Concurrent Chemoradiotherapy With Nedaplatin Versus Cisplatin in Nasopharyngeal Carcinoma

A Randomized Phase III Non-inferiority Study of Concurrent Chemoradiotherapy With Nedaplatin Versus Cisplatin in Locoregionally Advanced Nasopharyngeal Carcinoma

This is a Phase III trial to study the effectiveness of nedaplatin versus cisplatin with IMRT chemoradiotherapy in treating patients with locoregionally advanced nasopharyngeal carcinoma.

Study Overview

• Status: Completed
• Conditions: Nasopharyngeal Carcinoma
• Intervention / Treatment: Drug: Nedaplatin; Drug: Cisplatin

Detailed Description

Nasopharyngeal carcinoma (NPC) is endemic in Southern China and Southeast Asia. Several prospective randomized trials have demonstrated that concurrent chemoradiotherapy was superior to radiotherapy alone in the treatment of locoregionally advanced NPC. Cisplatin-based chemotherapy has been shown to have higher response rates in NPC than noncisplatin regimens. However, the patients' compliance was unsatisfactory because the obvious gastrointestinal toxicity of cisplatin. Nedaplatin is the new second generation platinum and it has slight gastrointestinal reaction. Our trial is in order to study the effectiveness of nedaplatin or cisplatin with intensity-modulated radiation therapy (IMRT) chemoradiotherapy in treating patients with locoregionally advanced NPC.

• Study Type: Interventional
• Enrollment (Actual): 402
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510060
      • Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients with newly histologically confirmed non-keratinizing nasopharyngeal carcinoma, including WHO II or III
• Original clinical staged as T1-4N1-3 or T3-4N0（according to the 7th AJCC edition）
• No evidence of distant metastasis (M0)
• Male and no pregnant female
• Age between 18-65
• WBC ≥ 4,000/mm3 and PLT ≥ 100,000/mm3
• With normal liver function test (ALT、AST ≤ 2.5×ULN)
• With normal renal function test (Creatinine ≤ 1.5×ULN)
• Satisfactory performance status: Karnofsky scale (KPS)> 70
• Without radiotherapy or chemotherapy
• Patients must give signed informed consent

Exclusion Criteria:

• Patients have evidence of relapse or distant metastasis
• The presence of uncontrolled life-threatening illness
• Receiving other ways of anti-cancer therapy
• Receiving radiotherapy or chemotherapy
• Pregnancy or lactation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Nedaplatin; Nedplatin combine with IMRT	Drug: Nedaplatin; Nedaplatin 100mg/m2(3 weekly),D1,D22,D43 of RT; Other Names: NDP
ACTIVE_COMPARATOR: Cisplatin; Cisplatin combine with IMRT	Drug: Cisplatin; Cisplatin 100mg/m2(3 weekly),D1,D22,D43 of RT; Other Names: DDP

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progress-free survival	Progress-free survival is calculated from the date of randomization to the date of the first progress at any site.	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Distant Metastasis-Free Survival (DMFS)	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 years
Determine the toxic effects, both quantitatively and qualitatively, and quality of life (QoL) of these regimens in these patients.	Administration and Monitoring Patients will be evaluated in the clinic and eligibility and informed consent obtained. Patients will be monitored for clinical toxicity by standard NIH criteria. QoL was assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTCQLQ-C30) and EORTC QLQ Head and Neck. A time period of 4 weeks will constitute the time for clinical safety monitoring.	4 weeks
Complete Response (CR)	CR assessed by independent reviewers, according to the Modified Response Evaluation Criteria in Solid Tumors (RECIST) from the National Cancer Institute (NCI). Disease response evaluated after the completion of the chemoradiotherapy treatment. Complete response defined as the complete disappearance of the target and non-target lesion(s) identified at baseline after radiological evaluation by Magnetic Resonance Imaging (MRI) only.	after the completion of the chemoradiotherapy treatment (up to 9 weeks)
Overall Survival(OS)	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.	2 years
Locoregional Relapse-Free Survival(LRRFS)	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.	2 years
Anti-neoplasms sensitization effects of chemotherapy to radiotherapy	Tumor response will be evaluated by physical examination and nasopharyngoscopy when radiotherapy in 20Gy、40Gy、70Gy.	radiotherapy in 20Gy、40Gy、70Gy
Cost-effectiveness analysis	The determination of cost, including direct cost drug fees, inspection fees, expenses and nursing cost; cost-effectiveness analysis, such as cost-effectiveness ratio (ratio of the direct cost and short - and long-term curative effect) and incremental cost-effectiveness ratio (i.e., increasing costs and increase short or long-term efficacy ratio).	completion of chemoradiotherapy
Correlate effects of CCRT with biomarkers of response and predictors of long-term outcome	Early identification of patients who will have more aggressive disease soon after diagnosis has been a major goal, we will investigate the correlate effects of CCRT with biomarkers of response and predictors of long-term outcome in these patients.	before chemoradiotherapy and after chemoradiotherapy

Collaborators and Investigators

• Sponsor: Sun Yat-sen University
• Collaborators: The First Affiliated Hospital of Guangdong Pharmaceutical University; Guangzhou Medical University; Meizhou City Hospital Of Guangdong Provience
• Investigators: Principal Investigator: HaiQiang Mai, MD,Ph.D, Cancer center

