Trial Title:
Neoadjuvant PD-1 Inhibitor Combined With Cetuximab in Operable Locally Advanced HNSCC
NCT ID:
NCT05993858
Condition:
Head and Neck Squamous Cell Carcinoma
Neoadjuvant Therapy
Conditions: Official terms:
Carcinoma
Carcinoma, Squamous Cell
Squamous Cell Carcinoma of Head and Neck
Cetuximab
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Not yet recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
3cycles (Toripalimab + cetuximab)
Description:
Toripalimab by intravenous (IV) infusion every 3 weeks (Q3W), 3 preoperative and 17
consolidated doses.
The preoperative starting dose of cetuximab is 400 mg/m^2 by IV infusion over 120 minutes
for 1 week, subsequently followed by 250 mg/m^2 IV infusion over 60 minutes, from week 2
to 9.
Arm group label:
Neoadjuvant therapy+Surgery+Adjuvant therapy+Consolidation therapy
Intervention type:
Procedure
Intervention name:
Surgery
Description:
After neoadjuvant therapy, patients would accept surgery within 11-13 weeks.
Arm group label:
Neoadjuvant therapy+Surgery+Adjuvant therapy+Consolidation therapy
Intervention type:
Radiation
Intervention name:
Radiotherapy or chemoradiotherapy
Description:
Adjuvant radiotherapy was given 4 weeks after surgery. Patients with positive
intraoperative pathological margins/extra lymph node envelope invasion are treated with
an additional cisplatin synchronous chemotherapy.
Arm group label:
Neoadjuvant therapy+Surgery+Adjuvant therapy+Consolidation therapy
Summary:
This is a single-center, single-arm, phase II clinical study to evaluate the efficacy and
safety of PD-1 inhibitor combined with cetuximab in neoadjuvant therapy for locally
advanced HNSCC.
Detailed description:
At present, the standard treatment for patients with operable locally advanced head and
neck squamous cell carcinoma (HNSCC) is adjuvant radiotherapy with or without
platinum-based synchronous chemotherapy after operation. However, the risk of recurrence,
metastasis and death remains high in this population with this intense combination
treatment regimen. Both EGFR monoclonal antibody and PD-1 inhibitors have proven the
effect in advanced HNSCC. At the same time, cetuximab and PD-1 inhibitors have been
reported to have a synergistic effect that may improve patient survival. This study aims
to explore the efficacy and safety of PD-1 inhibitor combined with cetuximab in
neoadjuvant therapy for locally advanced HNSCC.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- The age at the time of enrollment is more than 18 years old and less than 70 years
old, both male and female.
- Histologically diagnosed as squamous cell carcinoma of the mouth, oropharynx,
hypopharynx or larynx; preoperative evaluation can be surgically resected.
- Have the following high-risk recurrence conditions as defined in the 8th edition of
the American Joint Committee on Cancer [AJCC] Guidelines: a)HPV-negative disease,
stage III, IVa, according to the head and Neck Tumor/lymph node/metastasis (TNM)
guidelines; b)non-oropharyngeal HPV-positive disease, stages III, IVa, IVb,
according to head and neck TNM guidelines.
- No previous treatment for HNSCC.
- Have at least one evaluable target lesion according to RECIST version 1.1 criteria.
- The Eastern Cancer Cooperation Organization (ECOG) physical fitness score was 0 or
1.
- Major organs have normal function, the following criteria are met:
- The standard of blood routine examination（(not transfused or receiving component
blood within 14 days prior to testing)：hemoglobin (HB) ≥ 9g/dL；absolute neutrophil
count (ANC) ≥1.5×10^9/L, platelets (PLT) ≥100×10^9/L.
- Biochemical examination: serum total bilirubin (TBIL) <1.5 times the upper limit of
normal value(ULN); aspartate aminotransferase (AST) and alanine aminotransferase
(ALT)<2.5 ULN; serum creatinine≤ULN and endogenous creatinine clearance>50 mL/min
(Cockcroft-Gault formula) Gault formula).
- Signed written informed consent.
- Adhere to the research protocol judged by the investigator.
