Phase III Trial of Concurrent Chemotherapy Alone in Patients With Low-risk Nasopharyngeal Carcinoma

Concurrent Chemoradiotherapy Alone Versus Induction Chemotherapy Plus Concurrent Chemoradiotherapy in Low-risk Locoregionally Advanced Nasopharyngeal Carcinoma: a Phase 3, Multicentre, Randomised Controlled Trial

The purpose of this study is to compare concurrent chemoradiotherapy (CCRT) alone with induction chemotherapy (gemcitabine+cisplatin) plus CCRT in patients with low-risk locoregionally advanced nasopharyngeal carcinoma(NPC).

Study Overview

• Status: Recruiting
• Conditions: Nasopharyngeal Carcinoma
• Intervention / Treatment: Radiation: IMRT and concurrent cisplatin; Drug: gemcitabine and cisplatin (Induction chemotherapy)

Detailed Description

Patients with low risk NPC( Stage III-IVa, except T4N2/AnyTN3, AJCC 8th and EBV DNA <4000 copies/ml) are randomly assigned to receive CCRT alone or induction chemotherapy plus CCRT. Patients in both groups receive cisplatin 100 mg/m² every 3 weeks for 3 cycles, concurrently with intensity-modulated radiotherapy (IMRT). IMRT is given as 2.12 Gy per fraction with five daily fractions per week to a total dose of 70 Gy. The induction chemotherapy plus CCRT group receive gemcitabine (1000 mg/m² d1,8) and cisplatin (80mg/m² d1) every 3 weeks for three cycles before CCRT. Our primary endpoint is progress-free survival. Secondary end points include overall survival (OS), Locoregional progression, Distant progression 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): 454
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Hai-Qiang Mai; Phone Number: 862087343643; Email: maihq@sysucc.org.cn

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China
      • Recruiting
      • Sun Yat-sen University Cancer Center
      • Contact: Hai-Qiang Mai
    • Guangzhou, Guangdong, China
      • Not yet recruiting
      • Guangzhou Panyu Central Hospital
      • Contact: Guo-Rong Zou, PhD
    • Zhongshan, Guangdong, China, 528499
      • Not yet recruiting
      • Zhongshan City People's Hospital
      • Contact: Feng Lei, MD; Phone Number: 13528227676
  • Guangxi
    • Nanning, Guangxi, China, 530021
      • Not yet recruiting
      • The First Affiliated Hospital of Guangxi Medical University
      • Contact: Ren-Sheng Wang, MD; Phone Number: 13807806008
  • Guizhou
    • Guiyang, Guizhou, China
      • Not yet recruiting
      • Cancer Hospital of Guizhou Province
      • Contact: Feng Jin, PhD
  • Hubei
    • Wuhan, Hubei, China
      • Not yet recruiting
      • Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology
      • Contact: Guang-Yuan Hu, PhD
    • Wuhan, Hubei, China
      • Not yet recruiting
      • Union Hospital, Tongji Medical College,Huazhong University of Science and Technology;
      • Contact: Kun-Yu Yang
  • Hunan
    • Changsha, Hunan, China
      • Not yet recruiting
      • Hunan Cancer Hospital
      • Contact: Huai Liu, PhD

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Age 18-70 years old.
2. Patients with newly histologically confirmed non-keratinizing (according to WHO histologically type).
3. Tumor staged as III-IVa except T4N2/AnyTN3 (according to the 8th AJCC edition) and pretreatment plasm EB Virus DNA<4000copies/ml.
4. ECOG Performance status less or equal to 1.
5. Male and no pregnant female.
6. Adequate marrow: leucocyte count ≥ 4000/μL, hemoglobin ≥ 90g/L and platelet count ≥ 100000/μL.
7. 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.
8. Adequate renal function: creatinine clearance ≥ 60 ml/min.
9. Patients must be informed of the investigational nature of this study and give written informed consent.

Exclusion Criteria:

1. Patients have evidence of relapse or distant metastasis.
2. WHO Type keratinizing squamous cell carcinoma or basaloid squamous cell carcinoma.
3. Treatment with palliative intent.
4. History of previous RT (except for non-melanomatous skin cancers outside intended RT treatment volume).
5. Prior chemotherapy or surgery (except diagnostic) to primary tumor or nodes.
6. Pregnancy or lactation (consider pregnancy test in women of child-bearing age and emphasize effective contraception during the treatment period).
7. Prior malignancy except adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer.
8. 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: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: IMRT and concurrent cisplatin; Patients receive intensity modulated-radiotherapy (IMRT), concurrently with cisplatin 100 mg/m² every 3 weeks for 3 cycles.	Radiation: IMRT and concurrent cisplatin; Patients receive concurrent cisplatin 100mg/m2 every 21days for three cycles during Intensity modulated radiotherapy (IMRT)
Active Comparator: Induction chemotherapy+IMRT and concurrent cisplatin; Patients receive gemcitabine (1000 mg/m² d1,8) and cisplatin (80mg/m² d1) every 3 weeks for 3 cycles before radiotherapy, and then receive intensity modulated-radiotherapy (IMRT), concurrently with cisplatin 100 mg/m² every 3 weeks for 3 cycles.	Radiation: IMRT and concurrent cisplatin; Patients receive concurrent cisplatin 100mg/m2 every 21days for three cycles during Intensity modulated radiotherapy (IMRT); Drug: gemcitabine and cisplatin (Induction chemotherapy); Patients receive gemcitabine (1000 mg/m² d1,8) and cisplatin (80mg/m² d1) every 3 weeks for 3 cycles before radiotherapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progress-free survival(PFS)	defined as the time from random assignment to documented local or regional relapse, distant metastasis, or death from any cause, whichever occurred first.	3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall response rate	Tumour response was classified according to RECIST, version 1.1	16 weeks after completion of concurrent chemoradiotherapy
Overall survival(OS)	defined as the time from random assignment to death from any cause.	3 years
Locoregional progression	defined as the time from random assignment to the occurrence of a locoregional progression. Cumulative incidence of locoregional progression will be calculated within a competing risk framework (Fine and Gray 1999).	3 years
Distant progression	defined as the time from random assignment to the occurrence of a distant progression. Cumulative incidence of distant progression will be calculated within a competing risk framework (Fine and Gray 1999).	3 years
Incidence of acute and late toxicity	Incidence of acute toxicity is calculated for each adverse event respectively and severity is evaluated on basis of Common Terminology Criteria for Adverse Events (CTCAE) 5.0 criteria. Late radiation toxicities were assessed using the Radiation Therapy Oncology Group and European Organization for Research and Treatment of Cancer late radiation morbidity scoring scheme.	3 years

Collaborators and Investigators

• Sponsor: Sun Yat-sen University
• Collaborators: Tongji Hospital; Hunan Cancer Hospital; Wuhan Union Hospital, China; Zhongshan People's Hospital, Guangdong, China; Guangzhou Panyu Central Hospital; First Affiliated Hospital of Guangxi Medical University; Cancer Hospital of Guizhou Province

Study record dates

Study Major Dates

• Study Start (Actual): September 7, 2023
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): September 1, 2029

Study Registration Dates

• First Submitted: July 30, 2023
• First Submitted That Met QC Criteria: July 30, 2023
• First Posted (Actual): August 7, 2023

Study Record Updates

• Last Update Posted (Actual): August 6, 2024
• Last Update Submitted That Met QC Criteria: August 2, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Keywords: Nasopharyngeal Carcinoma; Concurrent Chemotherapy; Induction Chemotherapy
• 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; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Cisplatin; Gemcitabine
• Other Study ID Numbers: 2022-FXY-298

Drug and device information, study documents

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