Trial Title:
Neoadjuvant Toripalimab + Chemotherapy ± Cetuximab in Locally Advanced Head and Neck Squamous Cell Carcinoma (Neo-ICT)
NCT ID:
NCT06647563
Condition:
Squamous Cell Carcinoma of Head and Neck
Conditions: Official terms:
Carcinoma
Carcinoma, Squamous Cell
Squamous Cell Carcinoma of Head and Neck
Paclitaxel
Carboplatin
Cetuximab
Albumin-Bound Paclitaxel
Antibodies
Immunoglobulins
Conditions: Keywords:
Programmed Cell Death-1 (PD1, PD-1)
Head and Neck Squamous Cell Carcinoma
Toripalimab
Albumin-bound paclitaxel
Carboplatin
Cetuximab
Neoadjuvant
Study type:
Interventional
Study phase:
Phase 3
Overall status:
Not yet recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Biological
Intervention name:
Toripalimab
Description:
Specified dose on specified days
Arm group label:
Toripalimab + Chemotherapy + Cetuximab + SOC (Immunotherapy+ chemotherapy+targeted therapy, ICT)
Arm group label:
Toripalimab + Chemotherapy + SOC (Immunotherapy+ chemotherapy, IC)
Other name:
PD-1 antibody
Intervention type:
Biological
Intervention name:
Cetuximab
Description:
Specified dose on specified days
Arm group label:
Toripalimab + Chemotherapy + Cetuximab + SOC (Immunotherapy+ chemotherapy+targeted therapy, ICT)
Other name:
EGFR antibody
Intervention type:
Drug
Intervention name:
Albumin-Bound Paclitaxel
Description:
Specified dose on specified days
Arm group label:
Toripalimab + Chemotherapy + Cetuximab + SOC (Immunotherapy+ chemotherapy+targeted therapy, ICT)
Arm group label:
Toripalimab + Chemotherapy + SOC (Immunotherapy+ chemotherapy, IC)
Intervention type:
Drug
Intervention name:
Carboplatin
Description:
Specified dose on specified days
Arm group label:
Toripalimab + Chemotherapy + Cetuximab + SOC (Immunotherapy+ chemotherapy+targeted therapy, ICT)
Arm group label:
Toripalimab + Chemotherapy + SOC (Immunotherapy+ chemotherapy, IC)
Intervention type:
Drug
Intervention name:
Cisplatin
Description:
Specified dose on specified days
Arm group label:
No Neoadjuvant + SOC (Control)
Arm group label:
Toripalimab + Chemotherapy + Cetuximab + SOC (Immunotherapy+ chemotherapy+targeted therapy, ICT)
Arm group label:
Toripalimab + Chemotherapy + SOC (Immunotherapy+ chemotherapy, IC)
Intervention type:
Radiation
Intervention name:
Radiotherapy 60 Gray/day
Description:
Low risk participants administered 2 Gray/day in 30 fractions. Administered using
intensity modulated radiation therapy.
Arm group label:
No Neoadjuvant + SOC (Control)
Arm group label:
Toripalimab + Chemotherapy + Cetuximab + SOC (Immunotherapy+ chemotherapy+targeted therapy, ICT)
Arm group label:
Toripalimab + Chemotherapy + SOC (Immunotherapy+ chemotherapy, IC)
Intervention type:
Radiation
Intervention name:
Radiotherapy 66 Gray/day
Description:
High risk participants administered 2 Gray/day in 33 fractions. Administered using
intensity modulated radiation therapy.
Arm group label:
No Neoadjuvant + SOC (Control)
Arm group label:
Toripalimab + Chemotherapy + Cetuximab + SOC (Immunotherapy+ chemotherapy+targeted therapy, ICT)
Arm group label:
Toripalimab + Chemotherapy + SOC (Immunotherapy+ chemotherapy, IC)
Intervention type:
Radiation
Intervention name:
Radiotherapy 70 Gray/day
Description:
Participants with gross residual disease administered 2 Gray/day in 35 fractions.
Administered using intensity modulated radiation therapy.