- female subjects of reproductive potential must have a negative serum pregnancy test
prior to the first dose of the trial drug.
- The male fertile patients and female fertile patients with pregnancy risk must
consent to the use of 2 contraceptive methods (at least one of which is considered
highly effective) throughout the study period.
- Patients who are willing and able to follow visit schedules, treatment plans,
laboratory tests, and other research procedures.
Exclusion Criteria:
- prior treatment with EGFR/PD-1/PD-L1/PD-L2/CD137/CTLA-4 antibodies(including
ipilimumab) or activating or inhibitory agents targeting T-cell receptors.
- Major surgery within 4 weeks before enrollment.
- Proven allergic to EGFR monoclonal antibody, PD-1 antibody or its excipients.
- Any active autoimmune disease or history of autoimmune disease (e.g., the following:
interstitial pneumonia, uveitis, enteritis, hepatitis, hypophysitis, vasculitis,
myocarditis, nephritis, hyperthyroidism, hypothyroidism (can be included after
effective hormone replacement therapy), etc; patients with vitiligo or asthma in
complete remission in childhood may be included, adults patients with asthma who do
not need any intervention and require medical intervention with bronchodilators may
be included) .
- Previous or co-existing malignancies (except those that have been cured and have
survived cancer-free for more than 5 years, such as basal cell carcinoma of the
skin, carcinoma in situ of the cervix, and papillary carcinoma of the thyroid).
- Failure to control cardiac clinical symptoms or disease, e.g., the following: a)
patients with NYHAII or above heart failure, b) unstable angina pectoris c) patients
with myocardial infarction within 1 year, d) patients with clinically significant
supraventricular or ventricular arrhythmias requiring clinical intervention.
- Subjects requiring systemic treatment with corticosteroids (> 10mg/ day prednisone
efficacy dose) or other immunosuppressants within 14 days prior to administration of
the study drug were allowed to use inhaled or topical steroids and adrenal hormone
replacement at a dose>10mg/day prednisone efficacy dose in the absence of active
autoimmune disease.
- Have active infections that require treatment.
- Have a congenital or acquired immune deficiency (such as HIV infection), active
hepatitis B (HBV-DNA≥10^3 copy number/ml), or hepatitis C (hepatitis C antibody
positive and HCV-RNA above the lower detection limit of analytical methods).
- The patient has received other treatment before.
- Had received live vaccine within 4 weeks prior to starting study treatment.
- A known history of psychotropic substance abuse, alcohol or drug use.
- Pregnant or lactating women.
- In the investigator's judgment, the subjects had other factors that might have led
to their forced discontinuation of the study, such as other serious medical
conditions (including mental illness) requiring concomitant treatment, serious
abnormalities in laboratory test values, or family or social factors that might have
affected the safety of the subjects or the circumstances of the trial data
collection.
- HNSCC Patients with T1/T2 or N0/N1.
- oral cancer, larynx cancer, hypopharyngeal cancer withT4b or N3 and
P16-oropharyngeal cancer.
- Have active pulmonary tuberculosis.
- Serious infections (including, but not limited to, hospitalization for complications
of infection, bacteremia, or severe pneumonia) that occurred within 4 weeks prior to
initiation of study treatment.
- Had received systemic immunostimulatory drugs (including but not limited to
interferon or interleukin-2 [IL-2]) within 4 weeks prior to initiation of study
therapy or remained within 5 drug half-lives (choice the longer of the two).
- Patients with recurrent peptic ulcers (e.g., gastric ulcers, duodenal ulcers), who
have a history of peptic ulcer complications such as perforation, bleeding,
obstruction, etc., or who have been assessed by clinicians as having a higher risk
of complications.
Gender:
All
Minimum age:
18 Years
Maximum age:
70 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
Address:
City:
Wuhan
Zip:
430000
Country:
China
Contact:
Last name:
Kunyu Yang, Doctor
Phone:
+86-13995595360
Email:
yangkunyu@hust.edu.cn
Start date:
October 20, 2023
Completion date:
December 20, 2026
Lead sponsor:
Agency:
Wuhan Union Hospital, China
Agency class:
Other
Source:
Wuhan Union Hospital, China
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05993858
