Concurrent Chemotherapy for the Intermediate Risk Nasopharyngeal Carcinoma In Intensity-modulated Radiotherapy Era

NCT ID: NCT02633202

Last Updated: 2018-12-13

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE3

Total Enrollment

338 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-11-30

Study Completion Date

2021-12-31

Brief Summary

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Currently, concurrent chemoradiotherapy with/without sequential chemotherapy is the standard treatment modality for intermediate risk NPC (stage II and T3N0M0) according to the National Comprehensive Cancer Network guideline. However these recommendations were based on the evidence in the two-dimensional conventional radiotherapy (2DCRT) era. The introduction of intensity-modulated radiotherapy (IMRT) in NPC treatment has brought substantial better treatment outcomes than 2DCRT. It has been questioned whether additional concurrent chemotherapy is still necessary for intermediate risk NPC within the excellent framework of IMRT. Thus, the investigators jointly conduct the first non-inferior randomized trial to determine the value of concurrent chemotherapy with cisplatin for intermediate risk NPC patients treated with IMRT. Given the results of clinical studies mentioned above,the investigators decide to adopt the concurrent regimen to be cisplatin 100 mg/m2 on day 1, 22, 43

Detailed Description

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Currently, concurrent chemoradiotherapy with/without sequential chemotherapy is the standard treatment modality for intermediate risk NPC (stage II and T3N0M0) according to the National Comprehensive Cancer Network guideline. However these recommendations were based on the evidence in the two-dimensional conventional radiotherapy (2DCRT) era. The introduction of intensity-modulated radiotherapy (IMRT) in NPC treatment has brought substantial better treatment outcomes than 2DCRT. It has been questioned whether additional concurrent chemotherapy is still necessary for intermediate risk NPC within the excellent framework of IMRT. Thus, the investigators jointly conduct the first non-inferior randomized trial to determine the value of concurrent chemotherapy with cisplatin for intermediate risk NPC patients treated with IMRT. Given the results of clinical studies mentioned above, the investigators decide to adopt the concurrent regimen to be cisplatin 100 mg/m2 on day 1, 22, 43

Conditions

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Nasopharyngeal Carcinoma

Keywords

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Nasopharyngeal carcinoma Concurrent chemoradiotherapy intermediate risk intensity-modulated radiotherapy

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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RT group

intensity modulated-radiotherapy (IMRT) alone: Patients receive intensity modulated-radiotherapy (IMRT) alone

Group Type EXPERIMENTAL

IMRT

Intervention Type RADIATION

Intensity modulated-radiotherapy (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

CCRT group

IMRT and concurrent cisplatin Patients receive intensity modulated-radiotherapy (IMRT), concurrently with cisplatin 100 mg/m² every 3 weeks for 3 cycles

Group Type ACTIVE_COMPARATOR

IMRT

Intervention Type RADIATION

Intensity modulated-radiotherapy (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

Cisplatin

Intervention Type DRUG

concurrently with cisplatin 100 mg/m² every 3 weeks for 3 cycles during IMRT

Interventions

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IMRT

Intensity modulated-radiotherapy (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

Intervention Type RADIATION

Cisplatin

concurrently with cisplatin 100 mg/m² every 3 weeks for 3 cycles during IMRT

Intervention Type DRUG

Other Intervention Names

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Intensity-modulated radiation therapy Concurrent cisplatin regimen

Eligibility Criteria

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Inclusion Criteria

* Patients with newly histologically confirmed non-keratinizing (according to WHO histologically type.
* Tumor staged as T1-2N1/T2-3N0(according to the 7th AJCC edition).
* No evidence of distant metastasis (M0).
* Satisfactory performance status: Karnofsky scale (KPS) ≥ 70.
* Adequate marrow: leucocyte count ≥ 4000/μL, hemoglobin ≥ 120g/L for male, ≥ 120g/L for female , and platelet count ≥ 100000/μL.
* Normal liver function test: Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) \< 1.5×upper limit of normal (ULN) concomitant with alkaline phosphatase (ALP) ≤ 2.5×ULN, and bilirubin ≤ ULN.
* Adequate renal function: creatinine clearance ≥ 60 ml/min.
* Patients must be informed of the investigational nature of this study and give written informed consent.

Exclusion Criteria

* Neck lymph node with extracapsular spread. Maximal axial diameter of neck lymph node ≥30mm, positive neck lymph node at level IV and/or Vb.
* Pretreatment plasma EBV DNA level ≥4000 copy/ml.
* WHO Type keratinizing squamous cell carcinoma or basaloid squamous cell carcinoma.
* Age \> 65 or \< 18.
* Treatment with palliative intent.
* 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 RT (except for non-melanomatous skin cancers outside intended RT treatment volume).
* Prior 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
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Fifth Affiliated Hospital, Sun Yat-Sen University

OTHER

Sponsor Role collaborator

First People's Hospital of Foshan

OTHER

Sponsor Role collaborator

Guilin Medical University, China

OTHER

Sponsor Role collaborator

Sun Yat-sen University

OTHER

Sponsor Role lead

Responsible Party

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Lei Chen

M.D.

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Lei Chen, M.D.

Role: STUDY_CHAIR

Sun Yat-sen University

Locations

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Sun Yat-sen University Cancer Center

Guangzhou, Guangdong, China

Site Status RECRUITING

Countries

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China

Central Contacts

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Lei Chen, M.D.

Role: CONTACT

Phone: +86-20-87343096

Email: [email protected]

Facility Contacts

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Lei Chen, M.D.

