GP vs PF as Induction Chemotherapy Combined With CCRT for Locoregionally Advanced Nasopharyngeal Carcinoma

• ClinicalTrials.gov Identifier: NCT03840421
• Recruitment Status: Recruiting
• First Posted: February 15, 2019
• Last Update Posted: October 22, 2020
• Sponsor: Sun Yat-sen University
• Collaborators: Affiliated Cancer Hospital & Institute of Guangzhou Medical University; Guangdong Provincial People's Hospital; First Affiliated Hospital, Sun Yat-Sen University
• Information provided by (Responsible Party): Ming-Yuan Chen, Sun Yat-sen University

Study Description

Brief Summary:

The purpose of this study is to compare the survival and toxicity of GP (gemcitabine and cisplatin) vs. PF (cisplatin and fluorouracil) as induction chemotherapy combined with concurrent chemoradiotherapy (CCRT) for locoregionally advanced nasopharyngeal carcinoma( NPC ) patients.

Condition or disease	Intervention/treatment	Phase
Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms; Nasopharyngeal Diseases; Head and Neck Neoplasm	Drug: gemcitabine and cisplatin; Drug: cisplatin and fluorouracil; Radiation: IMRT; Drug: cisplatin	Phase 3

Detailed Description:

Patients presented with non-keratinizing NPC and stage T1-4N2-3/T4N0-1M0 are randomly assigned to receive GP (gemcitabine and cisplatin) or PF (cisplatin and fluorouracil) induction chemotherapy combined with concurrent chemoradiotherapy. Patients in both arms receive radical radiotherapy, and cisplatin (100mg/m²) every three weeks for two cycles during radiotherapy. Patients in the investigational arm receive gemcitabine (1000 mg/m² d1,8) and cisplatin (80mg/m² d1) every 3 weeks for three cycles. Patients in the control arm receive fluorouracil (800mg/m² d1-5) and cisplatin (80mg/m² d1) every 3 weeks for three cycles. Our primary endpoint is progress-free survival (PFS). Secondary end points include distant metastasis-free survival (DMFS), overall survival (OS), locoregional relapse-free survival (LRRFS), initial response rates after treatments, toxic effects and quality of life (QoL).

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 468 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: GP vs PF as Induction Chemotherapy Combined With CCRT for Locoregionally Advanced Nasopharyngeal Carcinoma：a Prospective,Parallel, Randomized, Open Labeled, Multicenter Phase III Clinical Trial
• Actual Study Start Date: April 3, 2019
• Estimated Primary Completion Date: February 14, 2023
• Estimated Study Completion Date: February 14, 2026

Arms and Interventions

Arm	Intervention/treatment
Experimental: gemcitabine and 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 2 cycles.	Drug: gemcitabine and cisplatin; Patients receive gemcitabine (1000 mg/m² d1,8) and cisplatin (80mg/m² d1) every 3 weeks for 3 cycles before concurrent chemoradiotherapy.; Other Name: gemcitabine and cisplatin (GP); Radiation: IMRT; Intensity modulated-radiotherapy (IMRT) is given as 30～33 fraction with five daily fractions per week for 6-7 weeks to a total dose of 68～70 Gy to the primary tumor; Drug: cisplatin; IMRT concurrently with cisplatin 100 mg/m² every 3 weeks for 2 cycles.; Other Name: cisplatin（DDP）
Active Comparator: cisplatin and fluorouracil; Patients receive fluorouracil (800mg/m² d1-5) 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 2 cycles.	Drug: cisplatin and fluorouracil; Patients receive fluorouracil (800mg/m2 d1-5) and cisplatin (80mg/m² d1) every 3 weeks for 3 cycles before concurrent chemoradiotherapy.; Other Name: cisplatin and fluorouracil (PF); Radiation: IMRT; Intensity modulated-radiotherapy (IMRT) is given as 30～33 fraction with five daily fractions per week for 6-7 weeks to a total dose of 68～70 Gy to the primary tumor; Drug: cisplatin; IMRT concurrently with cisplatin 100 mg/m² every 3 weeks for 2 cycles.; Other Name: cisplatin（DDP）

Outcome Measures

Primary Outcome Measures :

1. progress-free survival (PFS) [ Time Frame: 3 years ]
   Progress-free survival is calculated from the date of randomization to the date of the first progress at any site.

Secondary Outcome Measures :

1. Distant Metastasis-Free Survival (DMFS) [ Time Frame: 3 years ]
   The DMFS is evaluated and calculated from the date of random assignment until the day of first distant metastases or until the date of the last follow-up visit.
2. Overall Survival (OS) [ Time Frame: 3 years ]
   The OS was defined as the duration from the date of random assignment to the date of death from any cause or censored at the date of the last follow-up.
3. Locoregional Relapse-Free Survival (LRRFS) [ Time Frame: 3 years ]
   The LRRFS is evaluated and calculated from the date of random assignment until the day of first locoregional relapse or until the date of the last follow-up visit.
4. Number of participants with adverse events [ Time Frame: up to 3 years ]
   Incidence of acute and late toxicity

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Patients with newly histologically confirmed non-keratinizing nasopharyngeal carcinoma, including WHO II or III
• Tumor staged as T1-4N2-3/T4N0-1M0（according to the 8th AJCC edition）
• Male and no pregnant female
• Age between 18-65
• Adequate marrow: leucocyte count ≥4000/μL, hemoglobin ≥90g/L and platelet count ≥100000/μL
• Normal liver function test: Alanine Aminotransferase (ALT)、Aspartate Aminotransferase (AST) <2.0×upper limit of normal (ULN)
• Adequate renal function: creatinine clearance ≥60 ml/min
• Satisfactory performance status: Karnofsky scale (KPS) ≥ 70
• Without radiotherapy or chemotherapy
• Patients must give signed informed consent

Exclusion Criteria:

• Evidence of relapse or distant metastasis
• History of prior malignancy or previous treatment for NPC
• 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.
• Pregnancy or lactation

Contacts and Locations

Contacts

Contact: Peiyu Huang, MD,PhD; +86-20-87343379; huangpy@sysucc.org.cn

Contact: Ming-Yuan Chen, MD,PhD; +86-20-87343361; chenmy@sysucc.org.cn

Locations

China, Guangdong

Sun Yat-sen University Cancer Center; Recruiting

Guangzhou, Guangdong, China, 510060

Contact: Rui-Hua Xu, MD,PhD

Sponsors and Collaborators

Sun Yat-sen University

Affiliated Cancer Hospital & Institute of Guangzhou Medical University

Guangdong Provincial People's Hospital

First Affiliated Hospital, Sun Yat-Sen University

Investigators

• Principal Investigator: Ming-Yuan Chen, MD,PhD; Sun Yat-sen University

More Information

• Responsible Party: Ming-Yuan Chen, Principal Investigator, Sun Yat-sen University
• ClinicalTrials.gov Identifier: NCT03840421
• Other Study ID Numbers: 2018-FXY-140
• First Posted: February 15, 2019
• Last Update Posted: October 22, 2020
• Last Verified: October 2020

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Ming-Yuan Chen, Sun Yat-sen University:

gemcitabine; cisplatin; fluorouracil

Additional relevant MeSH terms:

Carcinoma; Neoplasms; Nasopharyngeal Carcinoma; Head and Neck Neoplasms; Nasopharyngeal Neoplasms; Nasopharyngeal Diseases; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Neoplasms by Site; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases; Gemcitabine; Cisplatin; Fluorouracil; Antineoplastic Agents; Antimetabolites, Antineoplastic; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Antiviral Agents; Anti-Infective Agents; Enzyme Inhibitors; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs