Neoadjuvant vs Adjuvant in Locally Advanced Recurrent NPC

Neoadjuvant-Adjuvant Versus Adjuvant-Only Therapy Combined With Endoscopic Surgery in Advanced Recurrent Nasopharyngeal Carcinoma:A Multicenter Randomized Controlled Trial

A multicenter randomized controlled study of surgery combined with neoadjuvant and adjuvant therapy for locally advanced recurrent nasopharyngeal carcinoma in comparison to surgery combined with adjuvant therapy

Study Overview

• Status: Recruiting
• Conditions: Recurrent Nasopharyngeal Carcinoma
• Intervention / Treatment: Procedure: endoscopic surgery; Drug: Adjuvant therapy in control group,Toripalimab Injection and Gemcitabine based therapy; Drug: Neoadjuvant therapy,Toripalimab Injection and Gemcitabine based therapy; Drug: Adjuvant therapy in experimental group,Toripalimab Injection and Gemcitabine based therapy

Detailed Description

Eligible patients are randomized into the control group and the experimental group.

Patients in the experimental group would be administrated 2 courses of neoadjuvant therapy before surgery.After endoscopic surgery, patients would continue to receive 2-4 courses of chemotherapy and 8 courses of immunotherapy.

Patients in the control group would firstly receive endoscopic surgery, followed by chemotherapy and immunotherapy. In total, 4 to 6 courses of chemotherapy and 10 courses of immunotherapy would be administrated.

• Study Type: Interventional
• Enrollment (Estimated): 154
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Xiaole Song; Phone Number: +8621 64377134; Email: jxfxsxl@163.com

Study Locations

• China
  • Fuzhou, China
    • Not yet recruiting
    • Fujian Medical University Union Hospital
    • Principal Investigator: Desheng Wang
    • Contact: Desheng Wang
    • Sub-Investigator: Haichun Lai
  • Nanning, China
    • Recruiting
    • The People's Hospital of Guangxi Zhuang Autonomous Region
    • Principal Investigator: Shenhong Qu
    • Contact: Shenhong Qu
    • Sub-Investigator: Jingjin Weng
  • Shanghai, China
    • Not yet recruiting
    • Shanghai Zhongshan Hospital
    • Contact: Xinsheng Huang
    • Principal Investigator: Xinsheng Huang
    • Principal Investigator: Xianhui Ning
    • Principal Investigator: Lei Zhou
  • Shanghai, China
    • Not yet recruiting
    • Changhai Hospital
    • Contact: Haihong Tang
    • Principal Investigator: Haihong Tang
    • Sub-Investigator: Hongliang Zheng
    • Sub-Investigator: Haopu Li
    • Sub-Investigator: Fengya Pan
  • Shanghai, China
    • Not yet recruiting
    • Shanghai Sixth People's Hospital
    • Contact: Weitian Zhang
    • Principal Investigator: Weitian Zhang
    • Sub-Investigator: Ru Tang
  • Shenzhen, China
    • Not yet recruiting
    • Shenzhen Second People's Hospital
    • Contact: Yongtian Lu
    • Principal Investigator: Yongtian Lu
    • Principal Investigator: Jing Tao
  • Shanghai
    • Shanghai, Shanghai, China, 200031
      • Recruiting
      • Eye& ENT Hospital, Fudan University
      • Contact: Xiaole Song; Phone Number: 15821388769; Email: jxfxsxl@163.com
      • Principal Investigator: Hongmeng Yu
      • Sub-Investigator: Li Yan
      • Sub-Investigator: Xiaole Song
      • Sub-Investigator: Yuting Lai

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Pathologically diagnosed with recurrent nasopharyngeal carcinoma;
2. Resectable disease staging rT2 (deep parapharyngeal space, or distance to the internal carotid ≤5mm) or rT3 (excluding the lesions confined to the basal wall of sphenoid sinus), rT4, according to AJCC 8th edition;
3. Cervical lymph node metastasis can be controlled locally;
4. Aged 18 to 75 years;
5. Informed consent forms signed to participate in the trial;
6. Without distant metastasis;
7. ≥6months from the accomplishment of radical radiation to recurrence
8. previously only 1 course of radiotherapy;
9. Sufficient organ function;
10. ECOG score 0-2 and can tolerate surgery,chemotherapy and immunotherapy.

