Chemotherapy, Nasopharyngeal Carcinoma, Radiotherapy
Conditions
Keywords
Nasopharyngeal carcinoma, intensity-modulated radiotherapy, chemotherapy
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.
Interventions
RADIATIONreduced dosage IMRT
1. Gemcitabine plus cisplatin induction chemotherapy: gemcitabine is injected intravenously at the dose of 1000 mg/m2 on the 1st and 8th day (within 30 minutes) for 3 cycles; cisplatin is injected intravenously at the dose of 80 mg/m2 on the 1st day, for 3 cycles. 1 cycles per 3 weeks. 2. Concurrent cisplatin chemotherapy: cisplatin is given at a dose of 100 mg/m2 via a continuous intravenous infusion during radiotherapy and starts on the 1st day of radiotherapy for 2 cycles. 1 cycles per 3 weeks. 3. IMRT: PTVnx：63.6Gy/30Fr/2.12Gy; PTVnd：63.6Gy/30Fr/2.12Gy; PTV1：54Gy/30Fr/1.8Gy; PTV2：49.2Gy/30Fr/1.64Gy
RADIATIONconventional dosage IMRT
1. Gemcitabine plus cisplatin induction chemotherapy: gemcitabine is injected intravenously at the dose of 1000 mg/m2 on the 1st and 8th day (within 30 minutes) for 3 cycles; cisplatin is injected intravenously at the dose of 80 mg/m2 on the 1st day, for 3 cycles. 1 cycles per 3 weeks. 2. Concurrent cisplatin chemotherapy: cisplatin is given at a dose of 100 mg/m2 via a continuous intravenous infusion during radiotherapy and starts on the 1st day of radiotherapy for 2 cycles. 1 cycles per 3 weeks. 3. IMRT: PTVnx：69.96Gy/33Fr/2.12Gy; PTVnd：69.96Gy/33Fr/2.12Gy; PTV1：59.4Gy/33Fr/1.8Gy; PTV2：54Gy/33Fr/1.64Gy
Sponsors
National Cancer Centre, Singapore
Affiliated Cancer Hospital & Institute of Guangzhou Medical University
Zhongshan People's Hospital, Guangdong, China
Yuebei People's Hospital
Wuzhou Red Cross Hospital
Sun Yat-sen University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 complications | up to 1 years | The proportion of patients with treatment related acute complications according to NCI-CTC5.0 criteria and RTOG criteria. |
| Overall Survival (OS) | 3 years | Defined as the time interval from randomization to death due to any cause. |
| 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. |
| 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. |
| Incidence of treatment related late complications | up to 3 years | The proportion of patients with treatment related late complications according to NCI-CTC5.0 criteria and RTOG criteria. |
Countries
China, Singapore
Contacts
Primary ContactMing-Yuan Chen, MD, PhD
Backup ContactRui You, MD, PhD
Outcome results
None listed