Sequential or Concurrent Chemoradiotherapy in Patients With Locoregionally Advanced NPC

Non-inferiority Prospective Randomized Trial Comparing Sequential Chemoradiotherapy With Concurrent Chemoradiotherapy in Patients With Locoregionally Advanced Nasopharyngeal Carcinoma

The purpose of this study is to compare the efficacy and safety of sequential chemoradiotherapy (induction chemotherapy + intensity-modulated radiotherapy +adjuvant chemotherapy) with induction chemotherapy plus concurrent chemoradiotherapy in patients with locoregionally advanced nasopharyngeal carcinoma (NPC), in order to confirm the value of sequential chemoradiotherapy in NPC patients.

Study Overview

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

Detailed Description

Patients with non-keratinizing NPC III-IVA (UICC/AJCC 8th edition) are randomly assigned to receive sequential chemoradiotherapy (induction chemotherapy + intensity-modulated radiotherapy + adjuvant chemotherapy) or induction chemotherapy plus concurrent chemoradiotherapy. Intensity-modulated radiotherapy (IMRT) is given as 2.2 Gy per fraction with five daily fractions per week for 6-7 weeks to a total dose of 66 or 70.4 Gy to the primary tumor. The induction or adjuvant chemotherapy is given gemcitabine (1000 mg/m² d1,8) and cisplatin (25mg/m² d1-3) every 3 weeks for two cycles. The concurrent chemotherapy is given cisplatin 30 mg/m² every week concurrently with IMRT. Our primary endpoint is failure-free survival(FFS) and grade III mucositis during radiation. 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 (Anticipated): 420
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Chaosu Hu, MD,PhD; Phone Number: +86 18017312302; Email: hucsu62@yahoo.com
• Study Contact Backup: Name: Xiayun He, MD; Phone Number: +86 18017312167; Email: hexiayun1962@163.com

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200032
      • Recruiting
      • Fudan University Shanghai Cancer Center
      • Contact: Chaosu Hu, MD,PhD; Phone Number: +86 18017312302

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 61 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients with newly histologically confirmed non-keratinizing (according to WHO histologically type)
• Tumor staged as III-IVA (according to the 8th AJCC edition).
• Satisfactory performance status: Karnofsky scale (KPS) ≥ 70.
• Age between 18 and 65 years old.
• Adequate marrow: Neutrophil count ≥2000/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 ≤ 1.5ULN.
• 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:

• Evidence of distant metastasis
• Prior chemotherapy, radiotherapy or surgery (except diagnostic) to primary tumor or nodes.
• Other previous or concomitant cancer.
• Pregnancy or lactation.
• Presence of an uncontrolled concomitant illness including, but not limited to, ongoing or active infection, immune deficiency, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia or 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: Induction chemotherapy+IMRT+adjuvant chemotherapy; Patients receive gemcitabine (1000 mg/m² d1,8) and cisplatin (25 mg/m² d1-3) every 3 weeks for 2 cycles before radiotherapy, and then receive intensity modulated-radiotherapy (IMRT), followed by gemcitabine (1000 mg/m² d1,8) and cisplatin (25 mg/m² d1-3) every 3 weeks for 2 cycles.	Drug: gemcitabine and cisplatin (Induction and adjuvant chemotherapy); Patients receive gemcitabine (1000 mg/m² d1,8) and cisplatin (25mg/m² d1-3) every 3 weeks for 2 cycles before IMRT and after IMRT.; Radiation: IMRT; Intensity modulated-radiotherapy (IMRT) is given as 2.2 Gy per fraction with five daily fractions per week for 6-7 weeks to a total dose of 66 or 70.4 Gy to the primary tumor
Active Comparator: Induction chemotherapy+IMRT and concurrent cisplatin; Patients receive gemcitabine (1000 mg/m² d1,8) and cisplatin (25 mg/m² d1-3) every 3 weeks for 2 cycles before radiotherapy, and then receive intensity modulated-radiotherapy (IMRT), concurrently with cisplatin 30 mg/m² every week.	Drug: gemcitabine and cisplatin (Induction chemotherapy); Patients receive gemcitabine (1000 mg/m² d1,8) and cisplatin (25mg/m² d1-3) every 3 weeks for 2 cycles before concurrent chemoradiotherapy.; Radiation: IMRT and concurrent cisplatin; Intensity modulated-radiotherapy (IMRT) is given as 2.2 Gy per fraction with five daily fractions per week for 6-7 weeks to a total dose of 66 or 70.4Gy to the primary tumor, concurrently with cisplatin 30mg/m² every week.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Failure-free survival	Failure-free survival is calculated from the date of randomisation to the date of treatment failure or death from any cause, whichever is first.	3-year
Grade III or more mucositis	Grade III or more mucositis during radiotherapy	From the start of radiotherapy to 30 days after radiotherapy

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival	Overall survival is calculated from randomization to death from any cause.	3-year
Locoregional failure-free survival	Locoregional failure-free survival is calculated from randomization to the first locoregional failure.	3-year
Distant failure-free survival	Distant failure-free survival is calculated from randomization to the first remote failure.	3-year
Short-term treatment response	Treatment response after induction chemotherapy, IMRT and completion of treatment.	Two weeks after completion of induction chemotherapy. Three months after completion of the radiotherapy.
Number of participants with adverse events	Incidence of acute and late toxicity	up to 3 years
Quality of Life	Use EORTC QLQ-HN35.	up to 3 years

Collaborators and Investigators

• Sponsor: Chaosu Hu
• Collaborators: Zhejiang Cancer Hospital; Fujian Cancer Hospital; Affiliated Hospital of Jiangnan University; Jiangxi Provincial Cancer Hospital; First Affiliated Hospital of Wenzhou Medical University

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2018
• Primary Completion (Anticipated): September 30, 2024
• Study Completion (Anticipated): December 30, 2024

Study Registration Dates

• First Submitted: December 2, 2017
• First Submitted That Met QC Criteria: December 4, 2017
• First Posted (Actual): December 8, 2017

Study Record Updates

• Last Update Posted (Actual): March 4, 2022
• Last Update Submitted That Met QC Criteria: February 16, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Keywords: Nasopharyngeal Carcinoma; concurrent chemoradiotherapy; sequential chemoradiotherapy
• 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; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Gemcitabine; Cisplatin
• Other Study ID Numbers: GP2017-02（SANDWICH）

Drug and device information, study documents

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