Sequential or Concurrent Chemoradiotherapy in Patients With Locoregionally Advanced NPC

Nasopharyngeal Carcinoma Clinical Trial

Official title:

Non-inferiority Prospective Randomized Trial Comparing Sequential Chemoradiotherapy With Concurrent Chemoradiotherapy in Patients With Locoregionally Advanced Nasopharyngeal Carcinoma

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03366415
• Other study ID #: GP2017-02(SANDWICH)
• Status: Recruiting
• Phase: Phase 3
• Start date: January 1, 2018
• Est. completion date: December 30, 2024

Study information

• Verified date: February 2022
• Source: Fudan University
• Contact: Chaosu Hu, MD,PhD
• Phone: +86 18017312302
• Email: hucsu62[@]yahoo.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Recruiting
• Enrollment: 420
• Est. completion date: December 30, 2024
• Est. primary completion date: September 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Carcinoma
• Nasopharyngeal Carcinoma

Intervention

Drug:
• gemcitabine and cisplatin (Induction and adjuvant chemotherapy)
Patients receive gemcitabine (1000 mg/m² d1,8) and cisplatin (25mg/m² d1-3) every 3 weeks for 2 cycles before IMRT and after IMRT.

Radiation:
• IMRT
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

Drug:
• gemcitabine and cisplatin (Induction chemotherapy)
Patients receive gemcitabine (1000 mg/m² d1,8) and cisplatin (25mg/m² d1-3) every 3 weeks for 2 cycles before concurrent chemoradiotherapy.

Radiation:
• IMRT and concurrent cisplatin
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 70.4Gy to the primary tumor, concurrently with cisplatin 30mg/m² every week.

Locations

Country	Name	City	State
China	Fudan University Shanghai Cancer Center	Shanghai	Shanghai

Sponsors (6)

Lead Sponsor	Collaborator
Chaosu Hu	Affiliated Hospital of Jiangnan University, First Affiliated Hospital of Wenzhou Medical University, Fujian Cancer Hospital, Jiangxi Provincial Cancer Hospital, Zhejiang Cancer Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Failure-free survival	Failure-free survival is calculated from the date of randomisation to the date of treatment failure or death from any cause, whichever is first.	3-year
Primary	Grade III or more mucositis	Grade III or more mucositis during radiotherapy	From the start of radiotherapy to 30 days after radiotherapy
Secondary	Overall survival	Overall survival is calculated from randomization to death from any cause.	3-year
Secondary	Locoregional failure-free survival	Locoregional failure-free survival is calculated from randomization to the first locoregional failure.	3-year
Secondary	Distant failure-free survival	Distant failure-free survival is calculated from randomization to the first remote failure.	3-year
Secondary	Short-term treatment response	Treatment response after induction chemotherapy, IMRT and completion of treatment.	Two weeks after completion of induction chemotherapy. Three months after completion of the radiotherapy.
Secondary	Number of participants with adverse events	Incidence of acute and late toxicity	up to 3 years
Secondary	Quality of Life	Use EORTC QLQ-HN35.	up to 3 years