Study to Evaluate Induction Chemotherapy Using Docetaxel, Cisplatin and Fluorouracil in Concurrence With Intensity-modulated Radiotherapy for Local Recurrent Nasopharyngeal Carcinoma (NPC)

Nasopharyngeal Carcinoma Clinical Trial

Official title:

Phase II Study to Evaluate Induction Chemotherapy Using Docetaxel, Cisplatin and Fluorouracil Followed by Weekly Docetaxel and Cetuximab in Concurrence With Intensity-modulated Radiotherapy for Locally Recurrent Nasopharyngeal Carcinoma (NPC)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01326559
• Other study ID #: NPC-1001 trial
• Status: Completed
• Phase: Phase 2
• First received: March 22, 2011
• Last updated: August 13, 2017
• Start date: June 2010
• Est. completion date: March 2017

Study information

• Verified date: August 2017
• Source: Hong Kong Nasopharyngeal Cancer Study Group Limited
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Study Objective:

Primary

1. To evaluate the complete response (CR) rate with induction chemotherapy using Docetaxel, Cisplatin and Fluorouracil(TPF) followed by Docetaxel plus Cetuximab (TC) in concurrence with intensity-modulated radiotherapy (IMRT).

Secondary

1. To determine the overall response rate.

2. To determine the locoregional and distant control rate

3. To determine the progression-free survival (PFS)

4. To determine the overall survival (OS)

5. To determine the safety of the induction chemotherapy and concurrent chemoradiation plus Cetuximab.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 33
• Est. completion date: March 2017
• Est. primary completion date: December 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

Inclusion criteria:

• Recurrent T3N0-N1M0 NPC (by AJCC/UICC 6th edition) and at least 1 year from the end of last primary course of radiotherapy

• Age > 18 to < 70 years

• Performance status: < 1 by ECOG System (Appendix I)

• Adequate bone marrow & renal function

• Patients having Bilirubin =< 1.5 x ULN, ASAT & ALST=< 1.5 x ULN, Serum creatinine=< 1.25 x ULN and / or Creatinine clearance >= 60ml/min

• Patients having WBC >= 3x10e9/L, Neutrophils 1.8x10e9/L, Platelets >= 100 x10e9/L,Hemoglobin >=10g/dL

• Signed written informed consent

• Patients must have at least one measurable lesion

Exclusion Criteria:

• Use of investigational agent within the past 28 days

• Pre-treatment with an anti-EGFR drug

• Severe cardiac disease such as heart failure, coronary artery disease or myocardial infarction within the last 12 months

• History of severe pulmonary diseases

• Active infection or other systemic disease under poor control

• Uncontrolled chronic neuropathy

• Know grade 3 or 4 allergic reaction to any of the components of the treatment

• Estimated life expectancy is less than 3 months

• Pregnancy or breast feeding

Related Conditions & MeSH terms

• Carcinoma
• Nasopharyngeal Carcinoma
• Nasopharyngeal Neoplasms

Intervention

Drug:
• Docetaxel, Cisplatin, 5-FU and Cetuximab
Induction phase (Weeks 1-9): Drug Docetaxel Docetaxel 75 mg/m2 IV, D1 every 3 weeks for 3 cycles Drug Cisplatin Cisplatin 75 mg/m2 IV, D1 every 3 weeks for 3 cycles Drug Fluorouracil Fluorouracil 750 mg/m2 IV, D1-4 every 3 weeks for 3 cycles Concurrent phase (weeks 10-16): Drug Docetaxel Docetaxel 15 mg/m2 IV, D1 weekly for 7 weeks (Weeks 10-16) Drug Cetuximab Cetuximab 400 mg m2 IV, D1 initial dose, then 250 mg/m2 weekly for 7 week (Weeks 10-16) IMRT (60 Gy to GTV or biological dose equivalent): 2 Gy/fraction/day, D1-5 per week, for 6 weeks (Weeks 11-16)

Locations

Country	Name	City	State
China	Department of Clinical Oncology, Queen Mary Hospital	Hong Kong
China	Department of Clinical Oncology, Queen Mary Hospital(QMH), Hong Kong	Hong Kong
China	Department of Clinical Oncology, Tuen Mun Hospital (TMH), Hong Kong	Hong Kong
China	Department of Oncology, Princess Margaret Hospital	Hong Kong

Sponsors (5)

Lead Sponsor	Collaborator
Hong Kong Nasopharyngeal Cancer Study Group Limited	Merck Sharp & Dohme Corp., Roche Pharma AG, Sanofi, The University of Hong Kong

Country where clinical trial is conducted

China, 

References & Publications (14)

