Trial Title:
A Prospective, Randomised Controlled, Phase II Clinical Study of Tirilizumab in Combination With Albumin-bound Paclitaxel With Cisplatin for Neoadjuvant and Adjuvant Treatment of Locally Advanced Resectable Oral Squamous Cell Carcinoma
NCT ID:
NCT06470217
Condition:
Locally Advanced Head and Neck Squamous Cell Carcinoma
Conditions: Official terms:
Carcinoma
Carcinoma, Squamous Cell
Squamous Cell Carcinoma of Head and Neck
Paclitaxel
Albumin-Bound Paclitaxel
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:
tirilizumab with albumin-bound paclitaxel and cisplatin
Description:
tirilizumab administered by intravenous drip (no prophylaxis required) at a fixed dose of
200 mg. each infusion was given for 30 min (not less than 20 min and not more than 60
min) every 3 weeks, and 3 preoperative cycles of albumin-bound paclitaxel 260 mg/m2 and
cisplatin 75 mg/m2 on d1, with 1 cycle every 21 days; 3 preoperative Cycles. After
neoadjuvant therapy, patients underwent surgery and were stratified according to
pathological conditions after surgery; if significant pathological remission (MPR) was
achieved, 6 cycles of adjuvant therapy with tirilizumab monotherapy (concurrent
radiochemotherapy was available for those with high-risk factors) were performed; if MPR
was not achieved, concurrent radiochemotherapy was performed.
Arm group label:
Neoadjuvant treatment arm
Other name:
neoadjuvant arm
Intervention type:
Procedure
Intervention name:
surgery
Description:
patients underwent direct surgical treatment, with postoperative radiotherapy or
radiochemotherapy depending on the presence or absence of histological or pathological
high-risk factors.
Arm group label:
Standard treatment arm
Other name:
Standard treatment arm
Summary:
The dosing regimen in the trial group was: tirilizumab with albumin-bound paclitaxel and
cisplatin for 3 preoperative Cycles. After neoadjuvant therapy, patients underwent
surgery and were stratified according to pathological conditions after surgery; if
significant pathological remission (MPR) was achieved, 6 cycles of adjuvant therapy with
tirilizumab monotherapy (concurrent radiochemotherapy was available for those with
high-risk factors) were performed; if MPR was not achieved, concurrent radiochemotherapy
was performed.
Control regimen: patients underwent direct surgical treatment, with postoperative
radiotherapy or radiochemotherapy depending on the presence or absence of histological or
pathological high-risk factors.
Detailed description:
The dosing regimen in the trial group was: tirilizumab administered by intravenous drip
(no prophylaxis required) at a fixed dose of 200 mg. each infusion was given for 30 min
(not less than 20 min and not more than 60 min) every 3 weeks, and 3 preoperative cycles
of albumin-bound paclitaxel 260 mg/m2 and cisplatin 75 mg/m2 on d1, with 1 cycle every 21
days; 3 preoperative Cycles. After neoadjuvant therapy, patients underwent surgery and
were stratified according to pathological conditions after surgery; if significant
pathological remission (MPR) was achieved, 6 cycles of adjuvant therapy with tirilizumab
monotherapy (concurrent radiochemotherapy was available for those with high-risk factors)
were performed; if MPR was not achieved, concurrent radiochemotherapy was performed.
Control regimen: patients underwent direct surgical treatment, with postoperative
radiotherapy or radiochemotherapy depending on the presence or absence of histological or
pathological high-risk factors.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
Age 18-75 years, male or female; Patients with primary stage III-IVa surgically
resectable squamous cell carcinoma of the oral cavity with measurable lesions (≥10 mm on
spiral CT scan, fulfilling RECIST 1.1 criteria) as confirmed by pathohistology; ECOG
score of 0 or 1; Expected survival ≥ 12 weeks; Tumour tissue (paraffin specimen or fresh
tumour tissue less than 2 years old) for PD-L1 detection is available; Organ function
levels must meet the following requirements (14 days prior to first dose of study drug)
Bone Marrow:Absolute Neutrophil Count (ANC) ≥ 1.5 x 109/L, Platelet (PLT) ≥ 100 x 109/L,
Haemoglobin (HB) ≥ 9g/dL (no blood transfusion or receipt of component blood within 14
days prior to the test); Liver: serum total bilirubin (TBIL) ≤ 1.5 times the upper limit
of normal, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5
times the upper limit of normal (if there is hepatic metastasis, AST and ALT are allowed
to be ≤ 5 times the upper limit of normal); and Kidney: blood creatinine level less than
1.5 times the upper limit of normal or creatinine clearance ≥60ml/min, urea nitrogen
≤200mg/L; Thyroid-stimulating hormone (TSH) ≤1×ULN (if abnormal, FT3 and FT4 levels
should be examined at the same time; if FT3 and FT4 levels are normal, they can be
enrolled) Urine protein ≤1+, if urine protein >1+, 24-hour urine protein measurement
should be collected, and its total amount should be ≤1g; and Normal cardiac function,
i.e. normal ECG or abnormalities without clinical significance and left ventricular
ejection fraction (LVEF) >50% on cardiac ultrasound.
Reproductively active female subjects must have a negative serum pregnancy test prior to
the first dose of the test drug.
Reproductively active male or female subjects must be using a highly effective method of
contraception (e.g., oral contraceptive pill, intrauterine device, abstinence from sexual
intercourse, or barrier method of contraception combined with spermicide) throughout the
course of the trial and continue to use contraception for 90 days after completion of
treatment; Subjects volunteered to join the study, signed an informed consent form, were
compliant and co-operated with follow-up visits.
Exclusion Criteria:
With distant metastatic lesions or localised lesions without indication for surgery
(stage IVb or IVc patients); Prior history of a primary tumour of nasopharyngeal
carcinoma; Patients who have participated or are participating in a clinical trial of
another drug/therapy within 4 weeks prior to the first dose of study drug; Major surgical
procedure performed/received within 4 weeks prior to the first dose of study drug or have
not recovered from the side effects of this procedure, live vaccination, immunotherapy,
radiotherapy within 2 weeks; Concurrently receiving any other anti-tumour therapy;
Patient has any active autoimmune disease or history of autoimmune disease (e.g., the
following, but not limited to: autoimmune hepatitis, interstitial pneumonitis, uveitis,
enteritis, hepatitis, pituitary gland inflammation, vasculitis, nephritis,
hyperthyroidism; vitiligo that does not require systemic therapy may be included; asthma
that has been in complete remission in childhood and does not require any intervention in
adulthood may be be included; asthma in which the patient requires medical intervention
with bronchodilators cannot be included); Patients who are on immunosuppressive, or
systemic hormone therapy for immunosuppression (dose >10mg/day prednisone or other
equipotent hormone) and continue to do so within 2 weeks prior to enrolment; History of
other malignancies within the past 5 years, except cured basal cell carcinoma of the
skin, squamous cell carcinoma of the skin, early stage prostate cancer, and carcinoma in
situ of the cervix; Patients who have received haematopoietic stimulating factors, such
as those receiving granulocyte colony-stimulating factor (G-CSF), erythropoietin, etc.,
within 1 week prior to the first dose of study drug; Prior treatment with
PD-1/PD-L1/PD-L2/CTLA-4 antibodies or activating or inhibitory drugs targeting T-cell
receptors (e.g., OX40, CD137); Positive HIV antibody or syphilis spirochete antibody test
results; Patients with active Hepatitis B or Hepatitis C:. If HBsAg or HBcAb is positive,
HBV DNA (results above the upper limit of the normal range).
If HCV antibody test result is positive, add HCV RNA (result above upper limit of normal
range); Known hypersensitivity to recombinant humanised PD-1 monoclonal antibody drugs
and their components; and Active lung disease (interstitial pneumonitis, pneumonia,
obstructive lung disease, asthma) or a history of active tuberculosis; Have any
uncontrolled clinical problems, including but not limited to. Persistent or active
(serious) infections. Medication-uncontrolled hypertension (blood pressure persistently
greater than 150/90 mmHg); Poorly controlled diabetes mellitus. Heart disease (class
III/IV congestive heart failure or heart block as defined by the New York Heart
Association).
The following within 6 months prior to first dose: deep vein thrombosis or pulmonary
embolism; myocardial infarction; severe or unstable arrhythmia or angina pectoris;
percutaneous coronary intervention, acute coronary syndrome, coronary artery bypass
grafting; cerebrovascular accidents, transient ischaemic attacks, cerebral embolism;
Previous stem cell transplant or organ transplant; Persons with a history of psychotropic
substance abuse that they are unable to abstain from or persons with a history of
psychotic disorders; Other severe, acute, or chronic medical conditions or abnormal
laboratory tests that, in the investigator's judgement, may increase the risks associated
with participation in the study or may interfere with the interpretation of study
results; Patients who, in the judgement of the investigator, have poor compliance, or
other conditions that make participation in this trial unsuitable.
Gender:
All
Minimum age:
18 Years
Maximum age:
75 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
the Ninth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
Address:
City:
Shanghai
Zip:
200011
Country:
China
Status:
Recruiting
Contact:
Last name:
Yanan Wang, M.D.
Phone:
13764278464
Email:
wangyan_an@163.com
Start date:
June 19, 2024
Completion date:
June 19, 2027
Lead sponsor:
Agency:
Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University
Agency class:
Other
Source:
Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06470217
