Trial Title:
Neoadjuvant Immunochemotherapy for LAOSCC
NCT ID:
NCT06258811
Condition:
Oral Squamous Cell Carcinoma
Locally Advanced Head and Neck Carcinoma
Conditions: Official terms:
Carcinoma
Carcinoma, Squamous Cell
Squamous Cell Carcinoma of Head and Neck
Paclitaxel
Tislelizumab
Conditions: Keywords:
Oral squamous cell carcinoma
Neoadjuvant immunochemotherapy
Study type:
Interventional
Study phase:
Phase 3
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Intervention model description:
Randomized 1:1 to experimental or control arm. Experiment arm: neoadjuvant
immunochemotherapy (2 cycles, and 21 days each cycle, 260mg/m2 albuminpaclitaxel
intravenously on day 1 and day 22, with 75mg/m2 of cisplatin and 200mg of tislelizumab) +
radical surgery + adjuvant therapy (radiation/chemoradiation followed by 200mg of
tislelizumab, every 3 weeks for one year) Control arm: standard therapy of radical
surgery +adjuvant therapy (radiation/chemoradiation)
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
albumin paclitaxel, cispatin, tislelizumab
Description:
Neoadjuvant immunochemotherapy (2 cycles, and 21 days each cycle, 260mg/m2 albumin
paclitaxel intravenously on day 1 and day 22, with 75mg/m2 of cisplatin and 200mg of
tislelizumab) + radical surgery + adjuvant therapy (radiation/chemoradiation followed by
200mg of tislelizumab, every 3 weeks for one year)
Arm group label:
Experimental arm
Summary:
To evaluate the prognostic efficacy of neoadjuvant immunochemotherapy with tislelizumab,
albumin paclitaxel and cisplatin followed by radical surgery and adjuvant therapy
compared with standard therapy for patients with locally advanced and resectable oral
squamous cell carcinoma.
Detailed description:
Neoadjuvant therapy (NAT) is regarded as an effective way to reduce or downgrade the
locally advanced or aggressive cancers, and to improve the chance of eradication of the
locoregional lesions by radical surgery and/or radiotherapy. However, there are still
debates on the clinical value of NAT for patients with locally advanced oral squamous
cell carcinoma (LAOSCC). In a series of clinical trials on neoadjuvant therapy for LAOSCC
have been carried out by our research group, the pathological efficacy of neoadjuvant
immunochemotherapy is superior to neoadjuvant immunotarget therapy, neoadjuvant
chemotarget therapy, or neoadjuvant chemotherapy. And in the neoadjuvant
immunochemotherapy clinical trial (NCT04473716), the results of the safety and efficacy
of neoadjuvant regimen showed that the neoadjuvant regimen of immunochemotherapy was well
tolerated, with an MPR rate of 60% and 2-year OS of 90%, which were better than
previously reported patients receiving standard treatment for LAOSCC. However, limited to
single-arm clinical trial, the patients with LAOSCC benefit from neoadjuvant
immunochemotherapy for survival, randomized controlled trials with larger sample size are
needed. The aim of present trial is to evaluate the prognostic efficacy of 2-year
survival rate in patients with LAOSCC receiving neoadjuvant immunochemotherapy with
tiralizumab, albumin paclitaxel and cisplatin followed by radical surgery and adjuvant
therapy compared with standard therapy.
The patients with LAOSCC would receive NAT with tiralizumab, albumin paclitaxel and
cisplatin followed by radical surgery and adjuvant therapy (the experimental group) or
radical surgery and adjuvant therapy (the control group). A total number of 134 patients
will be recruited. Neoadjuvant immunochemotherapy: for the patients who are randomly
assigned to the experimental group, the palpable edges of the primary lesion (both the
longest and shortest axis) would be marked before NAT by at least four points, which is
0.5cm away; 260mg/m2 albuminpaclitaxel intravenously on day 1 and day 22, with 75mg/m2 of
cisplatin at an hour interval and 200mg of tislelizumab at an hour interval will be
performed. NAT will be given every 3 weeks for 2 cycles, unless there is disease
progression, unacceptable toxic effects, or withdrawal of consent by the patients.
Surgery will be performed within 2 weeks after completion of NAT. Surgery: Radical
resection of the primary lesion and full neck dissection with proper reconstruction will
be performed. The safety margins of the primary lesion are 1.0-1.5cm far away from the
palpable margins of the lesion; for patients who received NAT, the safety margins are
1.0cm away from the marks that were placed before NAT, to ensure the same extent surgery
in both groups. Post-operative adjuvant therapy: radiotherapy will be arranged 4 to 6
weeks after surgery. Routine external beam radiotherapy, will be performed, and the dose
is 1.8-2Gy/day, 5 days/week for 6 weeks, and totally 54-60Gy, in the patient with high
risk features, concurrent chemotherapy with cisplatin of 80mg/m2 will be used; in the
experimental group, adjuvant maintaining therapy of 200mg of tislelizumab, every 3 weeks,
for one year will be used. A complete medical history will be obtained and tumor
assessment will be performed at baseline. Clinical tumor response will be assessed by
clinical evaluation, imaging evaluation will be characterized according to the criteria
of response evaluation criteria in solid tumors (version 1.1) before surgery.
