Clinical trial NCT04448522: Reduced vs Conventional Dosage Intensity-modulated Radiotherapy for Chemotherapy-sensitive Stage II-III Nasopharyngeal Carcinoma
Official title: A Multicenter Randomized Controlled Trial Comparing Reduced Dose With Regular Dose Intensity-modulated Radiotherapy for Chemotherapy Sensitive Stage II-III Nasopharyngeal Carcinoma
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Nasopharyngeal Carcinoma
Radiotherapy
Chemotherapy
Keywords: Nasopharyngeal carcinoma
intensity-modulated radiotherapy
chemotherapy
Lead sponsor: Sun Yat-sen University
Sponsor class: OTHER
Collaborators: name: National Cancer Centre, Singapore
name: Affiliated Cancer Hospital & Institute of Guangzhou Medical University
name: Zhongshan People's Hospital, Guangdong, China
name: Yuebei People's Hospital
name: Wuzhou Red Cross Hospital
First posted: 2020-06-26
Enrollment: 508
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Progress-free survival (PFS)
timeFrame: 3 years
Secondary outcomes:
measure: Overall Survival (OS)
timeFrame: 3 years
measure: Distant Metastasis-Free Survival (DMFS)
timeFrame: 3 years
measure: Locoregional Relapse-Free Survival (LRRFS)
timeFrame: 3 years
measure: Incidence of treatment related acute complications
timeFrame: up to 1 years
measure: Incidence of treatment related late complications
timeFrame: up to 3 years
measure: Score of survival quality according to the EORTC Quality of Life Questionnaire (QLQ)-C30 (V3.0)
timeFrame: up to 3 years
measure: Score of survival quality according to the EORTC Quality of Life Questionnaire Head and Neck (The QLQ-H&N35)
timeFrame: up to 3 years
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Sun Yat-sen University Cancer Center
state: Guangdong
city: Guangzhou
country: China
facility: Cancer Center of Guangzhou Medical University
state: Guangdong
city: Shaoguan
country: China
facility: Yuebei People's Hospital
state: Guangdong
city: Zhongshan
country: China
facility: Zhongshan People's Hospital
state: Guangdong
city: Wuzhou
country: China
facility: Wuzhou Red Cross Hospital
state: Guangxi
city: Singapore
country: Singapore
facility: National Cancer Centre Singapore
Study officials:
References: