The Management of Metastatic Neck Nodes in N2/3 Hypopharyngeal Squamous Cell Carcinoma

The Management of Metastatic Neck Nodes in N2/3 Hypopharyngeal Squamous Cell Carcinoma: A Multi-center Randomized Controlled Prospective Study

This is a multi-center, multidisciplinary, open-label, randomized controlled prospective clinical study.

Study Overview

• Status: Recruiting
• Conditions: Hypopharyngeal Carcinoma
• Intervention / Treatment: Drug: Docetaxel; Drug: Cisplatin; Drug: Capecitabine; Radiation: Concomitant chemoradiotherapy; Procedure: Surgery

Detailed Description

Hypopharyngeal squamous cell carcinoma (HPSCC) is prone to have regional metastasis, which is an established negative prognostic factor. Especially for N2/3 patients whose metastatic neck nodes are bulky and have multiple or extracapsular spreads, their survival outcome is even worse. Therefore, it is vital for clinicians to select proper treatment and further improve the prognosis of N2/3 HPSCC patients. The aim of this randomized controlled prospective study is to explore the suitable treatment strategy of metastatic neck nodes in N2/3 HPSCC. This study will enroll a total of 111 HPSCC patients, who are clinically classified as T1/2 N2/3 M0 stage and initially treated with surgery (group 1) or induction chemotherapy (group 2). For patients with the regional response of PR<50%/SD/PD after induction chemotherapy, their following treatment will be surgery for both the primary and regional sites. For patients with the regional response of CR/PR≥50%, the following treatment will be concomitant chemoradiotherapy for both the primary and regional sites.

• Study Type: Interventional
• Enrollment (Anticipated): 111
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Feiran Li; Phone Number: 8621-64377151; Email: lifr214@163.com

Study Locations

• China
  • Heilongjiang
    • Harbin, Heilongjiang, China, 150000
      • Not yet recruiting
      • Harbin Medical University Cancer Hospital
      • Contact: Susheng Miao, PhD; Email: 38898546@qq.com
  • Shandong
    • Jinan, Shandong, China, 250012
      • Not yet recruiting
      • Shandong Provincial ENT Hospital, Cheeloo College of Medicine, Shandong University
      • Contact: Zhenghua Lv, PhD; Email: entlvzhenghua@163.com
  • Shanghai
    • Shanghai, Shanghai, China, 200031
      • Recruiting
      • Eye & ENT Hospital, Fudan University
      • Contact: Ming Zhang, PhD; Phone Number: 8621-64377151; Email: ent_zhm@126.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Able to understand and willing to sign a written informed consent document.
2. Age ≥ 18 and ≤ 75 years.
3. Male or female.
4. Karnofsky physical status (KPS): ≥ 80
5. Hepatic function, renal function and normal blood test. Hepatic function: Alanine aminotransferase (ALT) ≤ 2.5 upper limit of normal, Aspartate aminotransferase (AST) ≤ 2.5 upper limit of normal. Serum total bilirubin ≤ 1.5 upper limit of normal. Kidney function: Serum creatinine < upper limit of normal value and creatinine clearance rate > 60 ml/(min*1.73m2) (Cockcroft-Gault formula). Blood test: neutrophil (Neu) ≥ 1.5×109/L, platelet (PLT) ≥ 100×109/L, hemoglobin (HGB) ≥ 90 g/L.
6. Pathologically diagnosed with squamous cell carcinoma of the hypopharynx.
7. After clinical and radiographic evaluations, clinically classified as T1/2 N2/3 M0 stage according to American Joint Committee on Cancer (AJCC, eighth edition).
8. Resectable regional metastatic lesion (incompletely tumor- wrapped carotid vascular).
9. Assessable tumor lesions according to Response Evaluation Criteria in Solid Tumors (RECIST, Version 1.1).
10. Radical treatment intent.
11. Male patients with fertility and female patients with fertility and pregnancy risk must agree to use contraceptive methods throughout the study period, and continued until at least 6 months after the last dose of cisplatin. Female patients who do not have fertility (ie meet at least one of the following criteria): Have undergone hysterectomy and/or bilateral oophorectomy with archival records, medically confirmed ovarian function decline; In postmenopausal state. It is defined as: At least 12 months of continuous menstruation without other pathological or physiological reasons, and the status confirmed by serum follicle stimulating hormone (FSH) levels is consistent with postmenopausal status.
12. Good compliance.