Post-operative pathological response will be assessed by post-operative pathological
examination. Patients will be followed-up by every three months in the first 2 years,
every six months in the next 3-5 years, and once a year thereafter until death or data
censoring. Overall survival will be calculated from the date of randomization to the date
of death; event free survival will be calculated from the date of randomization to local
recurrence, regional recurrence, distant metastasis, disease progress, or death; disease
free survival will be calculated from the date of randomization to tumor recurrence or
distant metastasis or death from any cause.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Eastern Cooperative Oncology Group (ECOG) performance status (PS): 0-1
2. Histopathological diagnosis of oral squamous cell carcinoma (including tongue, gums,
cheek, floor of mouth, hard palate, and posterior molar region)
3. Primary tumor with a clinical stage of III/IVA (T1-2/N1-2/M0 or T3-4a/cN0-2/M0, AJCC
2018)
4. Patients must have at least one measurable lesion according to the Response
Evaluation Criteria in Solid Tumors (RECIST v1.1)
5. Blood routine: white blood cells (WBCs) >3,000/mm3, hemoglobin >8 g/L, platelets
>80,000/mm3
6. Liver function: alanine amino transferase/aspartate amino transferase (ALAT/ASAT)
<2.5 times the upper limit of normal and bilirubin <1.5 times the upper limit of
normal
7. Renal function: Serum creatinine <1.5 times the upper limit of normal
8. Coagulation function: INR、PT、APTT<1.5 times the upper limit of normal
9. Signed the informed consent form
Exclusion Criteria:
1. Unresolved grade 2 [(Common Terminology Criteria for Adverse Events (CTCAE 5.0)] or
higher toxic reactions caused by previous anticancer treatments
2. Known allergic reaction (grade 3-4) to any ingredients or excipients of the therapy
3. Known history of malignancy, unless been cured and no recurrence for 5 years
4. Known history of radiation to head and neck
5. Active severe clinical infection (> National Cancer Institute (NCI)-CTCAE version
5.0 grade 2 infection)
6. Obvious cardiovascular abnormalities [such as myocardial infarction, superior vena
cava syndrome, grade 2 or higher heart disease diagnosed according to the New York
Heart Association (NYHA) classification 3 months before enrollment]
7. Patients receiving immunology-based treatment for any reason
8. Patients with a history of active bleeding, coagulopathy, or receiving coumarin
anticoagulation therapy
9. Pregnant or lactating women
10. Known active hepatitis B or C. Active hepatitis B is defined as a known HBsA
positive with HBV DNA≥500 IU/mL. Active hepatitis C is defined as a known hepatitis
C antibody positive and a known amount of hepatitis C virus HCV RNA results greater
than the lower limit of detection. The presence of other serious liver diseases,
including chronic autoimmune liver disease, primary biliary cirrhosis or sclerosing
cholangitis, alcoholic liver disease, or non-alcoholic steatohepatitis (NASH)
11. Complicated with severe, uncontrolled infection or known human immunodeficiency
virus (HIV) infection, or diagnosed as acquired immunodeficiency syndrome (AIDS); or
uncontrolled autoimmune disease; or history of allogeneic tissue/organ
transplantation, stem cell or bone marrow transplantation, or solid organ
transplantation
12. Participation in other clinical trials within 30 days before enrollment
13. Other situations that the investigator considers unsuitable with respect to
participating in the trial
Gender:
All
Minimum age:
18 Years
Maximum age:
75 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Huashan Hospital, Fudan University
Address:
City:
Shanghai
Zip:
200040
Country:
China
Status:
Recruiting
Contact:
Last name:
Lai-ping Zhong, MD, PhD
Phone:
+862152888915
Email:
zhonglp@hotmail.com
Contact backup:
Last name:
Ying-ying Huang, MD
Phone:
+862152889999
Phone ext:
7182
Email:
kqyxyhyy@163.com
Investigator:
Last name:
Jing-song Li, MD, PhD
Email:
Principal Investigator
Investigator:
Last name:
Xue-kui Liu, MD, PhD
Email:
Principal Investigator
Investigator:
Last name:
Lei Tao, MD, PhD
Email:
Principal Investigator
Investigator:
Last name:
Yu Wang, MD, PhD
Email:
Principal Investigator
Investigator:
Last name:
Can-hua Jiang, MD, PhD
Email:
Principal Investigator
Investigator:
Last name:
Li-song Lin, MD, PhD
Email:
Principal Investigator
Investigator:
Last name:
Jian Meng, MD, PhD
Email:
Principal Investigator
Investigator:
Last name:
Qi Zhu, MD, PhD
Email:
Principal Investigator
Investigator:
Last name:
Ying-ying Huang, MD
Email:
Sub-Investigator
Start date:
February 20, 2024
Completion date:
December 30, 2028
Lead sponsor:
Agency:
Lai-ping Zhong
Agency class:
Other
Collaborator:
Agency:
Sun Yat-sen University
Agency class:
Other
Collaborator:
Agency:
Fudan University
Agency class:
Other
Collaborator:
Agency:
Central South University
Agency class:
Other
Collaborator:
Agency:
Fujian Medical University
Agency class:
Other
Source:
Huashan Hospital
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06258811