Arm group label:
No Neoadjuvant + SOC (Control)
Arm group label:
Toripalimab + Chemotherapy + Cetuximab + SOC (Immunotherapy+ chemotherapy+targeted therapy, ICT)
Arm group label:
Toripalimab + Chemotherapy + SOC (Immunotherapy+ chemotherapy, IC)
Summary:
This study is a randomized, active-controlled, open-label clinical trial for participants
with newly diagnosed Stage III-IVb, resectable, locoregionally advanced head and neck
squamous cell carcinoma (LA-HNSCC). The study consists of two experimental arms and one
control arm. Participants in Experimental Arm A will receive two cycles of Toripalimab,
albumin-bound paclitaxel, carboplatin, and cetuximab prior to surgery. Participants in
Experimental Arm B will receive two cycles of Toripalimab, albumin-bound paclitaxel, and
carboplatin before surgical intervention. Following the surgical procedure, individuals
in both Experimental Arm A and B will continue to receive 15 cycles of Toripalimab. The
Control Arm will undergo the current standard treatment without preoperative drug
intervention. Postoperatively, participants will be administered postoperative
radiotherapy or chemoradiotherapy based on their recurrence risk. The primary study
hypotheses are that the treatments in the Experimental Arms will improve the 2-year
event-free survival (EFS) rates compared to the standard control treatment.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Histologically confirmed squamous cell carcinoma of the head and neck (excluding
nasopharyngeal cancer);
2. Male or female, aged 18-75 years;
3. Clinical stage III-IVb (AJCC 8th edition TNM stage) and operable patients; if
oropharyngeal squamous cell carcinoma (P16-), the stage is III-IVb; if oropharyngeal
squamous cell carcinoma (P16+), the stage is III;
4. No prior antitumor therapy including radiotherapy, chemotherapy, immunotherapy or
biological therapy for the current tumor;
5. Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1;
6. Life expectancy ≥ 6 months;
7. No obvious contraindications to immunotherapy, radiochemotherapy, or surgical
treatment;
8. Willing to accept surgical treatment;
9. The level of main organ function meets the following criteria:
1. Routine blood tests: WBC ≥ 4.0 × 10^9/L, ANC ≥ 1.5 × 10^9/L, PLT ≥ 100 ×
10^9/L, Hb ≥ 90 g/L (no blood transfusion or blood products within 14 days, no
correction with G-CSF and other hematopoietic growth factors);
2. Biochemical assessments: serum albumin ≥ 3.0 g/dL (30 g/L), TBIL ≤ 1.5 × ULN,
ALT, AST ≤ 2.5 × ULN, BUN and CRE ≤ 1.5 × ULN or creatinine clearance ≥ 60
mL/min (Cockcroft-Gault formula);
3. Adequate coagulation function: defined as international normalized ratio (INR)
or prothrombin time (PT) ≤ 1.5 × ULN; If the subject is receiving anticoagulant
therapy, PT should be within the proposed therapeutic range of the
anticoagulant;
10. Women of childbearing potential must have a negative pregnancy test result (serum or
urine), conducted within seven days prior to enrollment and agree to use effective
contraception during the study period and for six months post last dose of anti-PD-1
antibody administration. Male subjects with female partners who are capable of
conception must also utilize effective contraception throughout this study duration
and for six months after their final dose anti-PD-1 antibody;
11. Willingness to participate in this study by signing an informed consent form, while
exhibiting strong compliance and readiness to cooperate with follow-up procedures.
Exclusion Criteria:
1. Previous treatment with anti-PD-1/PD-L1 antibody, anti-PD-L2 antibody, anti-CD137
antibody, anti-CTLA-4 antibody, or other drugs/antibodies targeting T cell
co-stimulation or checkpoint pathway;
2. Active autoimmune disease. Subjects in stable condition who do not require systemic
immunosuppressive therapy are permitted; examples include type I diabetes mellitus,
hypothyroidism requiring only hormone replacement therapy, and skin conditions that
do not necessitate systemic treatment (e.g., vitiligo, psoriasis, alopecia).
3. Patients with congenital or acquired immunodeficiency (e.g., HIV infection), active
hepatitis B (HBV-DNA ≥ 10^4 copies/ml) or hepatitis C (positive antibody for HCV,
and HCV-RNA above the lower limit of detection of the analytical procedure);
4. Known allergy to the study drug or any of its excipients; or serious allergic
reaction to other monoclonal antibodies.
5. The occurrence of any of the following conditions within 6 months prior to
randomization: myocardial infarction, severe/unstable angina pectoris, NYHA class II
or higher cardiac insufficiency, clinically significant supraventricular or
ventricular arrhythmias, and symptomatic congestive heart failure.
6. Vaccination with live vaccines within 4 weeks prior to the first dose of the study
drug. Inactivated virus vaccine can be administered for seasonal flu, but not
attenuated live influenza vaccines administered intranasally.
7. Known history of allogeneic organ transplant or allogeneic stem cell transplant.
8. The history of drug addiction and the abuse of psychoactive substances.
9. Pregnant or breastfeeding women.
10. Any other malignant neoplasm diagnosed within 5 years prior to study entry, except
for carcinoma that is amenable to local treatment and has been cured, such as basal
cell carcinoma or squamous cell carcinoma of the skin, superficial bladder cancer,
cervical carcinoma in situ, carcinoma in situ of breast ductal, and papillary
thyroid cancer.
11. Patients with other significant physical or mental health conditions, or laboratory
test abnormalities that may elevate the risk of participation in the study or
compromise the integrity of the study results, as determined by the investigators,
are deemed unsuitable for participation in this study.
Gender:
All
Minimum age:
18 Years
Maximum age:
75 Years
Healthy volunteers:
No
Start date:
November 1, 2024
Completion date:
September 30, 2030
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/NCT06647563
