Neoadjuvant PD-1 Inhibitor Combined With Cetuximab in Operable Locally Advanced HNSCC

NCT05993858 | Not Yet Recruiting Phase 2

• 1 other identifier: UHCT230527
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Head and Neck Squamous Cell Carcinoma; Neoadjuvant Therapy

Outcome Measures

Primary Outcomes (1)

• Pathological Complete Response (pCR) Rate evaluated by investigators

  pCR rate is defined as the percentage of participants having an absence of residual invasive cancer in resected tumour and lymph nodes following completion of neoadjuvant therapy.

  up to 13 weeks after neoadjuvant

Secondary Outcomes (6)

• 2 years Event-free survival (EFS) Rate evaluated by investigators

  EFS Up to 3 years

• Incidence of AEs/SAEs

  Up to 3 years

• Objective Response Rate (ORR) evaluated by investigators

  Up to 3 years

• Major Pathological Response (MPR) Rate evaluated by investigators

  up to 13 weeks after neoadjuvant

• 2 years Disease-free survival (DFS) Rate evaluated by investigators

  DFS Up to 3 years

Other Outcomes (2)

• Exploratory analysis of the tumor microenvironment related with the outcome

  Up to 3 years

• Exploratory analysis of potential biomakers related with the outcome

  Up to 3 years

Study Arms (1)

Neoadjuvant therapy+Surgery+Adjuvant therapy+Consolidation therapy

OTHER

Participants receive totally 3 cycles of neoadjuvant therapy (Toripalimab+cetuximab), then radical treatment(surgery). After surgery, Participants receive radiotherapy or chemoradiotherapy according to the pathological results of the operation. Then, participants receive consolidation therapy of Toripalimab.

Drug: 3cycles (Toripalimab + cetuximab); Procedure: Surgery; Radiation: Radiotherapy or chemoradiotherapy

Interventions

3cycles (Toripalimab + cetuximab) DRUG

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.

Neoadjuvant therapy+Surgery+Adjuvant therapy+Consolidation therapy

Surgery PROCEDURE

After neoadjuvant therapy, patients would accept surgery within 11-13 weeks.

Neoadjuvant therapy+Surgery+Adjuvant therapy+Consolidation therapy

Radiotherapy or chemoradiotherapy RADIATION

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.

Neoadjuvant therapy+Surgery+Adjuvant therapy+Consolidation therapy

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Union Hospital, Tongji Medical College, Huazhong University of Science and Technology: lead

Study Sites (1)

Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

Wuhan, Hebei, 430000, China

Location

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck

Interventions

toripalimab; Cetuximab; Surgical Procedures, Operative; Radiotherapy; Chemoradiotherapy

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Head and Neck Neoplasms; Neoplasms by Site

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Therapeutics; Combined Modality Therapy; Drug Therapy

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 19, 2023
• First Posted: August 15, 2023
• Study Start: October 20, 2023
• Primary Completion: December 20, 2025
• Study Completion (Estimated): December 20, 2026
• Last Updated: August 15, 2023

Record last verified: 2023-07

Locations

CN (1)