Exclusion Criteria:

1. Participate in other interventional clinical trials;
2. Uncontrolled illnesses that interfere with the therapy;
3. Suffering from another or multiple malignancy within 5 years (excluding fully treated basal cell or skin squamous cell carcinoma, cervical carcinoma in situ, etc.);
4. Any contradiction to surgery;
5. With serious autoimmune disease;
6. The patient is currently using immunosuppressive agents or systemic hormone therapy to achieve immunosuppressive effects (dosage>10mg/day prednisone or other glucocorticoids), and continues to use them within 2 weeks before the first administration;
7. Severe allergic reactions to other monoclonal antibodies;
8. History of radioactive particle planting;
9. Vaccination with live vaccine within 4 weeks prior to initial administration or possibly during the study period;
10. Female patients who are at pregnancy or lactation;
11. Other situations that the researchers believe not suitable for enrollment

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: The control group; Endoscopic surgery + adjuvant therapy	Procedure: endoscopic surgery; The tumor was resected by endoscopic nasopharyngectomy.; Drug: Adjuvant therapy in control group,Toripalimab Injection and Gemcitabine based therapy; Ten courses of Toripalimab Injection and four to six courses of chemotherapy,or until unacceptable side effects.
Experimental: The experimental group; Neoadjuvant therapy +endoscopic surgery + adjuvant therapy	Procedure: endoscopic surgery; The tumor was resected by endoscopic nasopharyngectomy.; Drug: Neoadjuvant therapy,Toripalimab Injection and Gemcitabine based therapy; Two courses of Toripalimab Injection and two courses of Toripalimab Injection and Gemcitabine based chemotherapy were given before endoscopic surgery.; Drug: Adjuvant therapy in experimental group,Toripalimab Injection and Gemcitabine based therapy; Eight courses of Toripalimab Injection and two to four courses of chemotherapy, or until unacceptable side effects.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
EFS	Event free survival	From randomization and any events(like:progression or toxic effects precluding surgery;inability to resect all gross disease; progression;surgical complications precluding initiation of adjuvant therapy; recurrence;death) up to 1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
OS	Overall Survival	Time interval of randomization and death of any cause, up to 5 years
DFS	Disease free survival	From randomization to recurrence, metastasis or death, up to 1 year
LRFS	Local recurrence free survival	From randomization to local recurrence or death, up to 1 year
DMFS	Distant metastasis free survival	From randomization to distant metastasis or death, up to 1 year
pCR	pathologic complete response	Time point of pathological tumor evaluation after sugery, around 2 weeks after sugery
ORR	Objective response rate,Proportion of CR, PR in all patients.	Time point of imaging evaluation before treatment(or randomization) and before surgery,up to 1 year
DCR	Disease Control Rate,Proportion of CR, PR and SD in all patients.	Time point of imaging evaluation before treatment(or randomization) and before surgery,up to 1 year
DoR	Duration of response,the time from the first assessment of the tumour as CR or PR to the first assessment of PD or death from any cause (whichever event occurs first).	First date of response to the date of progression, up to 5 years
1-and 2-year PFS rate	one- and two-year progression free survival rate	one- and two-year
1-and 2-year OS rate	one- and two-year overall survival rate	one- and two-year

Collaborators and Investigators

• Sponsor: Eye & ENT Hospital of Fudan University
• Collaborators: Changhai Hospital; Shanghai Zhongshan Hospital; Fujian Medical University Union Hospital; Shenzhen Second People's Hospital; Shanghai 6th People's Hospital; People's Hospital of Guangxi Zhuang Autonomous Region

Study record dates

Study Major Dates

• Study Start (Actual): July 9, 2024
• Primary Completion (Estimated): June 30, 2027
• Study Completion (Estimated): June 30, 2027

Study Registration Dates

• First Submitted: December 21, 2023
• First Submitted That Met QC Criteria: January 23, 2024
• First Posted (Actual): January 31, 2024

Study Record Updates

• Last Update Posted (Actual): June 3, 2025
• Last Update Submitted That Met QC Criteria: May 28, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Stomatognathic Diseases; Pathologic Processes; Neoplasms by Site; Neoplasms; Disease Attributes; Neoplasms by Histologic Type; Head and Neck Neoplasms; Neoplasms, Glandular and Epithelial; Otorhinolaryngologic Diseases; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Nasopharyngeal Diseases; Pharyngeal Diseases; Nasopharyngeal Neoplasms; Nasopharyngeal Carcinoma; Recurrence; Carcinoma; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Gemcitabine
• Other Study ID Numbers: adv-rNPC-RCT-Neo-V1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No