Exclusion Criteria:

1. Distant metastatic disease
2. Have a history of other cancers or coinstantaneous second primary tumor
3. Previous treatment for the primary tumor, including radiotherapy, surgery except biopsy operation, chemotherapy, immunotherapy and biological targeted therapy.
4. Patients who have participated in other clinical trials within 1 month before the test.
5. Patients estimated to have poor tolerance to induction chemotherapy.
6. The investigator believes that it is inappropriate for individuals to participate in the trial: having, for example, severe acute or chronic medical conditions (including immune colitis, inflammatory bowel disease, non-infectious pneumonia, pulmonary fibrosis) or mental illness (including recent time [within the past year] or active suicidal ideation or behavior).
7. Palliative treatment intent.
8. Pregnant or lactating women.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Induction chemotherapy group; Patients initially receive induction chemotherapy consisting of docetaxel, cisplatin and capecitabine (TPC), q3w, 2-3 cycles in total. Patients with regional response of complete reaction (CR)/partial reaction (PR)≥50% after induction chemotherapy then receive concomitant chemoradiotherapy for both the primary and regional sites. Patients with regional response of PR<50%/stable disease (SD)/progressive disease (PD) after induction chemotherapy then receive surgery for both the primary and regional sites and postoperative concomitant chemoradiotherapy.	Drug: Docetaxel; 60 mg/m2 i.v. day 1; Drug: Cisplatin; 60 mg/m2 i.v. day 1-3; Drug: Capecitabine; 750 mg/m2 po bid day 1-14; Radiation: Concomitant chemoradiotherapy; Radiotherapy: using intensity-modulated radiation therapy (IMRT) Gross tumor volume (GTV) for primary tumor: 66-70 Gy in total, 2.0~2.2 Gy per day, 5 days per week Clinical target volume (CTV) for lesions closely related to the primary lesion and metastatic lymph nodes: 65~70 Gy in total, 1.7~2.0 Gy per day, 5 days per week Prophylactic irradiation for sites of suspected subclinical spread: 50~60 Gy in total, 1.7~2.0 Gy per day, 5 days per week Concurrent chemotherapy: cisplatin 80 mg/m2 on days 1-3 every 3 weeks.; Procedure: Surgery; Neck dissection and primary tumor resection
Active Comparator: Surgery group; Patients initially receive surgery for both the primary and regional sites and postoperative concomitant chemoradiotherapy.	Radiation: Concomitant chemoradiotherapy; Radiotherapy: using intensity-modulated radiation therapy (IMRT) Gross tumor volume (GTV) for primary tumor: 66-70 Gy in total, 2.0~2.2 Gy per day, 5 days per week Clinical target volume (CTV) for lesions closely related to the primary lesion and metastatic lymph nodes: 65~70 Gy in total, 1.7~2.0 Gy per day, 5 days per week Prophylactic irradiation for sites of suspected subclinical spread: 50~60 Gy in total, 1.7~2.0 Gy per day, 5 days per week Concurrent chemotherapy: cisplatin 80 mg/m2 on days 1-3 every 3 weeks.; Procedure: Surgery; Neck dissection and primary tumor resection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival rate	The proportion of patients with disease progress or death due to any reasons.	3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival rate	The proportion of dead patients due to any reasons.	3 years
Local control	The proportion of patients with local recurrence.	3 years
Regional control	The proportion of patients with regional recurrence.	3 years
Metastasis-free survival	The proportion of patients with distant metastasis.	3 years
Quality of life (UW-QOL V4.0)	Evaluated by University of Washington Quality of Life Questionnaire (UW-QOL) V4.0.	3 years
Adverse events	Evaluated by the NCI Common Terminology Criteria for Adverse Events (NCI-CTCAE) V5.0.	3 years

Collaborators and Investigators

• Sponsor: Eye & ENT Hospital of Fudan University
• Collaborators: Shandong Provincial Hospital; Harbin Medical University Third Affiliated Hospital
• Investigators: Principal Investigator: Ming Zhang, PhD, Eye & ENT Hospital, Fudan University

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2022
• Primary Completion (Anticipated): November 1, 2025
• Study Completion (Anticipated): November 1, 2025

Study Registration Dates

• First Submitted: August 6, 2022
• First Submitted That Met QC Criteria: August 6, 2022
• First Posted (Actual): August 9, 2022

Study Record Updates

• Last Update Posted (Actual): April 18, 2023
• Last Update Submitted That Met QC Criteria: April 17, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Keywords: Induction Chemotherapy; Metastatic Neck Nodes; Neck Dissection
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Head and Neck Neoplasms; Neoplasms, Squamous Cell; Carcinoma; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Docetaxel; Capecitabine
• Other Study ID Numbers: EENTHN0706

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No