Bonner JA, Harari PM, Giralt J, Azarnia N, Shin DM, Cohen RB, Jones CU, Sur R, Raben D, Jassem J, Ove R, Kies MS, Baselga J, Youssoufian H, Amellal N, Rowinsky EK, Ang KK. Radiotherapy plus cetuximab for squamous-cell carcinoma of the head and neck. N Engl J Med. 2006 Feb 9;354(6):567-78. — 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

Chua DT, Sham JS, Leung LH, Au GK. Re-irradiation of nasopharyngeal carcinoma with intensity-modulated radiotherapy. Radiother Oncol. 2005 Dec;77(3):290-4. Epub 2005 Nov 8. — View Citation

Fu KK, Newman H, Phillips TL. Treatment of locally recurrent carcinoma of the nasopharynx. Radiology. 1975 Nov;117(2):425-31. — View Citation

Leung TW, Tung SY, Sze WK, Sze WM, Wong VY, Wong CS, O SK. Salvage radiation therapy for locally recurrent nasopharyngeal carcinoma. Int J Radiat Oncol Biol Phys. 2000 Dec 1;48(5):1331-8. — View Citation

Lu TX, Mai WY, Teh BS, Zhao C, Han F, Huang Y, Deng XW, Lu LX, Huang SM, Zeng ZF, Lin CG, Lu HH, Chiu JK, Carpenter LS, Grant WH 3rd, Woo SY, Cui NJ, Butler EB. Initial experience using intensity-modulated radiotherapy for recurrent nasopharyngeal carcinoma. Int J Radiat Oncol Biol Phys. 2004 Mar 1;58(3):682-7. — View Citation

Nakata E, Hunter N, Mason K, Fan Z, Ang KK, Milas L. C225 antiepidermal growth factor receptor antibody enhances the efficacy of docetaxel chemoradiotherapy. Int J Radiat Oncol Biol Phys. 2004 Jul 15;59(4):1163-73. — View Citation

Poon D, Yap SP, Wong ZW, Cheung YB, Leong SS, Wee J, Tan T, Fong KW, Chua ET, Tan EH. Concurrent chemoradiotherapy in locoregionally recurrent nasopharyngeal carcinoma. Int J Radiat Oncol Biol Phys. 2004 Aug 1;59(5):1312-8. — 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

Pryzant RM, Wendt CD, Delclos L, Peters LJ. Re-treatment of nasopharyngeal carcinoma in 53 patients. Int J Radiat Oncol Biol Phys. 1992;22(5):941-7. — View Citation

Teo PM, Kwan WH, Chan AT, Lee WY, King WW, Mok CO. How successful is high-dose (> or = 60 Gy) reirradiation using mainly external beams in salvaging local failures of nasopharyngeal carcinoma? Int J Radiat Oncol Biol Phys. 1998 Mar 1;40(4):897-913. Review. — View Citation

Vermorken JB, Remenar E, van Herpen C, Gorlia T, Mesia R, Degardin M, Stewart JS, Jelic S, Betka J, Preiss JH, van den Weyngaert D, Awada A, Cupissol D, Kienzer HR, Rey A, Desaunois I, Bernier J, Lefebvre JL; EORTC 24971/TAX 323 Study Group. Cisplatin, fluorouracil, and docetaxel in unresectable head and neck cancer. N Engl J Med. 2007 Oct 25;357(17):1695-704. — View Citation

Wang CC. Re-irradiation of recurrent nasopharyngeal carcinoma--treatment techniques and results. Int J Radiat Oncol Biol Phys. 1987 Jul;13(7):953-6. — View Citation

Yan JH, Hu YH, Gu XZ. Radiation therapy of recurrent nasopharyngeal carcinoma. Report on 219 patients. Acta Radiol Oncol. 1983;22(1):23-8. — View Citation

* Note: There are 14 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Complete response rate	Complete response rate is defined as the proportion of subjects with disappearance of all target lesions after induction and concurrent therapies.	5 years
Secondary	Overall response rate	Defined as the proportion of subjects with best response (confirmed CR or PR) compared to the overall treated group.	5 years
Secondary	Locoregional and distant control rate	Defined as the proportion of subjects with no local or nodal progression or recurrence and no distant disease progression or recurrence compared to the overall treated group.	5 years
Secondary	Progression free survival	Defined as the time in months from first dose of cetuximab until PD is observed or death occurs due to any cause within 90 days after the last tumour assessment or first cetuximab dose.	5 years
Secondary	Overall survival	Defined as the time in months from first dose of cetuximab to the date of death is observed. If subject has not died, the survival time will be censored on the last date the subject was known to be alive.	5 years