Therapeutic Gain by Induction-concurrent Chemoradiotherapy and/or Accelerated Fractionation for Nasopharyngeal Carcinoma

Nasopharyngeal Carcinoma Clinical Trial

Official title:

Randomized Trial to Evaluate Therapeutic Gain by Changing Chemoradiotherapy From Concurrent-adjuvant to Induction-concurrent Sequence, and Radiotherapy From Conventional to Accelerated Fractionation for Advanced Nasopharyngeal Carcinoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00379262
• Other study ID #: NPC-0501 Trial
• Status: Completed
• Phase: Phase 3
• Start date: September 2006
• Est. completion date: December 2018

Study information

• Verified date: August 2019
• Source: Hong Kong Nasopharyngeal Cancer Study Group Limited
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The objectives of this clinical study are threefold:

1. To compare the benefits in cancer control and survival obtained from adding induction-concurrent chemotherapy to radiation with those from adding concurrent-adjuvant chemotherapy to radiation.

2. To test whether replacing fluorouracil with Xeloda in combining with cisplatin in the chemotherapy plan will maintain or improve further the chemotherapy benefits while reducing the duration of hospital stay.

3. To see if accelerated fractionation radiotherapy can improve the outcome of patients as compared with conventional fractionation radiotherapy.

Description:

1. primary objectives include

1. comparing induction chemotherapy with Cisplatin + 5-Fluorouracil versus adjuvant chemotherapy with Cisplatin + 5-Fluorouracil(PF-Pvs P-PF)

2. comparing induction chemotherapy with Cisplatin + Capecitabine versus adjuvant chemotherapy with Cisplatin + 5-Fluorouracil(PX-P vs P-PF)

3. comparing accelerated fractionation versus conventional fractionation (AF vs CF)radiotherapy.

2. secondary objectives include

1. comparing induction chemotherapy with Cisplatin + Capecitabine versus induction chemotherapy with Cisplatin + 5-Fluorouracil(PX-P vs PX-P)

2. Comparing concurrent-adjuvant (CA) versus induction-concurrent (IC) chemotherapy sequence.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 803
• Est. completion date: December 2018
• Est. primary completion date: May 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

• histologically proven nasopharyngeal carcinoma for primary treatment with radical intent

• non-keratinizing or undifferentiated type

• stage III-IVB (by AJCC/UICC 6th edition)

• ECOG Performance status less or equal to 2

• Marrow: WBC >= 4 and platelet >=100

• Renal: creatinine clearance >=60

• Informed consent

Exclusion Criteria:

• Primary treatment with palliative intent

• WHO type I squamous cell carcinoma or adenocarcinoma

• Evidence of distant metastases

• Patient is pregnant or lactating

• Prior malignancy except adequately treated basal cell or squamous cell skin cancer, in-situ cervical cancer or other cancer for which the patient has been disease-free for 5 years

Related Conditions & MeSH terms

• Carcinoma
• Nasopharyngeal Carcinoma

Intervention

Drug:
• Capecitabine
Dose:1000 mg/m2, BD, Day 1-Day 14 Interval: 21 days Cycles: 3 cycles
• Adjuvant chemotherapy using PF (5-Fluorouracil )
Cisplatin 80 mg/m2 IV + 5-Fluorouracil 1000 mg/m2/day IV infusion for 96 hr every 28 days for 3 cycles
• Induction chemotherapy using PF (5-Fluorouracil)
Cisplatin 100 mg/m2 IV + 5-Fluorouracil 1000 mg/m2/day IV infusion for 120 hr every 21 days for 3 cycles

Locations

Country	Name	City	State
China	Cancer Center, Sun Yat Sen University	Guangzhou
China	Department of Clinical Oncology, Pamela Youde Nethersole Eastern Hospital	Hong Kong
China	Department of Clinical Oncology, Prince of Wales Hospital	Hong Kong
China	Department of Clinical Oncology, Princess Margaret Hospital	Hong Kong
China	Department of Clinical Oncology, Queen Elizabeth Hospital	Hong Kong
China	Department of Clinical Oncology, Queen Mary Hospital	Hong Kong
China	Department of Clinical Oncology, Tuen Mun Hospital	Hong Kong

Sponsors (3)

Lead Sponsor	Collaborator
Hong Kong Nasopharyngeal Cancer Study Group Limited	hong Kong Cancer Fund, The Hong Kong Anti-Cancer Society

Country where clinical trial is conducted

China, 

References & Publications (11)

Al-Sarraf M, LeBlanc M, Giri PG, Fu KK, Cooper J, Vuong T, Forastiere AA, Adams G, Sakr WA, Schuller DE, Ensley JF. Chemoradiotherapy versus radiotherapy in patients with advanced nasopharyngeal cancer: phase III randomized Intergroup study 0099. J Clin Oncol. 1998 Apr;16(4):1310-7. — View Citation

