Neoadjuvant Toripalimab + Chemotherapy ± Cetuximab in Locally Advanced Head and Neck Squamous Cell Carcinoma (Neo-ICT)

NCT ID: NCT06647563

Last Updated: 2024-10-18

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

NOT_YET_RECRUITING

Clinical Phase

PHASE3

Total Enrollment

355 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-11-01

Study Completion Date

2030-09-30

Brief Summary

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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.

Detailed Description

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Conditions

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Squamous Cell Carcinoma of Head and Neck

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Toripalimab + Chemotherapy + Cetuximab + SOC (Immunotherapy+ chemotherapy+targeted therapy, ICT)

Participants will receive an intravenous (IV) infusion of Toripalimab 240mg on Day 1, Albumin-bound Paclitaxel 125mg/m\^2 on Days 1 and 8, Carboplatin with an area under the curve (AUC) of 5 on Day 1, and Cetuximab 400mg/m\^2 on Day 1, followed by Cetuximab 250mg/m\^2 on Day 1 of each subsequent week. The treatment is given in 21-day cycles for a total of two cycles. Afterward, participants will proceed to the standard of care (SOC), which includes surgical intervention and postoperative radiotherapy. Following surgical resection, high-risk participants will receive standard radiotherapy plus Cisplatin 100 mg/m\^2 via intravenous infusion on Day 1, every 3 weeks (Q3W) for three 21-day cycles. Low-risk participants will receive only standard radiotherapy. Subsequently, participants will receive Toripalimab 240mg every 21-day cycle for a total of 15 cycles.

Group Type EXPERIMENTAL

Toripalimab

Intervention Type BIOLOGICAL

Specified dose on specified days

Cetuximab

Intervention Type BIOLOGICAL

Specified dose on specified days

Albumin-Bound Paclitaxel

Intervention Type DRUG

Specified dose on specified days

Carboplatin

Intervention Type DRUG

Specified dose on specified days

Cisplatin

Intervention Type DRUG

Specified dose on specified days

Radiotherapy 60 Gray/day

Intervention Type RADIATION

Low risk participants administered 2 Gray/day in 30 fractions. Administered using intensity modulated radiation therapy.

Radiotherapy 66 Gray/day

Intervention Type RADIATION

High risk participants administered 2 Gray/day in 33 fractions. Administered using intensity modulated radiation therapy.

Radiotherapy 70 Gray/day

Intervention Type RADIATION

Participants with gross residual disease administered 2 Gray/day in 35 fractions. Administered using intensity modulated radiation therapy.

Toripalimab + Chemotherapy + SOC (Immunotherapy+ chemotherapy, IC)

Participants will receive an intravenous (IV) infusion of Toripalimab 240mg on Day 1, Albumin-bound Paclitaxel 125mg/m\^2 on Days 1 and 8, Carboplatin with an area under the curve (AUC) of 5 on Day 1. The treatment is given in 21-day cycles for a total of two cycles. Afterward, participants will proceed to the standard of care (SOC), which includes surgical intervention and postoperative radiotherapy. Following surgical resection, high-risk participants will receive standard radiotherapy plus Cisplatin 100 mg/m\^2 via intravenous infusion on Day 1, every 3 weeks (Q3W) for three 21-day cycles. Low-risk participants will receive only standard radiotherapy. Subsequently, participants will receive Toripalimab 240mg every 21-day cycle for a total of 15 cycles.

Group Type EXPERIMENTAL

Toripalimab

Intervention Type BIOLOGICAL

Specified dose on specified days

Albumin-Bound Paclitaxel

Intervention Type DRUG

Specified dose on specified days

Carboplatin

Intervention Type DRUG

Specified dose on specified days

Cisplatin

Intervention Type DRUG

Specified dose on specified days

Radiotherapy 60 Gray/day

Intervention Type RADIATION

Low risk participants administered 2 Gray/day in 30 fractions. Administered using intensity modulated radiation therapy.

Radiotherapy 66 Gray/day

Intervention Type RADIATION

High risk participants administered 2 Gray/day in 33 fractions. Administered using intensity modulated radiation therapy.

Radiotherapy 70 Gray/day

Intervention Type RADIATION

Participants with gross residual disease administered 2 Gray/day in 35 fractions. Administered using intensity modulated radiation therapy.

No Neoadjuvant + SOC (Control)

Participants will receive the standard of care (SOC) with no neoadjuvant prior to surgery. Following surgical resection, high-risk participants will receive standard radiotherapy plus Cisplatin 100 mg/m\^2 via intravenous infusion on Day 1, every 3 weeks (Q3W) for three 21-day cycles. Low-risk participants will receive only standard radiotherapy.

Group Type ACTIVE_COMPARATOR

Cisplatin

Intervention Type DRUG

Specified dose on specified days

Radiotherapy 60 Gray/day

Intervention Type RADIATION

Low risk participants administered 2 Gray/day in 30 fractions. Administered using intensity modulated radiation therapy.

Radiotherapy 66 Gray/day

Intervention Type RADIATION

High risk participants administered 2 Gray/day in 33 fractions. Administered using intensity modulated radiation therapy.

Radiotherapy 70 Gray/day

Intervention Type RADIATION

Participants with gross residual disease administered 2 Gray/day in 35 fractions. Administered using intensity modulated radiation therapy.

Interventions

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Toripalimab

Specified dose on specified days

Intervention Type BIOLOGICAL

Cetuximab

Specified dose on specified days

Intervention Type BIOLOGICAL

Albumin-Bound Paclitaxel

Specified dose on specified days

Intervention Type DRUG

Carboplatin

Specified dose on specified days

Intervention Type DRUG

Cisplatin

Specified dose on specified days

Intervention Type DRUG

Radiotherapy 60 Gray/day

Low risk participants administered 2 Gray/day in 30 fractions. Administered using intensity modulated radiation therapy.

Intervention Type RADIATION

Radiotherapy 66 Gray/day

High risk participants administered 2 Gray/day in 33 fractions. Administered using intensity modulated radiation therapy.

Intervention Type RADIATION

Radiotherapy 70 Gray/day

Participants with gross residual disease administered 2 Gray/day in 35 fractions. Administered using intensity modulated radiation therapy.

Intervention Type RADIATION

Other Intervention Names

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PD-1 antibody EGFR antibody

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University

OTHER

Sponsor Role lead

Responsible Party

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Yue He, MD

M.D.

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Yue He, M.D.

Role: PRINCIPAL_INVESTIGATOR

Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine

Central Contacts

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Feng Liu, M.D.

Role: CONTACT

18917797783

Other Identifiers

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JYKQ-2024-105

Identifier Type: -

Identifier Source: org_study_id

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