Induction Chemotherapy With GP Versus TPF in the Treatment of Advanced Nasopharyngeal Carcinoma

Nasopharyngeal Carcinoma Clinical Trial

Official title:

Phase II Study Comparing Gemcitabine Plus Cisplatin to Docetaxel, Cisplatin, and Fluorouracil Induction Chemotherapy Followed by Chemoradiotherapy in Locally Advanced Nasopharyngeal Carcinoma

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT02016417
• Other study ID #: CHGX20131212
• Status: Not yet recruiting
• Phase: Phase 2
• First received: December 15, 2013
• Last updated: April 15, 2014
• Start date: May 2014
• Est. completion date: December 2020

Study information

• Verified date: December 2013
• Source: Cancer Hospital of Guangxi Medical University
• Contact: xiaodong Zhu, Doctor
• Phone: 867715331466
• Email: zhuxiaodong83[@]163.com
• Is FDA regulated: No
• Health authority: National Health and Family Planning Commission of the People's Republic of China:China
• Study type: Interventional

Clinical Trial Summary

The present study is a randomized, control, phase II study of locally advanced nasopharyngeal carcinoma (NPC) treated with Gemcitabine plus cisplatin regimen (GP) or Docetaxel，cisplatin regimen plus 5-Fluorouracil (TPF) induction chemotherapy followed by concurrent chemoradiotherapy.

Description:

Nasopharyngeal carcinoma (NPC) prevalence is reported to be highest in southern China, where an average of 80 cases per 100,000 population are reported each year. Nasopharyngeal carcinoma is both radiosensitive and chemosensitive. The National Comprehensive Cancer Network (NCCN) guidelines (version 1, 2013), have recommended use of concurrent chemoradiotherapy (CCRT) with or without adjuvant chemotherapy (AC) and induction chemotherapy (IC) followed by CCRT plus AC as standard treatment for NPC. However, it was unclear whether patients with NPC could benefit from IC. Recently, many new drugs including docetaxel and gemcitabine have been incorporated in the induction chemotherapy phase of NPC. The investigators designed the present study with induction chemotherapy follow by CCRT for locoregionally advanced NPC, comparing induction chemotherapy regime of gemcitabine plus cisplatin (GP) and docetaxel, cisplatin, and fluorouracil (TPF).

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 120
• Est. completion date: December 2020
• Est. primary completion date: December 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

1. Patients with newly histologically confirmed non-keratinizing (according to WHO histologically type).

2. 18 years to 70 years;

3. Tumor staged as T3-4N1/N2-3M0 (according to the 7th AJCC edition),

4. Performance status: Karnofsky scale (KPS) > 70 (Appendix I ).

5. Adequate marrow: leucocyte count > 4×109/L, neutrophil count > 2×109/L, hemoglobin > 90g/L and platelet count > 100×109/L.

6. 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.

7. Adequate renal function: creatinine clearance > 60 ml/min.

8. Patients must be informed of the investigational nature of this study and give written informed consent.

Exclusion Criteria:

1. WHO Type keratinizing squamous cell carcinoma or basaloid squamous cell carcinoma.

2. Age > 70 or < 18.

3. Treatment with palliative intent.

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

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

6. History of previous RT (except for non-melanomatous skin cancers outside intended RT treatment volume).

7. Prior chemotherapy or surgery (except diagnostic) to primary tumor or nodes.

8. 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: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma
• Nasopharyngeal Carcinoma
• Nasopharyngeal Neoplasms

Intervention

Drug:
• A combination of Gemcitabine and cisplatin
The GP regimen consists of gemcitabine at a dose of 1,000 mg/m2 by intravenous (i.v.) infusion over 30 min on day 1 and day 8, and cisplatin 80 mg/m2 by i.v. infusion for 4 h on day 1-3, The regime will be repeated every 3 weeks up to a total of 2-3 courses. Concurrent chemoradiotherapy is administrated with 3 cycles of weekly Cisplatin 100 mg/m2 starting on the first day of IMRT.
• A combination of Docetaxel, cisplatin and 5-Fluorouracil
The TPF regimen consists of docetaxel at a dose of 60 mg/m2/day on day 1, cisplatin 60 mg/m2 by i.v. infusion for 4 h on day 1-3, plus 5-Fluorouracil 600 mg/m2 CIV over 120 hours. The regime will be repeated every 3 weeks up to a total of 2-3 courses. Concurrent chemoradiotherapy is administrated with 3 cycles of weekly Cisplatin 100 mg/m2 starting on the first day of IMRT.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Cancer Hospital of Guangxi Medical University

