Intensity-modulated Radiotherapy With or Without Concurrent Chemotherapy for Stage II Nasopharyngeal Carcinoma

Nasopharyngeal Carcinoma Clinical Trial

Official title:

Intensity-modulated Radiotherapy With or Without Concurrent Chemotherapy for Stage II Nasopharyngeal Carcinoma: a Phase 3 Non-inferior Multicenter Randomized Controlled Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02610010
• Other study ID #: 2015-FXY-066-Dept. of RT
• Status: Recruiting
• Phase: Phase 3
• First received: November 13, 2015
• Last updated: November 18, 2015
• Start date: November 2015
• Est. completion date: November 2025

Study information

• Verified date: November 2015
• Source: Sun Yat-sen University
• Contact: Fang-Yun Xie, M.D.
• Phone: +86-020-87342618
• Email: xiefy[@]sysucc.org.cn
• Is FDA regulated: No
• Health authority: China: Health and Family Planning Commission of Guangdong Province
• Study type: Interventional

Clinical Trial Summary

A prior phase III randomized trial showed considerable survival benefit from the combined treatment of cisplatin-based concurrent chemotherapy and two-dimensional conventional radiotherapy (2DCRT) for patients with stage II (the Chinese 1992 staging system) nasopharyngeal carcinoma. However, since intensity-modulated radiotherapy (IMRT) was known to be superior to 2DCRT in local control, progression free survival and even overall survival, it is a pivotal question whether stage II [T1N1M0 and T2N0-1M0, based on the 2010 International Union against Cancer/American Joint Committee on Cancer (UICC/AJCC) staging system] patients can still obtain significant benefit from the additional concurrent chemotherapy in the IMRT era.

The investigators' retrospective study (PMID:26528755 ) indicated that low risk nasopharyngeal carcinoma (T1N1M0, T2N0-1M0 or T3N0M0, the 2010 UICC/AJCC staging system) patients who underwent IMRT could not benefit from cisplatin-based concurrent chemotherapy. Therefore, the investigators perform this randomized controlled trial to address this question, on a prudent assumption that IMRT alone was not inferior to IMRT plus concurrent chemotherapy in stage II patients.

Description:

Eligible patients are randomly assigned to receive intensity-modulated radiotherapy (IMRT) alone or IMRT plus concurrent chemotherapy. IMRT is given as 2.0-2.30 Gy per fraction with five daily fractions per week for 6-7 weeks to a total dose of 66 Gy or greater to the primary tumor. Concurrent chemotherapy consisted of cisplatin 100 mg/m² every 3 weeks for 3 cycles. The primary endpoint is overall survival (OS). Secondary end points include failure-free survival(FFS), locoregional relapse-free survival (LRFS), distant metastasis-free survival (DMFS), toxic effects and quality of life. All efficacy analyses are conducted in the intention-to-treat population, and the safety population include only patients who receive their randomly assigned treatment.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 462
• Est. completion date: November 2025
• Est. primary completion date: November 2022
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• Newly histologically confirmed non-keratinizing (WHO 1991) nasopharyngeal carcinoma.

• Tumor staged as T1N1M0 or T2N0-1M0 (the 2010 UICC/AJCC staging system).

• Karnofsky scale (KPS) = 70.

• Adequate marrow: leucocyte count = 4×10E9/L, hemoglobin = 110g/L and platelet count = 100×10E9/L.

• Normal liver function test: Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and bilirubin = 1.5×upper limit of normal (ULN) concomitant with alkaline phosphatase (ALP) = 2.5×ULN.

• Adequate renal function: creatinine clearance = 60 ml/min or creatinine = 1.5×ULN.

• Patients must give written informed consent.

Exclusion Criteria:

• Prior malignancy, except adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer.

• Pregnancy or lactation (consider pregnancy test in women of child-bearing age and emphasize effective contraception during the treatment period).

• History of previous radiotherapy (except for non-melanomatous skin cancers outside intended radiotherapy volume).

• Prior radiotherapy, chemotherapy or surgery (except diagnostic) to primary tumor or nodes.

• 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.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma
• Nasopharyngeal Carcinoma
• Nasopharyngeal Neoplasms

Intervention

Drug:
• Cisplatin
Cisplatin 100 mg/m² every 3 weeks for 3 cycles during radiotherapy.

Radiation:
• Intensity-modulated radiotherapy
Intensity-modulated radiotherapy

Locations

Country	Name	City	State
China	Sun Yat-sen University Cancer Center	Guangzhou	Guangdong

Sponsors (4)

Lead Sponsor	Collaborator
Sun Yat-sen University	Affiliated Tumor Hospital of Guangzhou Medical University, The First Affiliated Hospital of Guangdong Pharmaceutical University, The First Affiliated Hospital of Guangzhou Medical University

Country where clinical trial is conducted

China, 

References & Publications (6)

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. — View Citation

Lai SZ, Li WF, Chen L, Luo W, Chen YY, Liu LZ, Sun Y, Lin AH, Liu MZ, Ma J. How does intensity-modulated radiotherapy versus conventional two-dimensional radiotherapy influence the treatment results in nasopharyngeal carcinoma patients? Int J Radiat Oncol Biol Phys. 2011 Jul 1;80(3):661-8. doi: 10.1016/j.ijrobp.2010.03.024. Epub 2010 Jul 17. — View Citation

Peng G, Wang T, Yang KY, Zhang S, Zhang T, Li Q, Han J, Wu G. A prospective, randomized study comparing outcomes and toxicities of intensity-modulated radiotherapy vs. conventional two-dimensional radiotherapy for the treatment of nasopharyngeal carcinoma. Radiother Oncol. 2012 Sep;104(3):286-93. doi: 10.1016/j.radonc.2012.08.013. Epub 2012 Sep 17. — View Citation

Su Z, Mao YP, Tang J, Lan XW, OuYang PY, Xie FY. Long-term outcomes of concurrent chemoradiotherapy versus radiotherapy alone in stage II nasopharyngeal carcinoma treated with IMRT: a retrospective study. Tumour Biol. 2015 Oct 25. [Epub ahead of print] — View Citation

Zhang LN, Gao YH, Lan XW, Tang J, Su Z, Ma J, Deng W, OuYang PY, Xie FY. Propensity score matching analysis of cisplatin-based concurrent chemotherapy in low risk nasopharyngeal carcinoma in the intensity-modulated radiotherapy era. Oncotarget. 2015 Dec 22;6(41):44019-29. doi: 10.18632/oncotarget.5806. — View Citation

Zhang MX, Li J, Shen GP, Zou X, Xu JJ, Jiang R, You R, Hua YJ, Sun Y, Ma J, Hong MH, Chen MY. Intensity-modulated radiotherapy prolongs the survival of patients with nasopharyngeal carcinoma compared with conventional two-dimensional radiotherapy: A 10-year experience with a large cohort and long follow-up. Eur J Cancer. 2015 Nov;51(17):2587-95. doi: 10.1016/j.ejca.2015.08.006. Epub 2015 Aug 26. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall survival		Two year	Yes
Secondary	failure-free survival		two year	Yes
Secondary	distant metastasis-free survival		two year	Yes
Secondary	locoregional relapse-free survival		two year	Yes
Secondary	Number of participants with treatment-related acute adverse events as assessed by CTCAE v4.0		two months	Yes
Secondary	quality of life assessing by questionnaires		through study completion, an average of 5 year	Yes