Clinical trial NCT01540136: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Nasopharyngeal Carcinoma
Lead sponsor: Sun Yat-sen University
Sponsor class: OTHER
Collaborators: name: Guangzhou Medical University
name: The First Affiliated Hospital of Guangdong Pharmaceutical University
name: Meizhou City Hospital Of Guangdong Provience
First posted: 2012-02-28
Enrollment: 402
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Progress-free survival
timeFrame: 2 years
Secondary outcomes:
measure: Determine the toxic effects, both quantitatively and qualitatively, and quality of life (QoL) of these regimens in these patients.
timeFrame: 4 weeks
measure: Complete Response (CR)
timeFrame: after the completion of the chemoradiotherapy treatment (up to 9 weeks)
measure: Overall Survival(OS)
timeFrame: 2 years
measure: Locoregional Relapse-Free Survival(LRRFS)
timeFrame: 2 years
measure: Distant Metastasis-Free Survival (DMFS)
timeFrame: 2 years
measure: Anti-neoplasms sensitization effects of chemotherapy to radiotherapy
timeFrame: radiotherapy in 20Gy、40Gy、70Gy
measure: Cost-effectiveness analysis
timeFrame: completion of chemoradiotherapy
measure: Correlate effects of CCRT with biomarkers of response and predictors of long-term outcome
timeFrame: before chemoradiotherapy and after chemoradiotherapy
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center
state: Guangdong
Study officials:
affiliation: Cancer center
name: HaiQiang Mai, MD,Ph.D
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.