Radiotherapy Alone Versus Concurrent Chemo-radiotherapy for Nasopharyngeal Carcincoma Patients With Undectable EBV DNA After One Cylce Neoadjuvant Chemotherpy

A Multicenter, Randomized, Non-inferior Phase III Study of Radiotherapy Alone Versus Concurrent Chemo-radiotherapy in Locally Advanced Nasopharyngeal Carcinoma Patients With Complete Remission of EBV DNA After One Cycle GP Regime Neoadjuvant Chemotherapy

The goal of this multicenter randomized non-inferior study is to compare radiotherapy alone versus concurrent chemoradiotherapy in locally advanced nasopharyngeal carcinoma patients whose EBV DNA drop to undetectable level after one cycle neoadjuvant chemotherapy using GP regimen. The main question it aims to answer is: the omission of concurrent chemotherapy is safe in the relatively good prognostic patients identified by the response of EBV DNA. Participants will be randomized to either radiotherapy alone or the standard treatment concurrent chemoradiotherapy if their EBV DNA decrease to undetectable level post first cycle of neoadjuvant chemotherapy and don't rebound in the second and third cycle.

Study Overview

• Status: Recruiting
• Conditions: Nasopharyngeal Carcinoma
• Intervention / Treatment: Drug: Radiotherapy; Drug: Cisplatin

• Study Type: Interventional
• Enrollment (Anticipated): 366
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Chengrun Du, MD and PhD; Phone Number: +86-15001733593; Email: duchengrun@qq.com

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200032
      • Recruiting
      • Fudan Universtiy Shanghai Cancer Centre
      • Contact: Hongmei Ying, M.D.; Phone Number: 81400 +8621-64175590; Email: yinghongmei2011@sina.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patients with newly histologically confirmed non-keratinizing nasopharyngeal carcinoma, type of WHO II or III.
2. Age 18-70 years.
3. Clinical stage III-IVa (based on the 8th American Joint Committee on Cancer[AJCC] edition).
4. Patients with detectable pre-treatment plasma EBV DNA but undetectable EBV DNA after one cycle neoadjuvant and no EBV DNA rebound during the second and third cycle.
5. ECOG (Eastern Cooperative Oncology Group) score: 0-1
6. Hemoglobin (HGB) ≥90 g/L, white blood cell (WBC) ≥4×109 /L, platelet (PLT) ≥100×109 /L.
7. Liver function: Alanine transaminase(ALT), Aspartate aminotransferase(AST)< 1.5 times the upper limit of normal value (ULN), total bilirubin <1.0×ULN.
8. Renal function: serum creatinine <1×ULN.
9. Patients must sign informed consent and be willing and able to comply with the requirements of visits, treatment, laboratory tests and other research requirements stipulated in the research schedule.

Exclusion Criteria:

1. Histologically confirmed keratinizing squamous cell carcinoma (WHO I)
2. Suffered from other malignant tumors (except the cure of basal cell carcinoma or uterine cervical carcinoma in situ) previously.
3. Receiving radiotherapy or chemotherapy or targeted therapy previously
4. Women of child-bearing potential who are pregnant or breastfeeding because of the potentially dangerous effects of the preparative chemotherapy on the fetus or infant.
5. Patients with significantly lower heart, liver, lung, kidney and bone marrow function.
6. Severe, uncontrolled medical conditions and infections.
7. At the same time using other test drugs or in other clinical trials.
8. Refusal or inability to sign informed consent to participate in the trial.
9. Emotional disturbance or mental illness, no civil capacity or limited capacity for civil conduct

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Radiotherapy alone; Patients with undectable plazma EBV DNA after first cycle neoadjuvant chemotherapy using GP regimen (gemcitabine 1000mg/m2 d1,8+ cisplatin 25mg/m2 d1-3) and without rebound during the course of second and third cycle received definitive radiotherapy to head and neck region.	Drug: Radiotherapy; IMRT for primary and regional field
Active Comparator: Concurrent chemoradiotherapy; Patients with undectable plazma EBV DNA after first cycle neoadjuvant chemotherapy using GP regimen (gemcitabine 1000mg/m2 d1,8+ cisplatin 25mg/m2 d1-3) and without rebound during the course of second and third cycle received definitive radiotherapy to head and neck region plus two cycles of concurent chemotherapy （cisplatin 80mg/m2）	Drug: Radiotherapy; IMRT for primary and regional field; Drug: Cisplatin; Cisplatin 80mg/m2, 21days/cycle, 2 cycles

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival	Defined from date of randomization to date of first documentation of progression or death due to any cause	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival	Defined from date of randomization to date of first documentation of death from any cause or censored at the date of the last follow-up.	2 years
Toxicities	Analysis of acute and late adverse events (AEs) are evaluated. Numbers of patients of treatment-related adverse events(acute toxicity) as assessed by CTCAE v5.0.Numbers of patients of 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.	2 years
change of quality of life	QoL scores were assessed for each scale by using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTCQLQ-C30) before induction chemotherapy, before radiotherapy, at the end of radiotherapy, at 3 months after radiotherapy, at 6 months after radiotherapy and 12 months after radiotherapy	1 year

Collaborators and Investigators

• Sponsor: Fudan University

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2022
• Primary Completion (Anticipated): January 1, 2025
• Study Completion (Anticipated): January 1, 2027

Study Registration Dates

• First Submitted: December 30, 2022
• First Submitted That Met QC Criteria: December 30, 2022
• First Posted (Actual): January 6, 2023

Study Record Updates

• Last Update Posted (Estimate): January 10, 2023
• Last Update Submitted That Met QC Criteria: January 7, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Head and Neck Neoplasms; Nasopharyngeal Diseases; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases; Nasopharyngeal Neoplasms; Carcinoma; Nasopharyngeal Carcinoma; Antineoplastic Agents; Cisplatin
• Other Study ID Numbers: 20122229-15

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No