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Sequential or Concurrent Chemoradiotherapy in Patients With Locoregionally Advanced NPC

Phase 3
Recruiting
Conditions
Nasopharyngeal Carcinoma
Interventions
Registration Number
NCT03366415
Lead Sponsor
Chaosu Hu
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.

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.

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
420
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 & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Induction chemotherapy+IMRT+adjuvant chemotherapygemcitabine and cisplatin (Induction and 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.
Induction chemotherapy+IMRT+adjuvant chemotherapyIMRTPatients 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.
Induction chemotherapy+IMRT and concurrent cisplatingemcitabine and cisplatin (Induction 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), concurrently with cisplatin 30 mg/m² every week.
Induction chemotherapy+IMRT and concurrent cisplatinIMRT and concurrent cisplatinPatients 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.
Primary Outcome Measures
NameTimeMethod
Failure-free survival3-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 mucositisFrom the start of radiotherapy to 30 days after radiotherapy

Grade III or more mucositis during radiotherapy

Secondary Outcome Measures
NameTimeMethod
Overall survival3-year

Overall survival is calculated from randomization to death from any cause.

Distant failure-free survival3-year

Distant failure-free survival is calculated from randomization to the first remote failure.

Locoregional failure-free survival3-year

Locoregional failure-free survival is calculated from randomization to the first locoregional failure.

Short-term treatment responseTwo 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 eventsup to 3 years

Incidence of acute and late toxicity

Quality of Lifeup to 3 years

Use EORTC QLQ-HN35.

Trial Locations

Locations (1)

Fudan University Shanghai Cancer Center

🇨🇳

Shanghai, Shanghai, China

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