Baujat B, Audry H, Bourhis J, Chan AT, Onat H, Chua DT, Kwong DL, Al-Sarraf M, Chi KH, Hareyama M, Leung SF, Thephamongkhol K, Pignon JP; MAC-NPC Collaborative Group. Chemotherapy in locally advanced nasopharyngeal carcinoma: an individual patient data meta-analysis of eight randomized trials and 1753 patients. Int J Radiat Oncol Biol Phys. 2006 Jan 1;64(1):47-56. Review. — View Citation

Chua DT, Sham JS, Au GK. A phase II study of capecitabine in patients with recurrent and metastatic nasopharyngeal carcinoma pretreated with platinum-based chemotherapy. Oral Oncol. 2003 Jun;39(4):361-6. — View Citation

Freedman J, Furberg, C, DeMets D. Fundamentals of clinical trials. Springer-Verlag, NY, 1998.

Greene FL, et al. AJCC Cancer Staging Handbook from the AJCC cancer staging manual, 6th ed. New York: Springer, 2002.

Hoff PM, Ansari R, Batist G, Cox J, Kocha W, Kuperminc M, Maroun J, Walde D, Weaver C, Harrison E, Burger HU, Osterwalder B, Wong AO, Wong R. Comparison of oral capecitabine versus intravenous fluorouracil plus leucovorin as first-line treatment in 605 patients with metastatic colorectal cancer: results of a randomized phase III study. J Clin Oncol. 2001 Apr 15;19(8):2282-92. — View Citation

Le QT, Tate D, Koong A, Gibbs IC, Chang SD, Adler JR, Pinto HA, Terris DJ, Fee WE, Goffinet DR. Improved local control with stereotactic radiosurgical boost in patients with nasopharyngeal carcinoma. Int J Radiat Oncol Biol Phys. 2003 Jul 15;56(4):1046-54. — View Citation

Lee AW, Lau WH, Tung SY, Chua DT, Chappell R, Xu L, Siu L, Sze WM, Leung TW, Sham JS, Ngan RK, Law SC, Yau TK, Au JS, O'Sullivan B, Pang ES, O SK, Au GK, Lau JT; Hong Kong Nasopharyngeal Cancer Study Group. Preliminary results of a randomized study on therapeutic gain by concurrent chemotherapy for regionally-advanced nasopharyngeal carcinoma: NPC-9901 Trial by the Hong Kong Nasopharyngeal Cancer Study Group. J Clin Oncol. 2005 Oct 1;23(28):6966-75. — View Citation

Lee AW, Tung SY, Chan AT, Chappell R, Fu YT, Lu TX, Tan T, Chua DT, O'sullivan B, Xu SL, Pang ES, Sze WM, Leung TW, Kwan WH, Chan PT, Liu XF, Tan EH, Sham JS, Siu L, Lau WH. Preliminary results of a randomized study (NPC-9902 Trial) on therapeutic gain by concurrent chemotherapy and/or accelerated fractionation for locally advanced nasopharyngeal carcinoma. Int J Radiat Oncol Biol Phys. 2006 Sep 1;66(1):142-51. — View Citation

Lee N, Xia P, Quivey JM, Sultanem K, Poon I, Akazawa C, Akazawa P, Weinberg V, Fu KK. Intensity-modulated radiotherapy in the treatment of nasopharyngeal carcinoma: an update of the UCSF experience. Int J Radiat Oncol Biol Phys. 2002 May 1;53(1):12-22. — View Citation

Twelves C, Boyer M, Findlay M, Cassidy J, Weitzel C, Barker C, Osterwalder B, Jamieson C, Hieke K; Xeloda Colorectal Cancer Study Group. Capecitabine (Xeloda) improves medical resource use compared with 5-fluorouracil plus leucovorin in a phase III trial conducted in patients with advanced colorectal carcinoma. Eur J Cancer. 2001 Mar;37(5):597-604. — View Citation

* Note: There are 11 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-Free Survival, defined as the time to treatment failure at any site or death due to any cause, at 5-year.		5 years
Primary	Overall Survival, defined as the time to death due to any cause, at 5-year.		5 years
Secondary	overall Failure-Free Rate, defined as time to failure at any site)		5 years
Secondary	Loco-regional Failure-Free Rate, defined as time to local or nodal failure)		5 years
Secondary	Distant Failure-Free Rate, defined as time to distant failure)		5 years
Secondary	Incidence of chemotherapy toxicity and acute RT toxicity grade > 3		treatment
Secondary	Time to late toxicity (From the date of randomization to the earliest date of late toxicity grade > 3)		5 years