Role: primary

References

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Chua DT, Sham JS, Kwong DL, Au GK. Treatment outcome after radiotherapy alone for patients with Stage I-II nasopharyngeal carcinoma. Cancer. 2003 Jul 1;98(1):74-80. doi: 10.1002/cncr.11485.

Reference Type BACKGROUND
PMID: 12833458 (View on PubMed)

Xiao WW, Han F, Lu TX, Chen CY, Huang Y, Zhao C. Treatment outcomes after radiotherapy alone for patients with early-stage nasopharyngeal carcinoma. Int J Radiat Oncol Biol Phys. 2009 Jul 15;74(4):1070-6. doi: 10.1016/j.ijrobp.2008.09.008. Epub 2009 Feb 21.

Reference Type BACKGROUND
PMID: 19231110 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 22056739 (View on PubMed)

Song CH, Wu HG, Heo DS, Kim KH, Sung MW, Park CI. Treatment outcomes for radiotherapy alone are comparable with neoadjuvant chemotherapy followed by radiotherapy in early-stage nasopharyngeal carcinoma. Laryngoscope. 2008 Apr;118(4):663-70. doi: 10.1097/MLG.0b013e3181626cfe.

Reference Type BACKGROUND
PMID: 18216741 (View on PubMed)

Chua DT, Ma J, Sham JS, Mai HQ, Choy DT, Hong MH, Lu TX, Au GK, Min HQ. Improvement of survival after addition of induction chemotherapy to radiotherapy in patients with early-stage nasopharyngeal carcinoma: Subgroup analysis of two Phase III trials. Int J Radiat Oncol Biol Phys. 2006 Aug 1;65(5):1300-6. doi: 10.1016/j.ijrobp.2006.02.016. Epub 2006 Jun 5.

Reference Type BACKGROUND
PMID: 16750333 (View on PubMed)

Xu T, Hu C, Wang X, Shen C. Role of chemoradiotherapy in intermediate prognosis nasopharyngeal carcinoma. Oral Oncol. 2011 May;47(5):408-13. doi: 10.1016/j.oraloncology.2011.03.008. Epub 2011 Apr 2.

Reference Type BACKGROUND
PMID: 21459659 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 20643517 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 22995588 (View on PubMed)

Lee AW, Ng WT, Chan LL, Hung WM, Chan CC, Sze HC, Chan OS, Chang AT, Yeung RM. Evolution of treatment for nasopharyngeal cancer--success and setback in the intensity-modulated radiotherapy era. Radiother Oncol. 2014 Mar;110(3):377-84. doi: 10.1016/j.radonc.2014.02.003. Epub 2014 Mar 11.

Reference Type BACKGROUND
PMID: 24630534 (View on PubMed)

Su SF, Han F, Zhao C, Chen CY, Xiao WW, Li JX, Lu TX. Long-term outcomes of early-stage nasopharyngeal carcinoma patients treated with intensity-modulated radiotherapy alone. Int J Radiat Oncol Biol Phys. 2012 Jan 1;82(1):327-33. doi: 10.1016/j.ijrobp.2010.09.011. Epub 2010 Oct 29.

Reference Type BACKGROUND
PMID: 21035959 (View on PubMed)

Tham IW, Lin S, Pan J, Han L, Lu JJ, Wee J. Intensity-modulated radiation therapy without concurrent chemotherapy for stage IIb nasopharyngeal cancer. Am J Clin Oncol. 2010 Jun;33(3):294-9. doi: 10.1097/COC.0b013e3181d2edab.

Reference Type BACKGROUND
PMID: 20395788 (View on PubMed)

Luo S, Zhao L, Wang J, Xu M, Li J, Zhou B, Xiao F, Long X, Shi M. Clinical outcomes for early-stage nasopharyngeal carcinoma with predominantly WHO II histology treated by intensity-modulated radiation therapy with or without chemotherapy in nonendemic region of China. Head Neck. 2014 Jun;36(6):841-7. doi: 10.1002/hed.23386. Epub 2013 Oct 4.

Reference Type BACKGROUND
PMID: 23720240 (View on PubMed)

Zhang F, Zhang Y, Li WF, Liu X, Guo R, Sun Y, Lin AH, Chen L, Ma J. Efficacy of Concurrent Chemotherapy for Intermediate Risk NPC in the Intensity-Modulated Radiotherapy Era: a Propensity-Matched Analysis. Sci Rep. 2015 Nov 27;5:17378. doi: 10.1038/srep17378.

Reference Type BACKGROUND
PMID: 26611462 (View on PubMed)

Tang LL, Guo R, Zhang N, Deng B, Chen L, Cheng ZB, Huang J, Hu WH, Huang SH, Luo WJ, Liang JH, Zheng YM, Zhang F, Mao YP, Li WF, Zhou GQ, Liu X, Chen YP, Xu C, Lin L, Liu Q, Du XJ, Zhang Y, Sun Y, Ma J. Effect of Radiotherapy Alone vs Radiotherapy With Concurrent Chemoradiotherapy on Survival Without Disease Relapse in Patients With Low-risk Nasopharyngeal Carcinoma: A Randomized Clinical Trial. JAMA. 2022 Aug 23;328(8):728-736. doi: 10.1001/jama.2022.13997.

Reference Type DERIVED
PMID: 35997729 (View on PubMed)

Other Identifiers

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IRNPC15

Identifier Type: -

Identifier Source: org_study_id