A Multicenter, Prospective, Phase III Randomized Controlled Clinical Study for the Treatment of N2-3 Nasopharyngeal Carcinoma Patients

A Multicenter, Prospective, Phase III Randomized Controlled Clinical Study Comparing 4 Cycles of Neoadjuvant Chemotherapy Combined With Radiotherapy Versus 3cycles of Neoadjuvant Chemotherapy Combined With Concurrent Chemoradiotherapy for the Treatment of N2-3 Nasopharyngeal Carcinoma

At the initial diagnosis of locally advanced nasopharyngeal carcinoma, a considerable proportion of patients have developed distant metastasis, forming subclinical lesions. Nowadays, with the advent of intensity modulated radiotherapy, the local-regional area is under well controlled. However, distant metastasis is still the main cause of failure in treatment of stage N2-3 nasopharyngeal carcinoma.The severe toxicity of synchronous chemotherapy and the dose intensity of single drug is not enough to effectively control existing subclinical lesions. Neoadjuvant chemotherapy with sufficient intensity (four cycles) can possible effectively kill subclinical lesions prior to the initiation of concurrent chemoradiotherapy, thereby reducing distant metastasis of stage N2-3 nasopharyngeal carcinoma. Meanwhile, four cycles of chemotherapy have been shown to be well tolerated in other tumors. In conclusion, 4-cycle neoadjuvant chemotherapy in combination with radiotherapy is expected to further control the distant metastasis rate of N2-3 nasopharyngeal carcinoma and improve the survival rate.

Study Overview

• Status: Unknown
• Conditions: Nasopharyngeal Carcinoma; Neoadjuvant Chemotherapy
• Intervention / Treatment: Drug: 4 cycles of Neoadjuvant Chemotherapy With Definitive Radiotherapy; Drug: 3 cycles of Neoadjuvant Chemotherapy With concurrent chemoradiotherapy

• Study Type: Interventional
• Enrollment (Anticipated): 246
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Qichun Wei; Phone Number: 0571-87783522; Email: qichun_wei@zju.edu.cn
• Study Contact Backup: Name: Jing Xu; Phone Number: 0571-87783522; Email: shanyefengxu@163.com

Study Locations

• China
  • Fujian
    • Fuzhou, Fujian, China, 350001
      • Not yet recruiting
      • Fujian Medical University Union Hospital
      • Contact: Benhua Xu
  • Guangdong
    • Guandong, Guangdong, China, 510060
      • Not yet recruiting
      • Cancer Prevention and Treatment Center, Sun Yat-sen University
      • Contact: Yuanhong Gao
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310009
      • Not yet recruiting
      • The first affiliated hospital, college of medicinle, Zhejiang University
      • Contact: Senxiang Yan
    • Hangzhou, Zhejiang, China, 310009
      • Not yet recruiting
      • Zhejiang Cancer hospital
      • Contact: Xiaozhong Chen
    • Hangzhou, Zhejiang, China, 310009
      • Not yet recruiting
      • Zhejiang Provincial People's Hospital
      • Contact: Yongshi Jia
    • Hangzhou, Zhejiang, China, 310058
      • Recruiting
      • 2nd Affiliated Hospital, School of Medicine, Zhejiang University, China
      • Contact: Zexin Chen; Phone Number: +86 0571 87783759; Email: keyanlunli_zheer@163.com
    • Hangzhou, Zhejiang, China, 311200
      • Not yet recruiting
      • Zhejiang Xiaoshan Hospital
      • Contact: Guoping Han
    • Jinhua, Zhejiang, China, 321000
      • Not yet recruiting
      • Jinhua Central Hospital
      • Contact: Wangyuan Hu
    • Lishui, Zhejiang, China, 323000
      • Not yet recruiting
      • Lishui City Central Hospital
      • Contact: Dexi Du
    • Ningbo, Zhejiang, China, 315000
      • Not yet recruiting
      • Ningbo Yinzhou People's Hospital
      • Contact: Jun Chen
    • Ningbo, Zhejiang, China, 315010
      • Not yet recruiting
      • Ningbo No.2 Hospital
      • Contact: Chuangzhou Rao
    • Quzhou, Zhejiang, China, 324000
      • Not yet recruiting
      • People's Hospital of Quzhou
      • Contact: Huijuan He

