Phase III Trial of Concurrent Chemotherapy Alone in Patients With Low-risk Nasopharyngeal Carcinoma

Sponsor

Sun Yat-sen University (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05979961

Collaborator

(none)

424

Enrollment

Locations

Arms

Anticipated Duration (Months)

106

Patients Per Site

2.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to compare concurrent chemoradiotherapy (CCRT) alone with induction chemotherapy (gemcitabine+cisplatin) plus CCRT in patients with low-risk locoregionally advanced nasopharyngeal carcinoma(NPC).

Condition or Disease	Intervention/Treatment	Phase
Nasopharyngeal Carcinoma	Radiation: IMRT and concurrent cisplatin Drug: gemcitabine and cisplatin (Induction chemotherapy)	Phase 3

Detailed Description

Patients with low risk NPC( Stage III-IVa, except T4N2/AnyTN3, AJCC 8th and EBV DNA <4000 copies/ml) are randomly assigned to receive CCRT alone or induction chemotherapy plus CCRT. Patients in both groups receive cisplatin 100 mg/m² every 3 weeks for 3 cycles, concurrently with intensity-modulated radiotherapy (IMRT). IMRT is given as 2.12 Gy per fraction with five daily fractions per week to a total dose of 70 Gy. The induction chemotherapy plus CCRT group receive gemcitabine (1000 mg/m² d1,8) and cisplatin (80mg/m² d1) every 3 weeks for three cycles before CCRT. Our primary endpoint is progress-free survival. Secondary end points include overall survival (OS), Locoregional progression, Distant progression 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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

424 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Concurrent Chemoradiotherapy Alone Versus Induction Chemotherapy Plus Concurrent Chemoradiotherapy in Low-risk Locoregionally Advanced Nasopharyngeal Carcinoma: a Phase 3, Multicentre, Randomised Controlled Trial

Anticipated Study Start Date :

Aug 1, 2023

Anticipated Primary Completion Date :

Jul 1, 2025

Anticipated Study Completion Date :

Jul 1, 2027

Arms and Interventions

Arm	Intervention/Treatment
Experimental: IMRT and concurrent cisplatin Patients receive intensity modulated-radiotherapy (IMRT), concurrently with cisplatin 100 mg/m² every 3 weeks for 3 cycles.	Radiation: IMRT and concurrent cisplatin Patients receive concurrent cisplatin 100mg/m2 every 21days for three cycles during Intensity modulated radiotherapy (IMRT)
Active Comparator: Induction chemotherapy+IMRT and concurrent cisplatin Patients receive gemcitabine (1000 mg/m² d1,8) and cisplatin (80mg/m² d1) every 3 weeks for 3 cycles before radiotherapy, and then receive intensity modulated-radiotherapy (IMRT), concurrently with cisplatin 100 mg/m² every 3 weeks for 3 cycles.	Radiation: IMRT and concurrent cisplatin Patients receive concurrent cisplatin 100mg/m2 every 21days for three cycles during Intensity modulated radiotherapy (IMRT) Drug: gemcitabine and cisplatin (Induction chemotherapy) Patients receive gemcitabine (1000 mg/m² d1,8) and cisplatin (80mg/m² d1) every 3 weeks for 3 cycles before radiotherapy

Arm

Intervention/Treatment

Experimental: IMRT and concurrent cisplatin

Patients receive intensity modulated-radiotherapy (IMRT), concurrently with cisplatin 100 mg/m² every 3 weeks for 3 cycles.

Radiation: IMRT and concurrent cisplatin

Patients receive concurrent cisplatin 100mg/m2 every 21days for three cycles during Intensity modulated radiotherapy (IMRT)

Active Comparator: Induction chemotherapy+IMRT and concurrent cisplatin

Patients receive gemcitabine (1000 mg/m² d1,8) and cisplatin (80mg/m² d1) every 3 weeks for 3 cycles before radiotherapy, and then receive intensity modulated-radiotherapy (IMRT), concurrently with cisplatin 100 mg/m² every 3 weeks for 3 cycles.

Radiation: IMRT and concurrent cisplatin

Patients receive concurrent cisplatin 100mg/m2 every 21days for three cycles during Intensity modulated radiotherapy (IMRT)

Drug: gemcitabine and cisplatin (Induction chemotherapy)

Patients receive gemcitabine (1000 mg/m² d1,8) and cisplatin (80mg/m² d1) every 3 weeks for 3 cycles before radiotherapy

Outcome Measures

Primary Outcome Measures

Progress-free survival(PFS) [2 years]
defined as the time from random assignment to documented local or regional relapse, distant metastasis, or death from any cause, whichever occurred first.

Secondary Outcome Measures

Overall survival(OS) [2 years]
defined as the time from random assignment to death from any cause.
Locoregional progression [2 years]
defined as the time from random assignment to the occurrence of a locoregional progression. Cumulative incidence of locoregional progression will be calculated within a competing risk framework (Fine and Gray 1999).
Distant progression [2 years]
defined as the time from random assignment to the occurrence of a distant progression. Cumulative incidence of distant progression will be calculated within a competing risk framework (Fine and Gray 1999).
Overall response rate [16 weeks after completion of concurrent chemoradiotherapy]
Tumour response was classified according to RECIST, version 1.1
Incidence of acute and late toxicity [2 years]
Incidence of acute toxicity is calculated for each adverse event respectively and severity is evaluated on basis of Common Terminology Criteria for Adverse Events (CTCAE) 5.0 criteria. Late radiation toxicities were assessed using the Radiation Therapy Oncology Group and European Organization for Research and Treatment of Cancer late radiation morbidity scoring scheme.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Age 18-70 years old.
Patients with newly histologically confirmed non-keratinizing (according to WHO histologically type).
Tumor staged as III-IVa except T4N2/AnyTN3 (according to the 8th AJCC edition) and pretreatment plasm EB Virus DNA<4000copies/ml.
ECOG Performance status less or equal to 1.
Male and no pregnant female.
Adequate marrow: leucocyte count ≥ 4000/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 < ULN.
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:

Patients have evidence of relapse or distant metastasis.
WHO Type keratinizing squamous cell carcinoma or basaloid squamous cell carcinoma.
Treatment with palliative intent.
History of previous RT (except for non-melanomatous skin cancers outside intended RT treatment volume).
Prior chemotherapy or surgery (except diagnostic) to primary tumor or nodes.
Pregnancy or lactation (consider pregnancy test in women of child-bearing age and emphasize effective contraception during the treatment period).
Prior malignancy except adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer.
Any severe intercurrent disease, which may bring unacceptable risk or affect the compliance of the trial, for example, unstable cardiac disease requiring treatment, renal disease, chronic hepatitis, diabetes with poor control (fasting plasma glucose > 1.5×ULN), and emotional disturbance.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Guangzhou Medical University	Guangzhou	Guangdong	China	510000
2	The First Affiliated Hospital of Sun Yat-sen University	Guangzhou	Guangdong	China	510062
3	Zhongshan City People's Hospital	Zhongshan	Guangdong	China	528499
4	The First Affiliated Hospital of Guangxi Medical University	Nanning	Guangxi	China	530021