Clinical trial NCT02512315: A Trial On 4 Cycles Of Neoadjuvant Chemotherapy Plus Concurrent Chemoradiation In N2-3 Nasopharyngeal Carcinoma
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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Nasopharyngeal Carcinoma
Keywords: Nasopharyngeal carcinoma
Neoadjuvant chemotherapy
Concurrent chemoradiation
Distant metastasis
Survival
Lead sponsor: Sun Yat-sen University
Sponsor class: OTHER
First posted: 2015-07-30
Enrollment: 192
Sex: ALL
Maximum age (years): 70
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: 5-year overall survival (5y-OS)
timeFrame: 5 years after the date of pathologic diagnosis
measure: 5-year distant-metastasis-free survival (5y-MFS)
timeFrame: 5 years after the date of pathologic diagnosis
Secondary outcomes:
measure: 5-year local-relapse-free survival (5y-RFS)
timeFrame: 5 years after the date of pathologic diagnosis
measure: 5-year disease-free survival (5y-DFS)
timeFrame: 5 years after the date of pathologic diagnosis
measure: Incidence of grade 3/4 adverse event
timeFrame: Once a week during therapy, up to 7 weeks (Group A) or 19 weeks (Group B)
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Cancer Center of Guangzhou Medical University
state: Guangdong
city: Guangzhou
country: China
facility: First Affiliated Hospital of Sun Yat-sen University
state: Guangdong
city: Guangzhou
country: China
facility: Sun Yat-sen University Cancer Center
state: Guangdong
city: Shenzhen
country: China
facility: Shenzhen People's Hospital
state: Guangdong
Study officials:
affiliation: Sun Yat-sen University
name: Yuan-hong Gao, M.D
role: PRINCIPAL_INVESTIGATOR
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