References & Publications (18)

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Chan AT, Teo PM, Johnson PJ. Nasopharyngeal carcinoma. Ann Oncol. 2002 Jul;13(7):1007-15. Review. — View Citation

Fong KW, Chua EJ, Chua ET, Khoo-Tan HS, Lee KM, Lee KS, Sethi VK, Tan BC, Tan TW, Wee J, Yang TL. Patient profile and survival in 270 computer tomography-staged patients with nasopharyngeal cancer treated at the Singapore General Hospital. Ann Acad Med Singapore. 1996 May;25(3):341-6. — View Citation

Foo KF, Tan EH, Leong SS, Wee JT, Tan T, Fong KW, Koh L, Tai BC, Lian LG, Machin D. Gemcitabine in metastatic nasopharyngeal carcinoma of the undifferentiated type. Ann Oncol. 2002 Jan;13(1):150-6. — View Citation

Fountzilas G, Ciuleanu E, Bobos M, Kalogera-Fountzila A, Eleftheraki AG, Karayannopoulou G, Zaramboukas T, Nikolaou A, Markou K, Resiga L, Dionysopoulos D, Samantas E, Athanassiou H, Misailidou D, Skarlos D, Ciuleanu T. Induction chemotherapy followed by concomitant radiotherapy and weekly cisplatin versus the same concomitant chemoradiotherapy in patients with nasopharyngeal carcinoma: a randomized phase II study conducted by the Hellenic Cooperative Oncology Group (HeCOG) with biomarker evaluation. Ann Oncol. 2012 Feb;23(2):427-35. doi: 10.1093/annonc/mdr116. Epub 2011 Apr 27. — View Citation

He X, Ou D, Ying H, Zhu G, Hu C, Liu T. Experience with combination of cisplatin plus gemcitabine chemotherapy and intensity-modulated radiotherapy for locoregionally advanced nasopharyngeal carcinoma. Eur Arch Otorhinolaryngol. 2012 Mar;269(3):1027-33. doi: 10.1007/s00405-011-1669-9. Epub 2011 Jun 26. Erratum in: Eur Arch Otorhinolaryngol. 2012 Mar;269(3):1035. Xiayun, He [corrected to He, Xiayun].. — View Citation

Heng DM, Wee J, Fong KW, Lian LG, Sethi VK, Chua ET, Yang TL, Khoo Tan HS, Lee KS, Lee KM, Tan T, Chua EJ. Prognostic factors in 677 patients in Singapore with nondisseminated nasopharyngeal carcinoma. Cancer. 1999 Nov 15;86(10):1912-20. — View Citation

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Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011 Mar-Apr;61(2):69-90. doi: 10.3322/caac.20107. Epub 2011 Feb 4. Erratum in: CA Cancer J Clin. 2011 Mar-Apr;61(2):134. — View Citation

Jiang Y, Wei YQ, Luo F, Zou LQ, Liu JY, Peng F, Huang MJ, He QM. Gemcitabine and cisplatin in advanced nasopharyngeal carcinoma: a pilot study. Cancer Invest. 2005;23(2):123-8. — View Citation

Lorch JH, Goloubeva O, Haddad RI, Cullen K, Sarlis N, Tishler R, Tan M, Fasciano J, Sammartino DE, Posner MR; TAX 324 Study Group. Induction chemotherapy with cisplatin and fluorouracil alone or in combination with docetaxel in locally advanced squamous-cell cancer of the head and neck: long-term results of the TAX 324 randomised phase 3 trial. Lancet Oncol. 2011 Feb;12(2):153-9. doi: 10.1016/S1470-2045(10)70279-5. Epub 2011 Jan 11. — View Citation

