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

NCT00379262 | Completed Phase 3 DMC

• 1 other identifier: NPC-0501 Trial
• Study Type: interventional
• Target: 803
• Locations: 1 country
• Sites: 7

Brief Summary

The objectives of this clinical study are threefold:

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

Conditions

Nasopharyngeal Carcinoma

Keywords

Nasopharyngeal Carcinoma; Chemoradiotherapy; Accelerated Fractionation

Outcome Measures

Primary Outcomes (2)

• Progression-Free Survival, defined as the time to treatment failure at any site or death due to any cause, at 5-year.

  5 years

• Overall Survival, defined as the time to death due to any cause, at 5-year.

  5 years

Secondary Outcomes (5)

• overall Failure-Free Rate, defined as time to failure at any site)

  5 years

• Loco-regional Failure-Free Rate, defined as time to local or nodal failure)

  5 years

• Distant Failure-Free Rate, defined as time to distant failure)

  5 years

• Incidence of chemotherapy toxicity and acute RT toxicity grade > 3

  treatment

• Time to late toxicity (From the date of randomization to the earliest date of late toxicity grade > 3)

  5 years

Study Arms (6)

1A

EXPERIMENTAL

Concurrent-Adjuvant CRT using P-PF regimen and conventional fractionation radiotherapy

Drug: Adjuvant chemotherapy using PF (5-Fluorouracil )

1B

EXPERIMENTAL

Concurrent-Adjuvant CRT using P-PF regimen and accelerated fractionation radiotherapy

Drug: Adjuvant chemotherapy using PF (5-Fluorouracil )

2A

EXPERIMENTAL

Induction-Concurrent CRT using PF-P regimen and conventional fractionation radiotherapy

Drug: Induction chemotherapy using PF (5-Fluorouracil)

2B

EXPERIMENTAL

Induction-Concurrent CRT using PF-P regimen and accelerated fractionation radiotherapy

Drug: Induction chemotherapy using PF (5-Fluorouracil)

3A

EXPERIMENTAL

Induction-Concurrent CRT using PX-P regimen and conventional fractionation radiotherapy

Drug: Capecitabine

3B

EXPERIMENTAL

Induction-Concurrent CRT using PX-P regimen and accelerated fractionation radiotherapy

Drug: Capecitabine

Interventions

Capecitabine DRUG

Dose:1000 mg/m2, BD, Day 1-Day 14 Interval: 21 days Cycles: 3 cycles

Also known as: Xeloda

3A; 3B

Adjuvant chemotherapy using PF (5-Fluorouracil ) DRUG

Cisplatin 80 mg/m2 IV + 5-Fluorouracil 1000 mg/m2/day IV infusion for 96 hr every 28 days for 3 cycles

1A; 1B

Induction chemotherapy using PF (5-Fluorouracil) DRUG

Cisplatin 100 mg/m2 IV + 5-Fluorouracil 1000 mg/m2/day IV infusion for 120 hr every 21 days for 3 cycles

2A; 2B

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Hong Kong Nasopharyngeal Cancer Study Group Limited: lead
• The Hong Kong Anti-Cancer Society: collaborator
• hong Kong Cancer Fund: collaborator

Study Sites (7)

Cancer Center, Sun Yat Sen University

Guangzhou, China

Location

Department of Clinical Oncology, Pamela Youde Nethersole Eastern Hospital

Hong Kong, China

Location

Department of Clinical Oncology, Prince of Wales Hospital

Hong Kong, China

Location

Department of Clinical Oncology, Princess Margaret Hospital

Hong Kong, China

Location

Department of Clinical Oncology, Queen Elizabeth Hospital

Hong Kong, China

Location

Department of Clinical Oncology, Queen Mary Hospital

Hong Kong, China

Location

Department of Clinical Oncology, Tuen Mun Hospital

Hong Kong, China

Location

Related 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. doi: 10.1200/JCO.1998.16.4.1310.

  PMID: 9552031 BACKGROUND

• 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. doi: 10.1200/JCO.2004.00.7542.

  PMID: 16192584 BACKGROUND

• 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. doi: 10.1016/s0360-3016(02)02724-4.

  PMID: 12007936 BACKGROUND

• 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. doi: 10.1016/s0360-3016(03)00117-2.

  PMID: 12829140 BACKGROUND

• 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. doi: 10.1016/j.ijrobp.2005.06.037.

  PMID: 16377415 BACKGROUND

• 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. doi: 10.1200/JCO.2001.19.8.2282.

  PMID: 11304782 BACKGROUND

• 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. doi: 10.1016/s0959-8049(00)00444-5.

  PMID: 11290435 BACKGROUND

• 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. doi: 10.1016/s1368-8375(02)00120-3.

  PMID: 12676255 BACKGROUND

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

  BACKGROUND

• 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. doi: 10.1016/j.ijrobp.2006.03.054.

  PMID: 16904519 BACKGROUND

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

  BACKGROUND

MeSH Terms

Conditions

Nasopharyngeal Carcinoma

Interventions

Capecitabine; Fluorouracil

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Nasopharyngeal Neoplasms; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Head and Neck Neoplasms; Neoplasms by Site; Nasopharyngeal Diseases; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases

Intervention Hierarchy (Ancestors)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Anne W.M. Lee, F.R.C.R.

  Department of Clinical Oncology, Pamela Youde Nethersole Eastern Hospital, Hong Kong

  PRINCIPAL INVESTIGATOR

• Roger K.C. Ngan, F.R.C.R

  Department of Clinical Oncology, Quen Elizabeth Hospital, Hong Kong

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Consultant, Dept of Clinical Oncology, PYNEH

Study Record Dates

• First Submitted: September 20, 2006
• First Posted: September 21, 2006
• Study Start: September 1, 2006
• Primary Completion: May 1, 2017
• Study Completion: December 1, 2018
• Last Updated: August 7, 2019

Record last verified: 2019-08

Locations

CN (7)