A Trial On 4 Cycles Of Neoadjuvant Chemotherapy Plus Concurrent Chemoradiation In N2-3 Nasopharyngeal Carcinoma

August 24, 2021 updated by: Yuan-hong Gao, Sun Yat-sen University

4 Cycles Of Neoadjuvant Chemotherapy Plus Concurrent Chemoradiation Versus Concurrent Chemoradiation Alone In Patients With Stage N2-3 Nasopharyngeal Carcinoma: A Phase 3 Multicenter Randomised Controlled Trial

The standard treatment strategy of locally advanced nasopharyngeal carcinoma (NPC) nowadays is concurrent chemoradiation (CCRT) based on intensity-modulated radiation therapy (IMRT). However, distant metastasis remains the major cause of treatment failure, especially in patients with T1-4N2-3M0 diseases (N2-3 NPC). The investigators inferred that it was more appropriate to consider N2-3 NPC as a systemic disease instead of a local disease. NACT of sufficient intensity such as 4 cycles might be effective enough for control of the pre-existing micrometastases. Therefore, the objective of this phase 3 multicenter randomized controlled trial is to make a comparison between NACT of 4 cycles plus CCRT based on IMRT and CCRT alone in N2-3 NPC on distant metastasis, survival and adverse reaction.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

The standard treatment strategy of locally advanced nasopharyngeal carcinoma (NPC) nowadays is concurrent chemoradiation (CCRT), which is based on intensity-modulated radiation therapy (IMRT) and achieves a satisfactory local-regional control and a 5-year overall survival (OS) of 83.0%. However, distant metastasis remains the major cause of treatment failure, especially in patients with T1-4N2-3M0 diseases (N2-3 NPC). The distant metastasis reaches 35-48% after CCRT alone.

To decrease distant metastasis of locally advanced NPC so as to improve survival, approaches on modifying timing of chemotherapy have been made to mainly 2 types: one was CCRT plus adjuvant chemotherapy (ACT), the other was neoadjuvant chemotherapy (NACT) plus CCRT. It was proved that CCRT plus ACT could not improve survival of locally advanced NPC further. Some clinical trials indicated that locally advanced NPC patients with 2-3 cycles of NACT plus CCRT had a better survival than those with CCRT alone though the roles of NACT remain controversial.

It is known that N stage is by far the most significant predicting factor of metastasis risk for NPC. N2-3 NPC was also proved to have a quite great risk of distant failure. 51.4% of distant metastases happened within 1 year after CCRT. The investigators inferred that subclinical micrometastases were already present before treatment starting. Hence, it was more appropriate to consider N2-3 NPC as a systemic disease instead of a local disease. NACT of sufficient intensity such as 4 cycles might be effective enough for control of the pre-existing micrometastases.

Therefore, this phase 3 multicenter randomized controlled trial is conducted to enroll 144 patients with N2-3 NPC. After stratification by N stage, the patients will be allocated into 2 treatment groups randomly at a ratio of 1:1 and applied with different treatment strategies to make a comparison between NACT of 4 cycles plus CCRT based on IMRT and CCRT alone in N2-3 NPC on distant metastasis, survival and adverse reaction.

Study Type

Interventional

Enrollment (Anticipated)

192

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • China
    • Guangdong
      • Guangzhou, Guangdong, China, 510060
        • Recruiting
        • Sun Yat-sen University Cancer Center
        • Contact:
        • Contact:
        • Principal Investigator:
          • Yuan-hong Gao, M.D
        • Sub-Investigator:
          • Li-xia Lu, M.D
        • Sub-Investigator:
          • Qing Liu, Ph.D
        • Sub-Investigator:
          • Hui Chang, M.D
        • Sub-Investigator:
          • Xin-hua Jiang, M.D
        • Sub-Investigator:
          • Wei-wei Xiao, M.D
        • Sub-Investigator:
          • Qi-wen Li, M.D
        • Sub-Investigator:
          • Lu-ning Zhang, M.D
        • Sub-Investigator:
          • Xin Yu, M.D
      • Guangzhou, Guangdong, China, 510030
        • Recruiting
        • Cancer Center of Guangzhou Medical University
        • Contact:
          • Tong-chong Zhou, M.D
          • Phone Number: +86-13808841276
          • Email: noveaie@163.com
        • Contact:
        • Principal Investigator:
          • Tong-chong Zhou, M.D
        • Sub-Investigator:
          • Hai-hua Peng, M.D
      • Guangzhou, Guangdong, China, 510060
        • Recruiting
        • First Affiliated Hospital of Sun Yat-sen University
        • Contact:
        • Contact:
        • Principal Investigator:
          • Bi-Xiu Wen, M.D
        • Sub-Investigator:
          • Cheng-tao Wang, M.D
      • Shenzhen, Guangdong, China, 518020
        • Recruiting
        • Shenzhen People's Hospital
        • Contact:
        • Contact:
        • Principal Investigator:
          • Ya-jie Liu, M.D
        • Sub-Investigator:
          • Shi-hai Wu, M.D