Ma BB, Tannock IF, Pond GR, Edmonds MR, Siu LL. Chemotherapy with gemcitabine-containing regimens for locally recurrent or metastatic nasopharyngeal carcinoma. Cancer. 2002 Dec 15;95(12):2516-23. — View Citation

Ngan RK, Yiu HH, Lau WH, Yau S, Cheung FY, Chan TM, Kwok CH, Chiu CY, Au SK, Foo W, Law CK, Tse KC. Combination gemcitabine and cisplatin chemotherapy for metastatic or recurrent nasopharyngeal carcinoma: report of a phase II study. Ann Oncol. 2002 Aug;13(8):1252-8. — View Citation

Posner MR, Hershock DM, Blajman CR, Mickiewicz E, Winquist E, Gorbounova V, Tjulandin S, Shin DM, Cullen K, Ervin TJ, Murphy BA, Raez LE, Cohen RB, Spaulding M, Tishler RB, Roth B, Viroglio Rdel C, Venkatesan V, Romanov I, Agarwala S, Harter KW, Dugan M, Cmelak A, Markoe AM, Read PW, Steinbrenner L, Colevas AD, Norris CM Jr, Haddad RI; TAX 324 Study Group. Cisplatin and fluorouracil alone or with docetaxel in head and neck cancer. N Engl J Med. 2007 Oct 25;357(17):1705-15. — View Citation

Teo P, Yu P, Lee WY, Leung SF, Kwan WH, Yu KH, Choi P, Johnson PJ. Significant prognosticators after primary radiotherapy in 903 nondisseminated nasopharyngeal carcinoma evaluated by computer tomography. Int J Radiat Oncol Biol Phys. 1996 Sep 1;36(2):291-304. — View Citation

Yau TK, Lee AW, Wong DH, Yeung RM, Chan EW, Ng WT, Tong M, Soong IS. Induction chemotherapy with cisplatin and gemcitabine followed by accelerated radiotherapy and concurrent cisplatin in patients with stage IV(A-B) nasopharyngeal carcinoma. Head Neck. 2006 Oct;28(10):880-7. — View Citation

Yoshizaki T, Ito M, Murono S, Wakisaka N, Kondo S, Endo K. Current understanding and management of nasopharyngeal carcinoma. Auris Nasus Larynx. 2012 Apr;39(2):137-44. doi: 10.1016/j.anl.2011.02.012. Epub 2011 May 17. Review. — View Citation

Zhang L, Zhang Y, Huang PY, Xu F, Peng PJ, Guan ZZ. Phase II clinical study of gemcitabine in the treatment of patients with advanced nasopharyngeal carcinoma after the failure of platinum-based chemotherapy. Cancer Chemother Pharmacol. 2008 Jan;61(1):33-8. Epub 2007 Mar 20. — View Citation

* Note: There are 18 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Failure-free survival (FFS)	From the date of registration to the date of either locally, regionally or distant failure or last follow-up	One year	No
Secondary	Overall survival (OS)	Survival from the date of registration to the date of death or last follow-up	One year	No
Secondary	Loco-regional failure-free survival (LFFS)	Survival from the date of registration to the date of either locally, regional recurrence or last follow-up	One year	No
Secondary	Distant metastasis failure-free survival (DMFS)	Survival from the date of registration to the date of either distant metastasis or last follow-up	One year	No
Secondary	Acute induction chemotherapy toxicity	The side effects will be evaluated according to NCI-CTC AE V 3.0.	Two months	Yes

External Links

•   Drug Information available for: Cisplatin, Gemcitabine, Docetaxel and Fluorouracil
•   Genetic and Rare Diseases Information Center resources: Nasopharyngeal Carcinoma
•   Guangxi Medical University
•   MedlinePlus related topics: Cancer
•   National Health and Family Planning Commission of the People's Republic of China
•   U.S. FDA Resources