Cisplatin-based and Carboplatin-based Chemoradiation in Locoregionally Advanced Nasopharyngeal Carcinoma

Official title

Intensity-modulated Radiation Therapy Combined With Cisplatin-based or Carboplatin-based Chemotherapy in Locoregionally Advanced Nasopharyngeal Carcinoma：: A Phase 3 Trial

Overview

The purpose of this study is to compare cisplatin-based with carboplatin-based chemoradiotherapy in patients with locoregionally advanced nasopharyngeal carcinoma (NPC), in order to confirm the value of carboplatin-based chemoradiotherapy in NPC patients.

Detailed description

Patients presented with non-keratinizing NPC and stage T3-4NxM0/TxN2-3M0 are randomly assigned to receive cisplatin-based (control arm) with carboplatin-based (investigational arm) chemoradiotherapy. Patients in the investigational arm receive docetaxel (75mg/m2 on day 1), carboplatin (AUC 4 on day 1) every three weeks for two cycles before the radiotherapy, and then receive radical radiotherapy and carboplatin (AUC 5 on day 1) every three weeks for three cycles during radiotherapy. Patients in the control arm receive docetaxel (75mg/m2 on day 1), cisplatin (75mg/m2 on day 1) every three weeks for two cycles before the radiotherapy, and then receive radical radiotherapy and cisplatin (100mg/m2 on day 1) every three weeks for three cycles during radiotherapy. Patients are stratified according to stage. The primary end point is overall survival (OS). Secondary end points include failure-free survival (FFS), distant failure-free survival (D-FFS), locoregional failure-free survival (LR-FFS), initial response rates after treatments and toxic effects. All efficacy analyses are conducted in the intention-to-treat population; the safety population include only patients who receive their randomly assigned treatment.

Interventions

• Drug Docetaxel,Carboplatin
  Patients receive docetaxel (75mg/m2 on day 1), carboplatin (AUC 4 on day 1) every three weeks for two cycles before the radiotherapy.
• Drug Docetaxel,Cisplatin
  Patients receive docetaxel (75mg/m2 on day 1), cisplatin (75mg/m2 on day 1) every three weeks for two cycles before the radiotherapy.
• Radiation Carboplatin-based concurrent chemoradiotherapy
  Patients receive radical radiotherapy and carboplatin (AUC 5) every three weeks for three cycles during radiotherapy.
• Radiation Cisplatin-based concurrent chemoradiotherapy
  Patients receive radical radiotherapy and cisplatin (100mg/m2) every three weeks for three cycles during radiotherapy.

Primary outcome measures

• Failure-free survival [Time frame: 3-year]

Secondary outcome measures (5)

• Locoregional failure-free survival [Time frame: 3-year]
• Distant failure-free survival [Time frame: 3-year]
• The initial response rates after treatments [Time frame: A week after completion of the last cycle of induction chemotherapy and 16 weeks after completion of radiotherapy.]
• Toxic effects [Time frame: 3-year]
• Overall survival [Time frame: 3-year]

Eligibility criteria

Inclusion criteria

• Patients with newly histologically confirmed non-keratinizing (according to World Health Organization (WHO) histologically type).
• Tumor staged as T3-4Nx/TxN2-3 (according to the 8th American Joint Commission on Cancer edition).
• No evidence of distant metastasis (M0).
• Satisfactory performance status: Karnofsky scale (KPS) > 70.
• 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 or basaloid squamous cell carcinoma.
• Age ≥65 years or <18 years.
• Treatment with palliative intent.
• Prior malignancy except adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer.
• Pregnancy or lactation.
• History of previous radiotherapy (except for non-melanomatous skin cancers outside intended RT treatment volume).
• Prior chemotherapy or surgery (except diagnostic) to primary tumor or nodes.
• 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Single blind

Primary purpose

Treatment

Study locations

China · 1 center

• Southern medical university — Guangzhou

Publications

• Haddad RI, Shin DM. Recent advances in head and neck cancer. N Engl J Med. 2008 Sep 11;359(11):1143-54. doi: 10.1056/NEJMra0707975. No abstract available. PMID 18784104
• Guan J, Zhang Y, Li Q, Zhang Y, Li L, Chen M, Xiao N, Chen L. A meta-analysis of weekly cisplatin versus three weekly cisplatin chemotherapy plus concurrent radiotherapy (CRT) for advanced head and neck cancer (HNC). Oncotarget. 2016 Oct 25;7(43):70185-70193. doi: 10.18632/oncotarget.11824. PMID 27602493
• Hashibe M, Brennan P, Chuang SC, Boccia S, Castellsague X, Chen C, Curado MP, Dal Maso L, Daudt AW, Fabianova E, Fernandez L, Wunsch-Filho V, Franceschi S, Hayes RB, Herrero R, Kelsey K, Koifman S, La Vecchia C, Lazarus P, Levi F, Lence JJ, Mates D, Matos E, Menezes A, McClean MD, Muscat J, Eluf-Neto J, Olshan AF, Purdue M, Rudnai P, Schwartz SM, Smith E, Sturgis EM, Szeszenia-Dabrowska N, Talamin PMID 19190158
• Blot WJ, McLaughlin JK, Winn DM, Austin DF, Greenberg RS, Preston-Martin S, Bernstein L, Schoenberg JB, Stemhagen A, Fraumeni JF Jr. Smoking and drinking in relation to oral and pharyngeal cancer. Cancer Res. 1988 Jun 1;48(11):3282-7. PMID 3365707
• Chang ET, Adami HO. The enigmatic epidemiology of nasopharyngeal carcinoma. Cancer Epidemiol Biomarkers Prev. 2006 Oct;15(10):1765-77. doi: 10.1158/1055-9965.EPI-06-0353. PMID 17035381
• Klein G. Nasopharyngeal carcinoma (NPC) is an enigmatic tumor. Semin Cancer Biol. 2002 Dec;12(6):415-8. doi: 10.1016/s1044579x02000834. No abstract available. PMID 12450726
• Buell P. The effect of migration on the risk of nasopharyngeal cancer among Chinese. Cancer Res. 1974 May;34(5):1189-91. No abstract available. PMID 4842361
• Ozer E, Grecula JC, Agrawal A, Rhoades CA, Young DC, Schuller DE. Long-term results of a multimodal intensification regimen for previously untreated advanced resectable squamous cell cancer of the oral cavity, oropharynx, or hypopharynx. Laryngoscope. 2006 Apr;116(4):607-12. doi: 10.1097/01.mlg.0000208340.42071.f9. PMID 16585867

Identifiers

NCT: NCT03919552 · NFEC-2018-013

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