Concurrent Chemoradiotherapy With Nedaplatin Versus Cisplatin in Nasopharyngeal Carcinoma

• ClinicalTrials.gov Identifier: NCT01540136
• Recruitment Status: Completed
• First Posted: February 28, 2012
• Last Update Posted: October 28, 2016
• Sponsor: Sun Yat-sen University
• Collaborators: Guangzhou Medical University; The First Affiliated Hospital of Guangdong Pharmaceutical University; Meizhou City Hospital Of Guangdong Provience
• Information provided by (Responsible Party): Hai-Qiang Mai,MD,PhD, Sun Yat-sen University

Tracking Information

• First Submitted Date: February 22, 2012
• First Posted Date: February 28, 2012
• Last Update Posted Date: October 28, 2016
• Study Start Date: February 2012
• Actual Primary Completion Date: May 2014 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 27, 2012)

Progress-free survival [ Time Frame: 2 years ]

Progress-free survival is calculated from the date of randomization to the date of the first progress at any site.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: September 2, 2013)

• Determine the toxic effects, both quantitatively and qualitatively, and quality of life (QoL) of these regimens in these patients. [ Time Frame: 4 weeks ]
  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.
• Complete Response (CR) [ Time Frame: after the completion of the chemoradiotherapy treatment (up to 9 weeks) ]
  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.
• Overall Survival(OS) [ Time Frame: 2 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.
• Locoregional Relapse-Free Survival(LRRFS) [ Time Frame: 2 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.
• Distant Metastasis-Free Survival (DMFS) [ Time Frame: 2 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.
• Anti-neoplasms sensitization effects of chemotherapy to radiotherapy [ Time Frame: radiotherapy in 20Gy、40Gy、70Gy ]
  Tumor response will be evaluated by physical examination and nasopharyngoscopy when radiotherapy in 20Gy、40Gy、70Gy.
• Cost-effectiveness analysis [ Time Frame: completion of chemoradiotherapy ]
  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).
• Correlate effects of CCRT with biomarkers of response and predictors of long-term outcome [ Time Frame: before chemoradiotherapy and after chemoradiotherapy ]
  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.

Original Secondary Outcome Measures (submitted: February 27, 2012)

• Determine the toxic effects, both quantitatively and qualitatively, of these regimens in these patients. [ Time Frame: 4 weeks ]
  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. A time period of 4 weeks will constitute the time for clinical safety monitoring.
• Complete Response (CR) [ Time Frame: after the completion of the chemoradiotherapy treatment (up to 9 weeks) ]
  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.
• Overall Survival(OS) [ Time Frame: 2 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.
• Locoregional Relapse-Free Survival(LRRFS) [ Time Frame: 2 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.
• Distant Metastasis-Free Survival (DMFS) [ Time Frame: 2 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.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Concurrent Chemoradiotherapy With Nedaplatin Versus Cisplatin in Nasopharyngeal Carcinoma
• Official Title: A Randomized Phase III Non-inferiority Study of Concurrent Chemoradiotherapy With Nedaplatin Versus Cisplatin in Locoregionally Advanced Nasopharyngeal Carcinoma
• Brief Summary: 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.
• 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
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Nasopharyngeal Carcinoma

Intervention

• Drug: Nedaplatin
  Nedaplatin 100mg/m2(3 weekly),D1,D22,D43 of RT
  Other Name: NDP
• Drug: Cisplatin
  Cisplatin 100mg/m2(3 weekly),D1,D22,D43 of RT
  Other Name: DDP

Study Arms

• Experimental: Nedaplatin
  Nedplatin combine with IMRT
  Intervention: Drug: Nedaplatin
• Active Comparator: Cisplatin
  Cisplatin combine with IMRT
  Intervention: Drug: Cisplatin

Publications *

• 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.
• 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.
• 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: October 17, 2016): 402
• Original Estimated Enrollment (submitted: February 27, 2012): 256
• Actual Study Completion Date: July 2016
• Actual Primary Completion Date: May 2014 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 65 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: China

Administrative Information

• NCT Number: NCT01540136
• Other Study ID Numbers: Sun Yat-sen University
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Hai-Qiang Mai,MD,PhD, Sun Yat-sen University
• Original Responsible Party: Same as current
• Current Study Sponsor: Sun Yat-sen University
• Original Study Sponsor: Same as current

Collaborators

• Guangzhou Medical University
• The First Affiliated Hospital of Guangdong Pharmaceutical University
• Meizhou City Hospital Of Guangdong Provience

Investigators

• Principal Investigator: HaiQiang Mai, MD,Ph.D; Cancer center

• PRS Account: Sun Yat-sen University
• Verification Date: March 2013