Induction Chemotherapy Followed by Concurrent Radiation With Cetuximab or Cisplatin in Locally Advanced Nasopharyngeal Cancer

Phase II Trial of Docetaxel-Cisplatin Neoadjuvant Chemotherapy Followed by Concurrent Radiotherapy With Cetuximab or Weekly Cisplatin in Locally Advanced Nasopharyngeal Carcinoma

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.

Study Overview

• Status: Unknown
• Conditions: Nasopharyngeal Carcinoma
• Intervention / Treatment: Drug: Cisplatin; Drug: Docetaxel; Radiation: Intensity-modulated radiotherapy; Drug: Cisplatin; Drug: Cetuximab

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.

• Study Type: Interventional
• Enrollment (Actual): 46
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200032
      • Fudan University Shanghai Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: cisplatin-radiotherapy (CRT); The arm receiving docetaxel-cisplatin neoadjuvant chemotherapy followed by concurrent weekly cisplatin and radiotherapy	Drug: Cisplatin; 2 cycles of induction chemotherapy every 3 weeks with cisplatin 80 mg/m2 D1-3; Other Names: Platinol; Drug: Docetaxel; 2 cycles of induction chemotherapy every 3 weeks with docetaxel 75 mg/m2 D1; Other Names: Taxotere; Radiation: Intensity-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; Other Names: IMRT; Drug: Cisplatin; 2 cycles of induction chemotherapy every 3 weeks with cisplatin 80 mg/m2 D1-3, then 6 cycles of concomitant chemotherapy every week with cisplatin 30 mg/m2 D1; Other Names: Platinol
Experimental: cetuximab-radiotherapy (ERT); The arm receiving docetaxel-cisplatin neoadjuvant chemotherapy followed by concurrent cetuximab and radiotherapy	Drug: Cisplatin; 2 cycles of induction chemotherapy every 3 weeks with cisplatin 80 mg/m2 D1-3; Other Names: Platinol; Drug: Docetaxel; 2 cycles of induction chemotherapy every 3 weeks with docetaxel 75 mg/m2 D1; Other Names: Taxotere; Radiation: Intensity-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; Other Names: IMRT; Drug: Cisplatin; 2 cycles of induction chemotherapy every 3 weeks with cisplatin 80 mg/m2 D1-3, then 6 cycles of concomitant chemotherapy every week with cisplatin 30 mg/m2 D1; Other Names: Platinol; Drug: Cetuximab; 400 mg/m2 initial dose before radiation, then 250 mg/m2 weekly during radiation; Other Names: Erbitux

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival	The time from date of randomization until date of first documented disease progression or death from any cause, assessed up to 3 years.	up to 3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	QoL score will be documented on each weekend during the course of radiotherapy	participants will be followed for the duration of hospital stay, an expected average of 6 weeks
Overall survival	The time from date of randomization until date of death due to any cause, assessed up to 3 years.	up to 3 years
Locoregional recurrence-free survival	The time from date of randomization until date of first documented disease recurrence at a locoregional site, assessed up to 3 years.	up to 3 years
Distant metastasis-free survival	The time from date of randomization until date of first documented distant metastasis, assessed up to 3 years.	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
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
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) at 3 months after completion of radiotherapy		At 3 months after completion of radiotherapy

Collaborators and Investigators

• Sponsor: Fudan University
• Investigators: Principal Investigator: Guopei Zhu, M.D., Fudan University

Publications and helpful links

General Publications

• Xu T, Liu Y, Dou S, Li F, Guan X, Zhu G. Weekly cetuximab concurrent with IMRT aggravated radiation-induced oral mucositis in locally advanced nasopharyngeal carcinoma: Results of a randomized phase II study. Oral Oncol. 2015 Sep;51(9):875-9. doi: 10.1016/j.oraloncology.2015.06.008. Epub 2015 Jul 7.

Study record dates

Study Major Dates

• Study Start: August 1, 2010
• Primary Completion (Anticipated): August 1, 2014
• Study Completion (Anticipated): August 1, 2014

Study Registration Dates

• First Submitted: June 5, 2012
• First Submitted That Met QC Criteria: June 6, 2012
• First Posted (Estimate): June 8, 2012

Study Record Updates

• Last Update Posted (Estimate): June 8, 2012
• Last Update Submitted That Met QC Criteria: June 6, 2012
• Last Verified: June 1, 2012

More Information

Terms related to this study

• Keywords: Cetuximab; Locally advanced; Nasopharyngeal carcinoma; Intensity-modulated radiotherapy; Weekly cisplatin chemotherapy
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Head and Neck Neoplasms; Nasopharyngeal Diseases; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases; Nasopharyngeal Neoplasms; Carcinoma; Nasopharyngeal Carcinoma; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Immunological; Docetaxel; Cisplatin; Cetuximab
• Other Study ID Numbers: HN201002