Neoplasms

All Conditions

Rare Diseases

Carcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Hypopharyngeal Cancer

Antineoplastic Agents

All Drugs and Chemicals

Carboplatin

Cetuximab

Cisplatin

Antineoplastic Agents, Immunological

Participants receive three cycles of neoadjuvant therapy (toripalimab+cetuximab+platinum), followed by radical surgery. After surgery, participants receive radiotherapy or chemoradiotherapy according to the pathological results of the operation.

Cetuximab 250 mg/m2 i.v. qw (first loading dose 400 mg/m2) for nine doses; Toripalimab 240 mg/m2 i.v. d1, q21d, three cycles; Cisplatin 25 mg/m2 i.v. d1-3, q21d, three cycles or Carboplatin AUC 5 i.v. d1, q21d, three cycles (patients with cisplatin contraindications or renal impairment after cisplatin use).

three cycles (toripalimab + cetuximab + platinum)

The attending physician should select the appropriate surgical treatment and try to perform radical laryngeal preservation surgery for patients with tumor retraction after induction therapy. Patients who cannot preserve laryngeal function due to tumor load need to undergo total laryngeal resection. According to the scope of pharyngectomy, the surgical treatments include partial laryngopharyngectomy, total laryngectomy and partial pharyngectomy, total laryngopharyngectomy, and total pharyngo-laryngo-esophagectomy. Cervical lymph node dissection was performed when necessary.

Radical surgery

1. Using intensity-modulated radiotherapy (IMRT) technology, the dose of radiotherapy is determined according to whether there are adverse prognostic factors in the postoperative pathology, including positive margins, extracapsular invasion of lymph nodes, primary pT3 or T4, N2 lymph node lesions, peripheral nerve invasion, vascular/lymphatic infiltration.

   Primary site: residual GTV or tumor bed dose 60-70Gy: 1.8-2.12 Gy / fraction. Cervical lymph nodes or lymphatic drainage area: 56-70 Gy: 1.7-2.12 Gy / fraction.
2. Postoperative adjuvant concurrent chemotherapy regimen:

Cisplatin 25mg/m2 i.v. d1-3, d22-24 or Carboplatin AUC 5 i.v. d1, d22 (if cisplatin contraindications).

Radiotherapy or chemoradiotherapy

Lei Tao, PhD

Xiaoshen Wang, PhD

Lei Tao

The purpose of this clinical trial is to evaluate the efficacy and safety of immunotherapy combined with cetuximab and platinum neoadjuvant therapy in patients with resectable locally advanced hypopharyngeal cancer. Participants will receive three cycles of TPC neoadjuvant therapy (toripalimab+ cetuximab + platinum), radical surgery (laryngeal preservation surgery if possible), and sequential (chemo)radiotherapy treatment after surgery. This trial aims to answer the following questions:

1. pCR rate
2. MPR rate, ORR, LPR/DFS/OS rare at 1 and 2 years
3. Safety and quality of life

The standard treatment for patients with resectable hypopharyngeal carcinoma is surgery plus postoperative adjuvant radiotherapy or chemoradiotherapy. Growing evidence shows that neoadjuvant therapy may significantly increase pCR in locally advanced SCCHN patients, potentially improving patient survival. The development of drugs, immunotherapy, and targeted therapy has been proven to improve the overall survival of patients with SCCHN significantly, and PD-1 inhibitor combined with cetuximab has also shown promising efficacy in R/M SCCHN. This study explores the effectiveness and safety of immunotherapy combined with cetuximab and platinum neoadjuvant therapy in patients with resectable locally advanced hypopharyngeal carcinoma.

Neoadjuvant PD-1 Inhibitor Combined With Cetuximab and Platinum in Resectable Locally Advanced Hypopharyngeal Carcinoma

Neoadjuvant Therapy With Toripalimab Combined With Cetuximab and Platinum for Resectable Locally Advanced Hypopharyngeal Cancer

Refer to EORTC QLQ-C30 (version 3, version Chinese). After the end of treatment, it is assessed every 3 months (for patients after PD, subsequent quality of life assessment is no longer performed).

Peripheral blood samples and surgical tissue samples are retained for correlation analysis of PD-1/PD-L1 expression levels with efficacy and prognosis and screening for genes or markers related to efficacy and prognosis.

The pCR rate is defined as the percentage of participants who have no residual tumor cells in the resected primary tumor within 14 weeks after the start of neoadjuvant therapy.

