Toripalimab Plus Surgery vs Surgery Alone for Resectable Recurrent Nasopharyngeal Carcinoma

Toripalimab Plus Surgery vs Surgery Alone for Resectable Recurrent Nasopharyngeal Carcinoma: a Prospecitve, Parallel, Multicenter, Phase III, Randomized Clinical Trial

Through multicenter, open-label, randomised clinical trials, we intend to demonstrate that PD-1 treatment added to salvage surgery could further decrease the rate of disease progression and improve the survival outcome of patients with resectable locally recurrent nasopharyngeal carcinoma compared with those treated with salvage surgery alone.

Study Overview

• Status: Recruiting
• Conditions: Nasopharyngeal Carcinoma; Surgery; PD-1
• Intervention / Treatment: Drug: Toripalimab; Procedure: salvage surgery

Detailed Description

Through multicenter, open-label, randomised clinical trials, patients with resectable locally recurrent nasopharyngeal carcinoma are randomized into salvage surgery plus PD-1 treatment group and salvage surgery alone group. The efficacy and safety of patients between these two groups are compared.

• Study Type: Interventional
• Enrollment (Anticipated): 218
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: You-Ping Liu, MD, PhD; Phone Number: 86-20-87343379; Email: liuyoup@sysucc.org.cn

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510060
      • Recruiting
      • Sun Yat-sen University Cancer Center
    • Guangzhou, Guangdong, China, 510515
      • Not yet recruiting
      • NanFang Hospital of Southern Medical University
      • Contact: Hao-Cheng Tang, MD.PhD; Phone Number: 86-15920115552; Email: hctang2006@qq.com
    • Guangzhou, Guangdong, China, 510080
      • Not yet recruiting
      • The First Affiliated Hospital, Sun Yat-sen University
    • Guangzhou, Guangdong, China, 510700
      • Not yet recruiting
      • The Fifth Affiliated Hospital of Guangzhou Medical University
    • Guangzhou, Guangdong, China, 528000
      • Not yet recruiting
      • The First People's Hospital of Foshan
      • Contact: Jun Tang, MD; Phone Number: 86-18038860199; Email: tjun@fsyyy.com
    • Zhongshan, Guangdong, China, 528403
      • Not yet recruiting
      • Zhongshan People's Hospital
      • Contact: Min-Yi Fu; Phone Number: 86-13924933366; Email: 503498362@qq.com
  • Jiangxi
    • Nanchang, Jiangxi, China, 330008
      • Not yet recruiting
      • The Tenth Affiliated Hospital, Sun Yat-Sen University
      • Contact: Ming-Yuan Chen, MD, PhD; Phone Number: 86-13903052650; Email: chmingy@mail.sysu.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. The recurrence time is more than 6 months from the end of radiotherapy.
2. Histologically confirmed recurrent nasopharyngeal carcinoma.
3. Resectable nasopharyngeal diseases: recurrent T1 (the tumor is confined in nasopharynx, oropharynx and/or nasal cavity without parapharyngeal involvement); recurrent T2 (the tumor is confined in the superficial parapharyngeal spacer and is more than 0.5cm far from the internal carotid artery) and recurrent T3 (the tumor is confined in the base wall of the sphenoid sinus and is more than 0.5cm far from the internal carotid artery and cavernous sinus). (according to the 8th edition of American Joint Committee on Cancer (AJCC) staging system for nasopharyngeal carcinoma)
4. Resectable recurrent regional lymph node diseases (recurrent N1-3) without prevertebral fascia, cervical vertebrae, or common/internal carotid artery involvement. (according to the 8th edition of AJCC staging system)
5. Given written informed consent.

Exclusion Criteria:

