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

Nasopharyngeal Carcinoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02512315
• Other study ID #: NACT4-NPC-5010
• Status: Recruiting
• Phase: Phase 3
• Start date: August 2015
• Est. completion date: December 2024

Study information

• Verified date: August 2021
• Source: Sun Yat-sen University
• Contact: Yuan-hong Gao, M.D
• Phone: +86-13560182168
• Email: gaoyh[@]sysucc.org.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 192
• Est. completion date: December 2024
• Est. primary completion date: December 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma
• Nasopharyngeal Carcinoma

Intervention

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.
• 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.

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.

Locations

Country	Name	City	State
China	Cancer Center of Guangzhou Medical University	Guangzhou	Guangdong
China	First Affiliated Hospital of Sun Yat-sen University	Guangzhou	Guangdong
China	Sun Yat-sen University Cancer Center	Guangzhou	Guangdong
China	Shenzhen People's Hospital	Shenzhen	Guangdong

Sponsors (1)

Lead Sponsor	Collaborator
Sun Yat-sen University

Country where clinical trial is conducted

China, 

References & Publications (17)

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* Note: There are 17 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	5-year overall survival (5y-OS)	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
Primary	5-year distant-metastasis-free survival (5y-MFS)	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	5-year local-relapse-free survival (5y-RFS)	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
Secondary	5-year disease-free survival (5y-DFS)	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
Secondary	Incidence of grade 3/4 adverse event	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)