Induction Chemotherapy and Immunotherapy Combined Radiotherapy With or Without Concurrent Chemotherapy for Stage III-IVa NPC

Prospective Randomized Trial Comparing Induction Chemotherapy and Immunotherapy Combined Radiotherapy With or Without Concurrent Chemotherapy for Stage III-IVa Nasopharyngeal Carcinoma

The purpose of this study is to compare induction chemotherapy (gemcitabine+cisplatin) plus immunotherapy with concurrent chemoradiotherapy (CCRT) or RT alone in patients with stage III-IVa nasopharyngeal carcinoma(NPC), in order to confirm the value of Immunotherapy and concurrent chemotherapy in NPC patients.

Study Overview

• Status: Not yet recruiting
• Conditions: Nasopharyngeal Carcinoma
• Intervention / Treatment: Drug: without concurrent cisplatin chemotherapy; Drug: with concurrent cisplatin chemotherapy

Detailed Description

Patients Patients with stage III-Iva(except T3N0M0) non-keratinizing NPC (UICC/AJCC 8th edition) are randomly assigned to receive immunotherapy and induction chemotherapy plus CCRT or RT alone. Patients in both groups receive Anti-PD-1 Antibody, gemcitabine (1000 mg/m² d1,8) and cisplatin (80mg/m² d1) every 3 weeks for three cycles before CCRT. The immunotherapy and induction chemotherapy plus CCRT group receive cisplatin 80-100 mg/m² every 3 weeks for 2 cycles, concurrently with intensity-modulated radiotherapy (IMRT). IMRT is given as 2.0-2.30 Gy per fraction with five daily fractions per week for 6-7 weeks to a total dose of 66 Gy or greater to the primary tumor. Our primary endpoint is failure-free survival(FFS). Secondary end points include overall survival (OS), locoregional failure-free survival (LR-FFS), distant failure-free survival (D-FFS) rates and toxic effects. All efficacy analyses are conducted in the intention-to-treat population, and the safety population include only patients who receive their randomly assigned treatment.

• Study Type: Interventional
• Enrollment (Estimated): 476
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Shaojun Lin, MD; Phone Number: 13860603879; Email: linshaojun@yeah.net
• Study Contact Backup: Name: Qiaojuan Guo, MD; Phone Number: 15080013157; Email: guoqiaojuan@163.com

Study Locations

• China
  • Fujian
    • Fuzhou, Fujian, China, 350014
      • Department of radiation oncology, Fujian cancer hospital

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Patients with newly histologically confirmed non-keratinizing (according to WHO histologically type).
• Tumor staged as III-Iva(except T3N0M0) (according to the 8th AJCC edition).
• No evidence of distant metastasis (M0).
• Satisfactory performance status: Karnofsky scale (KPS) ≥ 70.
• Adequate marrow: leucocyte count ≥ 4000/μL, hemoglobin ≥ 90g/L and platelet count ≥ 100000/μL.
• Normal liver function test: Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) < 1.5×upper limit of normal (ULN) concomitant with alkaline phosphatase (ALP) ≤ 2.5×ULN, and bilirubin ≤ ULN.
• Adequate renal function: creatinine clearance ≥ 60 ml/min.
• Patients must be informed of the investigational nature of this study and give written informed consent.

Exclusion Criteria:

• WHO Type keratinizing squamous cell carcinoma or basaloid squamous cell carcinoma.
• Age > 65 or < 18.
• Treatment with palliative intent.
• Prior malignancy except adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer.
• Pregnancy or lactation (consider pregnancy test in women of child-bearing age and emphasize effective contraception during the treatment period).
• History of previous RT (except for non-melanomatous skin cancers outside intended RT treatment volume).
• Prior chemotherapy or surgery (except diagnostic) to primary tumor or nodes.
• Any severe intercurrent disease, which may bring unacceptable risk or affect the compliance of the trial, for example, unstable cardiac disease requiring treatment, renal disease, chronic hepatitis, diabetes with poor control (fasting plasma glucose > 1.5×ULN), and emotional disturbance.

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
Experimental: The immunotherapy and induction chemotherapy plus RT alone group; Patients receive Anti-PD-1 Antibody, gemcitabine (1000 mg/m² d1,8) and cisplatin (80mg/m² d1) every 3 weeks for three cycles before radiotherapy, and then receive intensity modulated-radiotherapy (IMRT) alone.	Drug: without concurrent cisplatin chemotherapy; IMRT without concurrent cisplatin chemotherapy
Active Comparator: The immunotherapy and induction chemotherapy plus CCRT group; Patients receive Anti-PD-1 Antibody, gemcitabine (1000 mg/m² d1,8) , cisplatin (80mg/m² d1) every 3 weeks for three cycles and cisplatin 80-100 mg/m² every 3 weeks for 2 cycles, concurrently with intensity-modulated radiotherapy (IMRT)	Drug: with concurrent cisplatin chemotherapy; IMRT with concurrent cisplatin chemotherapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Failure-free survival	Failure-free survival rate is calculated from the date of randomization to the date of treatment failure or death from any cause, whichever is first	3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival	Overall survival is calculated from randomization to death from any cause	3 years
Locoregional failure-free survival	Locoregional failure-free survival is calculated from randomization to the first locoregional failure	3 years
Distant failure-free survival	Distant failure-free survival is calculated from randomization to the first remote failure	3 years

Collaborators and Investigators

• Sponsor: Fujian Cancer Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): January 1, 2024
• Primary Completion (Estimated): January 1, 2025
• Study Completion (Estimated): January 1, 2028

Study Registration Dates

• First Submitted: October 18, 2023
• First Submitted That Met QC Criteria: October 18, 2023
• First Posted (Actual): October 23, 2023

Study Record Updates

• Last Update Posted (Actual): October 23, 2023
• Last Update Submitted That Met QC Criteria: October 18, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• 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; Antineoplastic Agents; Cisplatin
• Other Study ID Numbers: NPC010

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