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. Non-keratinizing nasopharyngeal carcinoma diagnosed by pathology;
2. According to the UICC/AJCC eighth edition staging criteria, clinical staging was T1-4N2 -3M0 (stage N2-3 nasopharyngeal carcinoma);
3. Patients who have not received disease-related anti-tumor system therapy;
4. Age 18~70 years;
5. Perfect liver and kidney function: total bilirubin ≤1.5 times the upper limit of normal value (ULN); AST and ALT≤2.5 ULN; Alkaline phosphatase ≤2.5 ULN; Creatinine clearance rate ≥80 mL/min;
6. Complete blood system function: neutrophil count (ANC) ≥2×109/L, platelet count ≥100×109/L and hemoglobin ≥9 g/dL;
7. Cartesian score ≥70; or ECOG PS 0 or 1
8. Prior to enrollment, the patients must undergo nasopharynx + neck MRI, chest + upper abdomen CT, ECT and other examinations of the whole body bone.
9. Sign the informed consent.

Exclusion Criteria:

1. Patients with distant metastases were identified at the time of diagnosis;
2. Patients with severe medical complications, severe organ (heart, lung) dysfunction, or neuropsychiatric disorders at the time of diagnosis;
3. Previous cases of other malignancies;Complicated with other malignant tumors;Except for cured basal cell carcinoma of the skin or squamous cell carcinoma of the skin or carcinoma in situ of any other site;
4. Use any other investigational drug or participate in another clinical trial with therapeutic intent within 3 months prior to enrollment;
5. A woman who is pregnant or lactating;
6. Known active HIV or HBV, HCV infection;
7. Known to be allergic to drugs that may be used;
8. The researchers did not consider participants to be eligible for this study.

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
Experimental: 4 Cycles of Neoadjuvant Chemotherapy With Radiotherapy; Four cycles of neoadjuvant chemotherapy combined with radical radiotherapy	Drug: 4 cycles of Neoadjuvant Chemotherapy With Definitive Radiotherapy; 4 Cycles of Neoadjuvant Chemotherapy With Definitive Radiotherapy, instead of Concurrent Chemoradiotherapy
Active Comparator: 3cycles of Neoadjuvant Chemotherapy With chemoradiotherapy; 3 cycles of Neoadjuvant Chemotherapy Combined With Concurrent Chemoradiotherapy	Drug: 3 cycles of Neoadjuvant Chemotherapy With concurrent chemoradiotherapy; 3 cycles of Neoadjuvant Chemotherapy With concurrent chemoradiotherapy, instead of definitive radiotherapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
5-year overall survival	the duration between the date of diagnosed and date of patient death	5 years
5-year metastatic free survival	the duration between the date of diagnosed and date of metastasis	5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
5-year disease-free survival	the duration between the date of diagnosed and date of related disease	5 years
5-year recurrence-free survival	the duration between the date of diagnosed and date of recurrence	5 years
Safety (incidence of grade 3/4 adverse reactions)	treatment related toxic effects	5 years

Collaborators and Investigators

• Sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University
• Investigators: Study Chair: Qichun Wei, 2nd Affiliated Hospital, School of Medicine, Zhejiang University, China

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2019
• Primary Completion (Anticipated): June 30, 2022
• Study Completion (Anticipated): December 31, 2022

Study Registration Dates

• First Submitted: August 13, 2019
• First Submitted That Met QC Criteria: August 16, 2019
• First Posted (Actual): August 19, 2019

Study Record Updates

• Last Update Posted (Actual): May 12, 2020
• Last Update Submitted That Met QC Criteria: May 10, 2020
• Last Verified: August 1, 2019

More Information

Terms related to this study

• Keywords: Neoadjuvant Chemotherapy; Nasopharyngeal Carcinoma; Concurrent Chemoradiotherapy
• 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
• Other Study ID Numbers: SAHZhejiangU-2019-009

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No