Study of Neoadjuvant Gemcitabine and Cisplatin in Locoregionally Advanced Nasopharyngeal Carcinoma

Nasopharyngeal Carcinoma Clinical Trial

Official title:

Randomized Phase Ⅱ Trial of Induction Chemotherapy Using Gemcitabine and Cisplatin in Concurrence With Intensity-modulated Radiotherapy for Locoregionally Advanced Nasopharyngeal Carcinoma

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01417390
• Other study ID #: FSHNG-1108
• Status: Recruiting
• Phase: Phase 2
• First received: August 15, 2011
• Last updated: March 6, 2014
• Start date: November 2011
• Est. completion date: December 2015

Study information

• Verified date: March 2014
• Source: First People's Hospital of Foshan
• Contact: Wei wei Hong, M.D.
• Phone: +86-757-83162835
• Email: wwhong[@]fsyyy.com
• Is FDA regulated: No
• Health authority: China: Ethics Committee
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to compare induction chemotherapy (gemcitabine+cisplatin) plus concurrent chemoradiotherapy with concurrent chemoradiotherapy in patients with locoregionally advanced nasopharyngeal carcinoma (NPC), in order to confirm the value of induction chemotherapy using gemcitabine and cisplatin in NPC patients.

Description:

Patients presented with non-keratinizing NPC and stage Ⅲ-Ⅳb T3-4N1M0/TxN2-3M0 are randomly assigned to receive induction chemotherapy (gemcitabine+cisplatin) plus concurrent chemoradiotherapy (investigational arm) or concurrent chemoradiotherapy (control arm). Patients in both arms receive radical Intensity modulated radiation therapy (Trilogy, Varian), and cisplatin (40mg/m2) every weeks for six cycles during radiotherapy. Radiation is delivered to GTV at 70 Gy in 30 fractions, CTV1 at at 60 Gy in 30 fractions and CTV2 at 54 Gy in 30 fractions. Patients in the investigational arm receive gemcitabine (1000mg/m2 on day 1,8) and cisplatin (20mg/m2 on day 1-4) every three weeks for two cycles before the radiotherapy. The primary end point is response rates after radiotherapy, failure-free survival (FFS) and toxic effects and treatment compliance. Secondary end points include overall survival (OS), distant failure-free survival (D-FFS), locoregional failure-free survival (LR-FFS). All efficacy analyses are conducted in the intention-to-treat population; the safety population include only patients who receive their randomly assigned treatment.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 80
• Est. completion date: December 2015
• Est. primary completion date: December 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 60 Years

Eligibility

Inclusion Criteria:

• Patients with newly histologically confirmed non-keratinizing (according to World Health Organization (WHO 2005) histologically type).

• Karnofsky scale (KPS) > 70.

• Tumor staged is according to the 7th American Joint Commission on Cancer edition as Stage III:T1-2N2M0, T3N0-2M0 Stage IVa:T4N0-2M0 Stage IVb:Any T?N3.

• Adequate marrow: leucocyte count =4000/µL, hemoglobin =90g/L 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:

• WHO Type keratinizing squamous cell carcinoma.

• Age >60 years or <18 years.

• Treatment with palliative intent.

• Pregnancy or lactation.

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

• Any severe intercurrent disease including unstable cardiac disease, chronic hepatitis, renal disease, diabetes with poor control, and emotional disturbance.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Single Blind (Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma
• Nasopharyngeal Carcinoma
• Nasopharyngeal Neoplasms

Intervention

Drug:
• Drug: Gemcitabine and cisplatin
Patients receive Gemcitabine (1000mg/m2 on day 1,8) and cisplatin (20mg/m2 on day 1-4) every three weeks for two cycles before the radiotherapy, then receive radical radiotherapy with IMRT and cisplatin (40mg/m2) every week for six cycles during radiotherapy.
• Cisplatin
Patients receive radical radiotherapy and cisplatin (40mg/m2) every week for six cycles during radiotherapy

Locations

Country	Name	City	State
China	Wei-wei Hong	Foshan	Guangdong

Sponsors (1)

Lead Sponsor	Collaborator
First People's Hospital of Foshan

Country where clinical trial is conducted

China, 

References & Publications (6)

Benasso M, Merlano M, Sanguineti G, Corvò R, Numico G, Ricci I, Pallestrini E, Santelli A, Vitale V, Marchetti G, Rosso R. Gemcitabine, cisplatin, and radiation in advanced, unresectable squamous cell carcinoma of the head and neck: a feasibility study. Am J Clin Oncol. 2001 Dec;24(6):618-22. — View Citation

Chua DT, Sham JS, Au GK. Induction chemotherapy with cisplatin and gemcitabine followed by reirradiation for locally recurrent nasopharyngeal carcinoma. Am J Clin Oncol. 2005 Oct;28(5):464-71. — View Citation

Drössigk U, Hiepe T, Pötzsch F, Scholz D, Tietz HJ. Stimulation of human immunodeficiency virus expression in permanent monocytic cells by Sarcocystis gigantea extract. Parasitol Res. 1998 Jun;84(6):455-8. — 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

Lowy AM, Firdaus I, Roychowdhury D, Redmond K, Howington JA, Sussman JJ, Safa M, Ahmad SA, Reed MF, Rose P, James L, Jazieh AR. A phase II study of sequential neoadjuvant gemcitabine and paclitaxel, radiation therapy with cisplatin and 5-fluorouracil and surgery in locally advanced esophageal carcinoma. Am J Clin Oncol. 2006 Dec;29(6):555-61. — 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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Failure-free survival	Failure-free survival is calculated from the date of randomization to the date of the first failure at any site.	3-year	No
Secondary	Overall survival	Overall survival is calculated from randomization to death from any cause.	3-year	No
Secondary	Locoregional failure-free survival	the latency to the first local failure	3-year	No
Secondary	Distant failure-free survival	The latency to the first remote failure	3-year	No
Secondary	The initial response rates after treatments		16 weeks after completion of radiotherapy	No