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

NCT ID: NCT02512315

Last Updated: 2021-08-30

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE3

Total Enrollment

192 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-08-31

Study Completion Date

2024-12-31

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Nasopharyngeal Carcinoma

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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CCRT group (Group A)

Patients who are allocated into in this group will be treated with concurrent chemoradiation (CCRT).

Group Type ACTIVE_COMPARATOR

Concurrent chemoradiation (CCRT)

Intervention Type RADIATION

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.

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.

Group Type EXPERIMENTAL

Docetaxel (DOC)

Intervention Type DRUG

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)

Intervention Type DRUG

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.

Concurrent chemoradiation (CCRT)

Intervention Type RADIATION

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.

Interventions

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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.

Intervention Type 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.

Intervention Type DRUG

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.

Intervention Type RADIATION

Other Intervention Names

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Docetaxel Injection Cisplatin Injection

Eligibility Criteria

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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
Maximum Eligible Age

70 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Sun Yat-sen University

OTHER

Sponsor Role lead

Responsible Party

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Yuan-hong Gao

Deputy Director of Department of Radiation Oncology, Sun Yat-sen University Cancer Center

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Yuan-hong Gao, M.D

Role: PRINCIPAL_INVESTIGATOR

Sun Yat-sen University

Locations

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Cancer Center of Guangzhou Medical University

Guangzhou, Guangdong, China

Site Status RECRUITING

First Affiliated Hospital of Sun Yat-sen University

Guangzhou, Guangdong, China

Site Status RECRUITING

Sun Yat-sen University Cancer Center

Guangzhou, Guangdong, China

Site Status RECRUITING

Shenzhen People's Hospital

Shenzhen, Guangdong, China

Site Status RECRUITING

Countries

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China

Central Contacts

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Yuan-hong Gao, M.D

Role: CONTACT

+86-13560182168

Hui Chang, M.D

Role: CONTACT

+86-13480295989

Facility Contacts

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Tong-chong Zhou, M.D

Role: primary

+86-13808841276

Hai-hua Peng, M.D

Role: backup

+86-15011978349

Bi-Xiu Wen, M.D

Role: primary

+86-18903056780

Cheng-tao Wang, M.D

Role: backup

+86-13711132767

Yuan-hong Gao, M.D

Role: primary

+86-13560182168

Hui Chang, M.D

Role: backup

+86-13480295989

Ya-jie Liu, M.D

Role: primary

+86-13823394075

Shi-hai Wu, M.D

Role: backup

+86-13632935732

References

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Reference Type BACKGROUND

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Other Identifiers

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NACT4-NPC-5010

Identifier Type: -

Identifier Source: org_study_id

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