Sequential or Concurrent Chemoradiotherapy in Patients With Locoregionally Advanced NPC

Sponsor

Chaosu Hu (Other)

Overall Status

Recruiting

CT.gov ID

NCT03366415

Collaborator

Zhejiang Cancer Hospital (Other), Jiangxi Provincial Cancer Hospital (Other), First Affiliated Hospital of Wenzhou Medical University (Other), Affiliated Hospital of Jiangnan University (Other), Fujian Cancer Hospital (Other)

420

Enrollment

Location

Arms

83.9

Anticipated Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Nasopharyngeal Carcinoma	Drug: gemcitabine and cisplatin (Induction and adjuvant chemotherapy) Radiation: IMRT Drug: gemcitabine and cisplatin (Induction chemotherapy) Radiation: IMRT and concurrent cisplatin	Phase 3

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 Design

Study Type:

Interventional

Anticipated Enrollment :

420 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Stratified by stageStratified by stage

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Jan 1, 2018

Anticipated Primary Completion Date :

Sep 30, 2024

Anticipated Study Completion Date :

Dec 30, 2024

Arms and Interventions

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.

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

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.

Outcome Measures

Primary Outcome Measures

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

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.