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

No older than 70 years (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Patients with pathological diagnosis of nasopharyngeal carcinoma
  • Union Internationale Contre le Cancer/American Joint Cancer Committee (UICC/AJCC) 2010 Stage T1-4 N2-3 M0 through magnetic resonance imaging of head and neck, whole-body bone scan and thoracoabdominal computed tomography
  • Male or female with age no older than 70 years old
  • Karnofsky Performance Scores ≥ 80
  • Expected survival ≥ 3 months

Exclusion Criteria:

  • Patients with distant metastasis before or during radiotherapy
  • Severe dysfunction of heart, lung, liver, kidney or hematopoietic system
  • Severe neurological, mental or endocrine diseases
  • History of other malignancies
  • Prior chemotherapy, radiotherapy or application of monoclonal antibodies
  • Patients participated in clinical trials of other drugs within last 3 months
  • Pregnant or lactating women
  • Those who are considered by the researchers unsuitable to participate

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: CCRT group (Group A)
Patients who are allocated into in this group will be treated with concurrent chemoradiation (CCRT).
Radiation: Concurrent chemoradiation (CCRT)

The technology of radiotherapy is intensity-modulated radiation therapy (IMRT). A total dose of 66-72Gy is given to gross tumor of nasopharynx (GTVnx), 60-70Gy to positive neck lymph nodes (GTVnd), 60Gy to high-risk region (CTV1), and 50-54Gy to prophylactic irradiation region (CTV2).

The regimen of concurrent chemotherapy is single-agent cisplatin 40mg/m2 weekly.
Experimental: NACT-CCRT group (Group B)
Patients who are allocated into in this group will be treated with 4 cycles of neoadjuvant chemotherapy (NACT, docetaxel plus cisplatin) followed by CCRT.
Radiation: Concurrent chemoradiation (CCRT)

The technology of radiotherapy is intensity-modulated radiation therapy (IMRT). A total dose of 66-72Gy is given to gross tumor of nasopharynx (GTVnx), 60-70Gy to positive neck lymph nodes (GTVnd), 60Gy to high-risk region (CTV1), and 50-54Gy to prophylactic irradiation region (CTV2).

The regimen of concurrent chemotherapy is single-agent cisplatin 40mg/m2 weekly.

Drug: Docetaxel (DOC)
Neoadjuvant chemotherapy (NACT) is administrated every 3 weeks with the regimen comprised of docetaxel plus cisplatin. A total of 4 cycles of NACT is applied. Docetaxel is given at a dose of 75mg/m2 on the first day of every cycle.
Other Names:
  • Docetaxel Injection
Drug: Cisplatin (DDP)
Neoadjuvant chemotherapy (NACT) is administrated every 3 weeks with the regimen comprised of docetaxel plus cisplatin. A total of 4 cycles of NACT is applied. Cisplatin is given at a dose of 75mg/m2 on the first day of every cycle.
Other Names:
  • Cisplatin Injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
5-year overall survival (5y-OS)
Time Frame: 5 years after the date of pathologic diagnosis
Percentage of patients in a treatment group who are alive for a 5-year period of follow-up after the date of pathologic diagnosis
5 years after the date of pathologic diagnosis
5-year distant-metastasis-free survival (5y-MFS)
Time Frame: 5 years after the date of pathologic diagnosis
Percentage of patients in a treatment group who are alive without distant metastasis for a 5-year period of follow-up after the date of pathologic diagnosis
5 years after the date of pathologic diagnosis

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
5-year local-relapse-free survival (5y-RFS)
Time Frame: 5 years after the date of pathologic diagnosis
Percentage of patients in a treatment group who are alive without local recurrence for a 5-year period of follow-up after the date of pathologic diagnosis
5 years after the date of pathologic diagnosis
5-year disease-free survival (5y-DFS)
Time Frame: 5 years after the date of pathologic diagnosis
Percentage of patients in a treatment group who are alive without disease-related events (local recurrence, distant metastasis) for a 5-year period of follow-up after the date of pathologic diagnosis
5 years after the date of pathologic diagnosis
Incidence of grade 3/4 adverse event
Time Frame: Once a week during therapy, up to 7 weeks (Group A) or 19 weeks (Group B)
Incidence of patients in a treatment group who manifest a specific adverse event (such as myelosuppression) of grade 3/4. Incidence is calculated for each adverse event respectively and severity is evaluated on basis of Common Terminology Criteria for Adverse Events (CTCAE) 4.0 criteria.
Once a week during therapy, up to 7 weeks (Group A) or 19 weeks (Group B)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sun Yat-sen University

Investigators

  • Principal Investigator: Yuan-hong Gao, M.D, Sun Yat-sen University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 1, 2015

Primary Completion (Anticipated)

December 1, 2024

Study Completion (Anticipated)

December 1, 2024

Study Registration Dates

First Submitted

July 24, 2015

First Submitted That Met QC Criteria

July 27, 2015

First Posted (Estimate)

July 30, 2015

Study Record Updates

Last Update Posted (Actual)

August 30, 2021

Last Update Submitted That Met QC Criteria

August 24, 2021

Last Verified

August 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NACT4-NPC-5010

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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