Nasopharyngeal Carcinoma
Conditions
Keywords
Nasopharyngeal carcinoma, Locally advanced, Cetuximab, Weekly cisplatin chemotherapy, Intensity-modulated radiotherapy
Brief summary
The purpose of this study is to compare the efficacy and toxicity of docetaxel-cisplatin neoadjuvant chemotherapy followed by concurrent radiotherapy with cetuximab or weekly cisplatin in locally advanced nasopharyngeal carcinoma.
Detailed description
Although concurrent chemoradiation is the standard treatment modality for locally advanced nasopharyngeal carcinoma (NPC), high incidences of distant metastases and severe treatment related toxicities have become an obstacle to be overcome. A phase Ⅱ study conducted by Hui et al. showed that neoadjuvant docetaxel-cisplatin (TP) chemotherapy followed by concurrent chemoradiotherapy was superior to the standard concomitant chemoradiation in terms of the 3-year OS without significantly exacerbating the acute toxicities. Moreover, Bonner et al. demonstrated that RT with concurrent Cetuximab significantly improved the 5-year OS and did not increase the treatment induced toxicities when compared with RT alone. Therefore, we initiated this study to compare the efficacy and toxicity of the two regimens, neoadjuvant chemotherapy followed by concurrent radiotherapy with cetuximab or weekly cisplatin for locally advanced NPC.
Interventions
DRUGCetuximab
400 mg/m2 initial dose before radiation, then 250 mg/m2 weekly during radiation
DRUGCisplatin
2 cycles of induction chemotherapy every 3 weeks with cisplatin 80 mg/m2 D1-3
DRUGDocetaxel
2 cycles of induction chemotherapy every 3 weeks with docetaxel 75 mg/m2 D1
RADIATIONIntensity-modulated radiotherapy
a total dose of 66-70.4Gy in 30-32 fractions over 6-6.5 weeks planned to be delivered to the PTV of gross tumor
Sponsors
Fudan University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
1. Histopathologically proven nasopharyngeal carcinoma (WHO type 2 or 3) 2. Stage Ⅲ-ⅣB disease (AJCC/UICC 2009) 3. ECOG performance status of 0-1 4. Life expectancy of more than 6 months 5. Signed written informed consent 6. Adequate organ function including the following: * Absolute neutrophil count (ANC) \>= 1.5 \* 109/l * Platelets count \>= 100 \* 109/l * Hemoglobin \>= 10 g/dl * AST and ALT \<= 2.5 times institutional upper limit of normal (ULN) * Total bilirubin \<= 1.5 times institutional ULN * Creatinine clearance \>= 50 ml/min * Serum creatine \<= 1 times ULN
Exclusion criteria
1. Evidence of distant metastasis 2. Prior chemotherapy or anti-cancer biologic therapy for any type of cancer, or prior radiotherapy to the head and neck region 3. Other previous or concomitant cancer, except for in situ cervical cancer and cutaneous basal cell carcinoma 4. Pregnant or breast-feeding females, or females and males of childbearing potential not taking adequate contraceptive measures 5. Presence of an uncontrolled concomitant illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free survival | up to 3 years | The time from date of randomization until date of first documented disease progression or death from any cause, assessed up to 3 years. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Locoregional recurrence-free survival | up to 3 years | The time from date of randomization until date of first documented disease recurrence at a locoregional site, assessed up to 3 years. |
| Distant metastasis-free survival | up to 3 years | The time from date of randomization until date of first documented distant metastasis, assessed up to 3 years. |
| Number of participants with hematologic toxicity events occurred during two cycles of neoadjuvant chemotherapy according to CTCAE v4.0 | 1, 2, 3 weeks post-dose | — |
| Overall survival | up to 3 years | The time from date of randomization until date of death due to any cause, assessed up to 3 years. |
| Number of participants with late toxicities (hematologic toxicity events, dysphagia, acne-like rash) occurred from 3 months after completion of radiotherapy to last follow-up visit according to CTCAE v4.0 | Every 3 months during the first 2 years, then every 6 months during year 3 after completion of radiotherapy | — |
| Score of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Head and Neck Core 35 (EORTC QLQ-HN35) during the concurrent treatment | participants will be followed for the duration of hospital stay, an expected average of 6 weeks | QoL score will be documented on each weekend during the course of radiotherapy |
| Score of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Head and Neck Core 35 (EORTC QLQ-HN35) at 3 months after completion of radiotherapy | At 3 months after completion of radiotherapy | — |
| Number of participants with acute toxicities (hematologic toxicity events, oral mucositis, acne-like rash) occurred during the concurrent treatment according to CTCAE v4.0 | participants will be followed for the duration of hospital stay, an expected average of 6 weeks | — |
Countries
China
Outcome results
None listed