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

Sun Yat-sen University

Status and phase: Enrolling; Phase 3

Conditions: Nasopharyngeal Carcinoma

Treatments: Radiation: Concurrent chemoradiation (CCRT); Drug: Docetaxel (DOC); Drug: Cisplatin (DDP)

Study type: Interventional

Funder types: Other

Identifiers

NCT02512315

NACT4-NPC-5010

Details and patient eligibility

About

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.

Full 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.

Enrollment: 192 estimated patients

Sex: All

Ages: Under 70 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

192 participants in 2 patient groups

CCRT group (Group A)

Active Comparator group

Description:

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

Treatment:

Radiation: Concurrent chemoradiation (CCRT)

NACT-CCRT group (Group B)

Experimental group

Description:

Patients who are allocated into in this group will be treated with 4 cycles of neoadjuvant chemotherapy (NACT, docetaxel plus cisplatin) followed by CCRT.

Treatment:

Drug: Cisplatin (DDP)

Drug: Docetaxel (DOC)

Radiation: Concurrent chemoradiation (CCRT)