MPR rate, defined as no more than 10% of residual viable tumor, evaluated by experienced pathologists.

The ORR is the proportion of patients whose tumor volume was reduced to 30% and sustained for more than 4 weeks as assessed by RECIST 1.1.

LPR is the proportion of patients who avoid total laryngectomy. 1-year and 2-year LPR is defined as the probability of larynx preservation for a patient at a given time (1 year and 2 years).

DFS is the time from enrollment until radiographic disease progression, local or distant recurrence, or death due to any cause. The 1-year and 2-year DFS rate is the probability of disease-free survival for a patient at a given time (1 year and 2 years).

OS is the time from enrollment to death due to any cause. The 1-year and 2-year OS rates are the probability of overall survival for a patient at a given time (1 year and 2 years).

Eye & ENT Hospital of Fudan University

Carcinoma, Squamous Cell

Squamous Cell Carcinoma of Head and Neck

Neoplasms, Squamous Cell

Head and Neck Neoplasms

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.

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.

3cycles (Toripalimab + cetuximab)

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

Surgery

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.

Kunyu Yang, Doctor

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.

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.

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

A Single-Center, Single-Arm Exploratory Clinical Trial of Neoadjuvant PD-1 Inhibitor Combined With Cetuximab in Operable Locally Advanced Head and Neck Squamous Cell Carcinoma

Exploratory analysis of the tumor microenvironment related to the outcome(including the number, function and metabolism of immune cells in tumor microenvironment).

Exploratory analysis of potential biomarkers related to the outcome (including PD-L1 expression in tissue specimen, tumor mutation burden (TMB), whole exome sequencing (WES) ,Single-cell RNA-sequencing (scRNA-seq) and Spatial transcriptomics (ST)).

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.

Event Free Survival (EFS): EFS is defined as the time from randomization until radiographic disease progression, local progression precluding surgery, inability to resect the tumor, local or distant recurrence, or death due to any cause. The 2y-EFS rate is defined as the probability of event-free survival for a patient at a given point in time (2 years).

Overall incidence of adverse events (AEs); incidence of grade 3 and above AEs; incidence of serious adverse events (SAEs).

The ORR was defined as proportion of patients whose tumor volume was reduced to 30% and sustained for more than 4 weeks as assessed by RECIST 1.1.

MPR rate is defined as the percentage of participants having ≤10% viable tumor cells in the resected primary tumor and all resected lymph nodes in neoadjuvant therapy.

DFS is defined as the time from postoperation until radiographic disease progression, local or distant recurrence, or death due to any cause. The 2y-DFS rate is defined as the probability of disease-free survival for a patient at a given point in time (2 years).

Organ retention rate is defined as the proportion of patients whose tumor avoids radical surgery.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Neoadjuvant PD-1 Inhibitor Combined With Cetuximab and Platinum in Resectable Locally Advanced Hypopharyngeal Carcinoma	NCT06151743	Locally Advance...	three cycles (t... Radical surgery Radiotherapy or...	18 Years - 75 Years	Eye & ENT Hospital of Fudan University
Neoadjuvant PD-1 Inhibitor Combined With Cetuximab and Platinum in Resectable Locally Advanced Hypopharyngeal Carcinoma	NCT06151743	Locally Advance...	three cycles (t... Radical surgery Radiotherapy or...	18 Years - 75 Years	Eye & ENT Hospital of Fudan University
Neoadjuvant PD-1 Inhibitor Combined With Cetuximab in Operable Locally Advanced HNSCC	NCT05993858	Head and Neck S... Neoadjuvant The...	3cycles (Toripa... Surgery Radiotherapy or...	18 Years - 70 Years	Wuhan Union Hospital, China
Neoadjuvant PD-1 Inhibitor Combined With Cetuximab in Operable Locally Advanced HNSCC	NCT05993858	Head and Neck S... Neoadjuvant The...	3cycles (Toripa... Surgery Radiotherapy or...	18 Years - 70 Years	Wuhan Union Hospital, China
Neoadjuvant PD-1 Inhibitor Combined With Cetuximab in Operable Locally Advanced HNSCC	NCT05993858	Head and Neck S... Neoadjuvant The...	3cycles (Toripa... Surgery Radiotherapy or...	18 Years - 70 Years	Wuhan Union Hospital, China

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