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Reduced vs Conventional Dosage Intensity-modulated Radiotherapy for Chemotherapy-sensitive Stage II-III Nasopharyngeal Carcinoma

Phase 3
Recruiting
Conditions
Chemotherapy
Radiotherapy
Nasopharyngeal Carcinoma
Interventions
Radiation: reduced dosage IMRT
Radiation: conventional dosage IMRT
Registration Number
NCT04448522
Lead Sponsor
Sun Yat-sen University
Brief Summary

Through multicenter, open-label, randomised clinical trials, we intend to demonstrate that radiotherapy with reduced dose could significantly reduce the incidence of radiotherapy toxicities, improve the quality of life of patients while ensuring the tumor control rates for NPC patients staged as II-III who are sensitive to induction chemotherapy (imaging evaluation of CR/PR and EBV DNA copy number decreased to 0 copies/mL after induction chemotherapy)

Detailed Description

Through multicenter, open-label, randomised clinical trials, patients with NPC staged as II-III with CR/PR according to RECIST criteria and EBV DNA decreased to 0 copies/mL after 3 cycles of GP induction chemotherapy will be randomized into experimental group to receive IMRT of reduced dose (prescribed dose, 63.6 Gy, 2.12 Gy per fractions, 30 fractions) and control group to receive IMRT of conventional dose (prescribed dose, 69.96 Gy, 2.13 Gy per time, 33 fractions). Two cycles of cisplatin chemotherapy will be performed during IMRT. The efficacy, toxicity, and quality of life of patients between the two groups will be compared.

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
508
Inclusion Criteria
  1. Histologically confirmed non-keratinizing nasopharyngeal carcinoma (differentiated or undifferentiated type, i.e., WHO type II or type III).

  2. Staged as T1-3N1-2M0, T2-3N0M0 (stage II-III) at diagnosis (according to the 8th AJCC edition).

  3. Aged between 18-70 years.

  4. Karnofsky scale (KPS)≥70.

  5. Normal bone marrow function.

  6. Evaluated as PR or CR after 3 cycles of GP induction chemotherapy.

  7. EBV DNA copy number decreased to 0 copies/mL after 3 cycles of GP induction chemotherapy.

  8. Normal liver and kidney function:

    1. total bilirubin, AST and ALT levels of no more than 2.5 times the upper normal limit;
    2. creatinine clearance rate of at least 60 mL/min or creatinine of no more than 1.5 times the upper normal limit.
  9. Given written informed consent.

Exclusion Criteria
  1. Histologically confirmed keratinized squamous cell carcinoma (WHO type I) or basal squamous cell carcinoma.
  2. Recurrent or metastatic nasopharyngeal carcinoma.
  3. Evaluated as SD or PD after 3 cycles of GP induction chemotherapy.
  4. EBV DNA copy number of more than 0 copies/mL after 3 cycles of GP induction chemotherapy.
  5. Pregnancy or lactation (Pregnancy tests should be considered for women in childbearing age, and effective contraception should be emphasized during treatment.)
  6. Other invasive malignant diseases in the past, other than cured basal cell skin carcinoma, squamous cell carcinoma, cervical carcinoma in situ.
  7. Primary and regional lesions have been treated with chemotherapy or surgery (except diagnostic purpose)
  8. Any severe disease, which may cause unacceptable risk factors or affect compliance with the trial, for example, unstable heart disease requiring treatment, kidney disease, chronic hepatitis, poorly controlled diabetes (fasting blood glucose > 1.5×ULN), and mental illness.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Reduced dosage IMRT groupreduced dosage IMRT3 cycles of gemcitabin and cisplatin induction chemotherapy plus concurrent cheomtherapy with IMRT dosage of 63.6 Gy
Conventional dosage IMRT groupconventional dosage IMRT3 cycles of gemcitabin and cisplatin induction chemotherapy plus concurrent cheomtherapy with IMRT dosage of 69.96 Gy
Primary Outcome Measures
NameTimeMethod
Progress-free survival (PFS)3 years

Defined as time from randomization to locoregional or distant metastasis relapse or death from any cause, whichever occurred first.

Secondary Outcome Measures
NameTimeMethod
Overall Survival (OS)3 years

Defined as the time interval from randomization to death due to any cause.

Distant Metastasis-Free Survival (DMFS)3 years

Defined as the time interval from randomisation to the date of first distant metastases.

Locoregional Relapse-Free Survival (LRRFS)3 years

Defined as the time from randomisation to the date of first locoregional relapse.

Incidence of treatment related acute complicationsup to 1 years

The proportion of patients with treatment related acute complications according to NCI-CTC5.0 criteria and RTOG criteria.

Score of survival quality according to the EORTC Quality of Life Questionnaire Head and Neck (The QLQ-H&N35)up to 3 years

Score of survival quality according to the EORTC Quality of Life Questionnaire Head and Neck (The QLQ-H\&N35) before treatment, during treatment, after treatment.

Score of survival quality according to the EORTC Quality of Life Questionnaire (QLQ)-C30 (V3.0)up to 3 years

Score of survival quality according to the EORTC Quality of Life Questionnaire (QLQ)-C30 (V3.0) before treatment, during treatment, after treatment.

Incidence of treatment related late complicationsup to 3 years

The proportion of patients with treatment related late complications according to NCI-CTC5.0 criteria and RTOG criteria.

Trial Locations

Locations (6)

Yuebei People's Hospital

🇨🇳

Shaoguan, Guangdong, China

Zhongshan People's Hospital

🇨🇳

Zhongshan, Guangdong, China

Sun Yat-sen University Cancer Center

🇨🇳

Guangzhou, Guangdong, China

Wuzhou Red Cross Hospital

🇨🇳

Wuzhou, Guangxi, China

Cancer Center of Guangzhou Medical University

🇨🇳

Guangzhou, Guangdong, China

National Cancer Centre Singapore

🇸🇬

Singapore, Singapore

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