1. Karnofsky Performance Status (KPS) ≤70.
2. Has severe medical disorder, important organ dysfunction, and/or a substantial history of mental illness.
3. Has known subjects with other malignant tumors.
4. Has participated in other drug trials within 3 months of planned start of study treatment.
5. Received a systematic or local glucocorticoid therapy within 4 weeks of planned start of study treatment.
6. Suffered from diseases need long-term treatment with immunosuppressive drugs, or required systematic or local glucocorticoid therapy with immunosuppressive doses.
7. Prior therapy with a PD-1, anti-PD-Ligand 1 (PD-L1) or cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) agent.
8. Has active autoimmune disease (e.g., uveitis, enteritis, hepatitis, hypophysitis, nephritis, vasculitis, hyperthyroidism, and asthma requiring bronchodilator therapy). Patients with skin disease that doesn't require systemic treatment (e.g., vitiligo, psoriasis, or alopecia) will be allowed to enroll.
9. Has a known history of human immunodeficiency virus (HIV), has hepatitis B surface antigen (HBsAg) positive with hepatitis B virus (HBV) DNA copy number of ≥1000cps/ml or hepatitis C virus (HCV) antibody positive.
10. Has received a live vaccine within 4 weeks of planned start of study treatment.
11. Pregnancy or breast feeding.
12. Cannot complete regular follow-up.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Toripalimab plus salvage surgery; Toripalimab: Toripalimab treatment before and after salvage surgery.; Salvage surgery: endoscopic nasopharyngectomy for recurrent nasopharyngeal tumor, and selective neck dissection for recurrent regional lymph node.	Drug: Toripalimab; Toripalimab: 240 mg, intravenous injection over 60 minutes (Q3W); Toripalimab should be completed for 2 cycles at 1-2 weeks before surgery, and continually applied since 1-2 weeks after surgery until confirmed disease progression, death, unacceptable toxicity, withdrawal of consent, investigator decision, or 1 year.; Other Names: PD-1 antibody; Procedure: salvage surgery; Endoscopic nasopharyngectomy is used for recurrent nasopharyngeal tumor and selective neck dissection for recurrent regional lymph node.
ACTIVE_COMPARATOR: Salvage surgery alone; 1. Salvage surgery: endoscopic nasopharyngectomy for recurrent nasopharyngeal tumor, and selective neck dissection for recurrent regional lymph node.	Procedure: salvage surgery; Endoscopic nasopharyngectomy is used for recurrent nasopharyngeal tumor and selective neck dissection for recurrent regional lymph node.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease-free survival	Defined as the time interval from randomization to disease progression or death due to any cause, whichever come first.	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate	Defined as the proportion of patients with radiologically confirmed complete or partial response according to RECIST 1.1.	3-5 weeks
Major Pathological Response Rate	Defined as the proportion of patients with no more than 10% viable tumor cells which is identified on routine hematoxylin and eosin staining within the recurrent nasopharyngeal tumor and/or regional lymph node after neoadjuvant PD-1 treatment.	4-6 weeks
Overall Survival	Defined as the time interval from randomization to death due to any cause.	2 years
Distant Metastasis-Free Survival	Defined as the time interval from randomisation to the date of first distant metastases.	2 years
Locoregional Relapse-Free Survival	Defined as the time from randomisation to the date of first locoregional relapse.	2 years
Score of survival quality according to the EORTC Quality of Life Questionnaire (QLQ)-C30 (V3.0)	Score of survival quality according to the EORTC Quality of Life Questionnaire (QLQ)-C30 (V3.0) before treatment, during treatment, after treatment.	up to 2 years
Score of survival quality according to the EORTC Quality of Life Questionnaire Head and Neck (The QLQ-H&N35)	Score of survival quality according to the EORTC Quality of Life Questionnaire Head and Neck (The QLQ-H&N35) before treatment, during treatment, after treatment.	up to 2 years

Collaborators and Investigators

• Sponsor: Sun Yat-sen University
• Collaborators: First Affiliated Hospital, Sun Yat-Sen University; Nanfang Hospital of Southern Medical University; First People's Hospital of Foshan; Zhongshan People's Hospital, Guangdong, China; Tenth Affiliated Hospital, Sun Yat-sen University

Study record dates

Study Major Dates

• Study Start (ACTUAL): March 3, 2021
• Primary Completion (ANTICIPATED): March 3, 2025
• Study Completion (ANTICIPATED): March 3, 2033

Study Registration Dates

• First Submitted: February 25, 2021
• First Submitted That Met QC Criteria: February 28, 2021
• First Posted (ACTUAL): March 3, 2021

Study Record Updates

• Last Update Posted (ACTUAL): March 4, 2021
• Last Update Submitted That Met QC Criteria: March 3, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Keywords: Recurrent; Nasopharyngeal carcinoma; Disease free survival; Salvage surgery; Anti-programmed death-1 antibody
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Head and Neck Neoplasms; Nasopharyngeal Diseases; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases; Nasopharyngeal Neoplasms; Carcinoma; Nasopharyngeal Carcinoma
• Other Study ID Numbers: SYSUCC-CMY-2020-2302

Drug and device information, study documents

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