail.com
Investigator:
Last name:
Jinsong Li, MD
Email:
Principal Investigator
Start date:
April 4, 2023
Completion date:
April 3, 2030
Lead sponsor:
Agency:
Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
Agency class:
Other
Source:
Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05980702