Publications and helpful links

General Publications

• Ma J, Mai HQ, Hong MH, Min HQ, Mao ZD, Cui NJ, Lu TX, Mo HY. Results of a prospective randomized trial comparing neoadjuvant chemotherapy plus radiotherapy with radiotherapy alone in patients with locoregionally advanced nasopharyngeal carcinoma. J Clin Oncol. 2001 Mar 1;19(5):1350-7. doi: 10.1200/JCO.2001.19.5.1350.
• Zheng J, Wang G, Yang GY, Wang D, Luo X, Chen C, Zhang Z, Li Q, Xu W, Li Z, Wang D. Induction chemotherapy with nedaplatin with 5-FU followed by intensity-modulated radiotherapy concurrent with chemotherapy for locoregionally advanced nasopharyngeal carcinoma. Jpn J Clin Oncol. 2010 May;40(5):425-31. doi: 10.1093/jjco/hyp183. Epub 2010 Jan 19.
• Fuwa N, Kodaira T, Tachibana H, Nakamura T, Daimon T. Dose escalation study of nedaplatin with 5-fluorouracil in combination with alternating radiotherapy in patients with head and neck cancer. Jpn J Clin Oncol. 2007 Mar;37(3):161-7. doi: 10.1093/jjco/hyl138. Epub 2007 Mar 1.
• Tanaka T, Yukawa K, Umesaki N. Radiation reduces carboplatin sensitivity and enhances nedaplatin sensitivity in cervical squamous cell carcinoma in vitro. Eur J Gynaecol Oncol. 2007;28(5):352-5.
• Chen QY, Wen YF, Guo L, Liu H, Huang PY, Mo HY, Li NW, Xiang YQ, Luo DH, Qiu F, Sun R, Deng MQ, Chen MY, Hua YJ, Guo X, Cao KJ, Hong MH, Qian CN, Mai HQ. Concurrent chemoradiotherapy vs radiotherapy alone in stage II nasopharyngeal carcinoma: phase III randomized trial. J Natl Cancer Inst. 2011 Dec 7;103(23):1761-70. doi: 10.1093/jnci/djr432. Epub 2011 Nov 4.
• Chan AT, Teo PM, Ngan RK, Leung TW, Lau WH, Zee B, Leung SF, Cheung FY, Yeo W, Yiu HH, Yu KH, Chiu KW, Chan DT, Mok T, Yuen KT, Mo F, Lai M, Kwan WH, Choi P, Johnson PJ. Concurrent chemotherapy-radiotherapy compared with radiotherapy alone in locoregionally advanced nasopharyngeal carcinoma: progression-free survival analysis of a phase III randomized trial. J Clin Oncol. 2002 Apr 15;20(8):2038-44. doi: 10.1200/JCO.2002.08.149.
• Tang QN, Liu LT, Qi B, Guo SS, Luo DH, Sun R, Sun XS, Chen DP, Guo L, Mo HY, Wang P, Liu SL, Liang YJ, Li XY, Yang ZC, Chen QY, Mai HQ, Tang LQ. Effect of Concurrent Chemoradiotherapy With Nedaplatin vs Cisplatin on the Long-term Outcomes of Survival and Toxic Effects Among Patients With Stage II to IVB Nasopharyngeal Carcinoma: A 5-Year Follow-up Secondary Analysis of a Randomized Clinical Trial. JAMA Netw Open. 2021 Dec 1;4(12):e2138470. doi: 10.1001/jamanetworkopen.2021.38470.
• Tang LQ, Chen DP, Guo L, Mo HY, Huang Y, Guo SS, Qi B, Tang QN, Wang P, Li XY, Li JB, Liu Q, Gao YH, Xie FY, Liu LT, Li Y, Liu SL, Xie HJ, Liang YJ, Sun XS, Yan JJ, Wu YS, Luo DH, Huang PY, Xiang YQ, Sun R, Chen MY, Lv X, Wang L, Xia WX, Zhao C, Cao KJ, Qian CN, Guo X, Hong MH, Nie ZQ, Chen QY, Mai HQ. Concurrent chemoradiotherapy with nedaplatin versus cisplatin in stage II-IVB nasopharyngeal carcinoma: an open-label, non-inferiority, randomised phase 3 trial. Lancet Oncol. 2018 Apr;19(4):461-473. doi: 10.1016/S1470-2045(18)30104-9. Epub 2018 Feb 28.

Helpful Links

• cancer
• cisplatin
• nedaplatin

Study record dates

Study Major Dates

• Study Start: February 1, 2012
• Primary Completion (ACTUAL): May 1, 2014
• Study Completion (ACTUAL): July 1, 2016

Study Registration Dates

• First Submitted: February 22, 2012
• First Submitted That Met QC Criteria: February 27, 2012
• First Posted (ESTIMATE): February 28, 2012

Study Record Updates

• Last Update Posted (ESTIMATE): October 28, 2016
• Last Update Submitted That Met QC Criteria: October 27, 2016
• Last Verified: March 1, 2013

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; Nedaplatin
• Other Study ID Numbers: Sun Yat-sen University