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).

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
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

Spots Global Cancer Trial Database for three cycles (toripalimab + cetuximab + platinum)