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

Nasopharyngeal Carcinoma Clinical Trial

Official title:

A Multicenter Randomized Controlled Trial Comparing Reduced Dose With Regular Dose Intensity-modulated Radiotherapy for Chemotherapy Sensitive Stage II-III Nasopharyngeal Carcinoma

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04448522
• Other study ID #: SYSUCC-MYC-2020-1201
• Status: Recruiting
• Phase: Phase 3
• Start date: August 18, 2020
• Est. completion date: August 2028

Study information

• Verified date: September 2020
• Source: Sun Yat-sen University
• Contact: Ming-Yuan Chen, MD, PhD
• Phone: 86-20-87343624
• Email: chmingy[@]mail.sysu.edu.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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)

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 information / eligibility

• Status: Recruiting
• Enrollment: 508
• Est. completion date: August 2028
• Est. primary completion date: August 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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.

Related Conditions & MeSH terms

• Carcinoma
• Chemotherapy
• Nasopharyngeal Carcinoma
• Radiotherapy

Intervention

Radiation:
• reduced dosage IMRT
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. 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. IMRT: PTVnx:63.6Gy/30Fr/2.12Gy; PTVnd:63.6Gy/30Fr/2.12Gy; PTV1:54Gy/30Fr/1.8Gy; PTV2:49.2Gy/30Fr/1.64Gy
• conventional dosage IMRT
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. 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. IMRT: PTVnx:69.96Gy/33Fr/2.12Gy; PTVnd:69.96Gy/33Fr/2.12Gy; PTV1:59.4Gy/33Fr/1.8Gy; PTV2:54Gy/33Fr/1.64Gy

Locations

Country	Name	City	State
China	Cancer Center of Guangzhou Medical University	Guangzhou	Guangdong
China	Sun Yat-sen University Cancer Center	Guangzhou	Guangdong
China	Yuebei People's Hospital	Shaoguan	Guangdong
China	Wuzhou Red Cross Hospital	Wuzhou	Guangxi
China	Zhongshan People's Hospital	Zhongshan	Guangdong
Singapore	National Cancer Centre Singapore	Singapore

Sponsors (6)

Lead Sponsor	Collaborator
Sun Yat-sen University	Affiliated Cancer Hospital & Institute of Guangzhou Medical University, National Cancer Centre, Singapore, Wuzhou Red Cross Hospital, Yuebei People's Hospital, Zhongshan People's Hospital, Guangdong, China

Countries where clinical trial is conducted

China,  Singapore, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progress-free survival (PFS)	Defined as time from randomization to locoregional or distant metastasis relapse or death from any cause, whichever occurred first.	3 years
Secondary	Overall Survival (OS)	Defined as the time interval from randomization to death due to any cause.	3 years
Secondary	Distant Metastasis-Free Survival (DMFS)	Defined as the time interval from randomisation to the date of first distant metastases.	3 years
Secondary	Locoregional Relapse-Free Survival (LRRFS)	Defined as the time from randomisation to the date of first locoregional relapse.	3 years
Secondary	Incidence of treatment related acute complications	The proportion of patients with treatment related acute complications according to NCI-CTC5.0 criteria and RTOG criteria.	up to 1 years
Secondary	Incidence of treatment related late complications	The proportion of patients with treatment related late complications according to NCI-CTC5.0 criteria and RTOG criteria.	up to 3 years
Secondary	Score of survival quality according to the EORTC Quality of Life Questionnaire (QLQ)-C30 (V3.0)	Score of survival quality according to the EORTC Quality of Life Questionnaire (QLQ)-C30 (V3.0) before treatment, during treatment, after treatment.	up to 3 years
Secondary	Score of survival quality according to the EORTC Quality of Life Questionnaire Head and Neck (The QLQ-H&N35)	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.	up to 3 years