Clinical trial NCT03529279: CNG Staging Compared With 8th UICC of NPC for Treatment Decision-marking and Selection of Chemotherapy and Radiotherapy
Official title: CNG Staging Compared With UICC Eighth Staging of Nasopharyngeal Carcinoma for Treatment Decision-marking and Selection of Chemotherapy and Radiotherapy： a Multicenter, Open Label, Randomized Controlled, Non-inferiority Clinical Trial
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE3
Conditions: Nasopharyngeal Carcinoma
Lead sponsor: Sun Yat-sen University
Sponsor class: OTHER
First posted: 2018-05-18
Enrollment: 1324
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Due to the increase of tumor control rate and survival rate in era of IMRT, the role of the seventh edition of UICC/AJCC staging system in predicting prognosis is becoming weaker and inaccurate.

Therefore, we put forward a new staging for the clinical staging of NPC in the era of IMRT without changing the current T, N, M staging definition of the 7th of the UICC/AJCC staging system. We call this new stage "Cooperative Nasopharyngeal Carcinoma Group" stage, namely CNG stage. In CNG stage, the clinical stages were reduced to three stages, namely, CNG I stage includes T1-3N0-1M0 and T1-2N2M0, CNG II stage includes T3N2M0, T4N0-2M0 and TanyN3M0, CNG III stage includes TanyNanyM1. For CNG I stage, the IMRT alone is sufficient. If EBV-DNA copies is more than 0 copy/ml, concurrent chemoradiotherapy will be given. For CNG II stage, patients can benefit from combined radiotherapy and chemotherapy. For CNG III stage, patients are recommended for systemic chemotherapy plus local radiotherapy (primary focus, neck drainage area and distant metastasis).

This year, UICC/AJCC has proposed an eighth edition of NPC staging system. The eighth version is mainly changed in the definition and refinement of the anatomic location compared with the seventh edition. This is different from our new CNG staging concept.

Therefore, CNG staging and its treatment strategy was used as the experimental group, and the eighth edition of UICC/AJCC staging with NCCN guiding treatment was used as the control group. The open and randomized controlled clinical study was conducted. The purpose of this study was to evaluate in the era of IMRT, CNG staging can be better than UICC/AJCC eighth clinical staging for treatment decision-marking and selection of chemotherapy and radiotherapy, and differentiating differences in prognosis in each clinical stage. The survival results based on CNG staging and its treatment are not inferior to the survival results of the NCCN guide therapy based on the eighth edition UICC/AJCC staging, to avoid chemotherapy for some of the patients, and to improve the outcome of metastatic patients.

Detailed description: The seventh edition of the UICC/AJCC staging system, which is widely used in recent years, is based on survival data in the traditional era of radiotherapy. However, the survival of nasopharyngeal cancer patients has been greatly improved in the era of modern radiation therapy, which IMRT (Intension Modulated Radiotherapy) is widely used. Even with radiotherapy alone, the 5 year disease specific survival rate of nasopharyngeal carcinoma with stage I-II is more than 95%, the 3 year overall survival rate of non metastatic III-IV patients is about 75%, and the 5 year overall survival rate is about 80%. The 5 year survival rate of metastatic nasopharyngeal carcinoma can reach more than 20% with systemic treatment. Due to the increase of tumor control rate and survival rate in era of IMRT, the role of the seventh edition of UICC/AJCC staging system in predicting prognosis is becoming weaker and inaccurate.

Therefore, in the previous study, we put forward a new staging for the clinical staging of nasopharyngeal carcinoma in the era of IMRT without changing the current T, N, M staging definition of the seventh edition of the UICC/AJCC staging system. We call this new stage "Cooperative Nasopharyngeal Carcinoma Group" stage, namely CNG stage. In CNG stage, the clinical stages were reduced to three stages, namely, CNG I stage includes T1-3N0-1M0 and T1-2N2M0, CNG II stage includes T3N2M0, T4N0-2M0 and TanyN3M0, CNG III stage includes TanyNanyM1, and the 5 year DSS (Disease specific survival) is 93.3%, 72.7%, and 24%, respectively, with a significant difference.

This year, UICC/AJCC has proposed an eighth edition of nasopharyngeal carcinoma staging system based on the revision of the seventh edition. The main updates are: (1) add the definition of the T0 phase, that is, the EBV positive cervical lymph node metastases with uncertain primary foci, and (2) the invasion of the adjacent muscles (including the pterygus, the extradypterygus, and the anterior vertebroid muscle) into T2; (3) replace the "masticatory muscle space" and "subtemporal fossa" in the previous T4 definition with a specific description of soft tissue invasion; (4) change the supraclavicular fossa to the lower neck (defined as the lymph node metastases below the subchondral edge); (5) N3a and N3b are combined called N3, and it is defined as a single / double neck lymph node with long diameter \> 6cm, and/or below the subchondral subchondral edge; (6) the IVA stage (T4 N0-2 M0) and the IVB stage (anyT N3 M0) are combined called IVA stage; (7) the IVC stage (anyT anyN) is changed to IVB stage. The eighth version is mainly changed in the definition and refinement of the anatomic location compared with the seventh edition. Except for the migration of the adjacent muscle invasion, and the other changes are not significant. The upper bound of N3 is moved from the supraclavicular fossa to the subchondral edge in N staging. This is different from our new CNG staging concept.

CNG staging of nasopharyngeal carcinoma is related to the unique biological behavior of nasopharyngeal carcinoma, which is consistent with the three clinical patterns of nasopharyngeal carcinoma, namely, non metastasis, tendency to metastasis and metastasis. The pattern of tendency to metastasis was related to the late T and N staging. Based on the biological behavior and clinical survival data of NPC, we further proposed the treatment strategy of nasopharyngeal carcinoma under the guidance of CNG staging, that is, the CNG I stage is consistent with the non metastasis model, and the IMRT alone is sufficient. The CNG II stage is consistent with the tendency to metastasis mode, which can benefit from combined radiotherapy and chemotherapy. The CNG III stage is metastatic mode, which is recommended for systemic chemotherapy plus local radiotherapy (primary focus, neck drainage area and distant metastasis). In clinical practice, we suggest that for patients with CNG I stage, if EBV-DNA copies is more than 0 copy/ml, concurrent chemoradiotherapy will be given.

Therefore, CNG staging and its treatment strategy was used as the experimental group, and the eighth edition of UICC/AJCC staging with NCCN guiding treatment was used as the control group. The open and randomized controlled clinical study was conducted. The purpose of this study was to evaluate in the era of IMRT, CNG staging can be better than UICC/AJCC eighth clinical staging for treatment decision-marking and selection of chemotherapy and radiotherapy, and differentiating differences in prognosis in each clinical stage. The survival results based on CNG staging and its treatment are not inferior to the survival results of the NCCN guide therapy based on the eighth edition UICC/AJCC staging, to avoid chemotherapy for some of the patients, and to improve the outcome of metastatic patients.

Eligibility criteria: Inclusion Criteria:

* Pathologically confirmed and previously untreated nasopharyngeal carcinoma
* Non T1N0M0 patient according to UICC/AJCC seventh edition staging system
* Age ≥ 18 years and \< 65 years
* Karnofsky performance status (KPS) score ≥ 70
* Adequate normal organ function
* No history of other malignant tumors
* No serious mental disorder (schizophrenia, delusion of victimization, manic depression, and drug induced anxiety)
* No AIDS, active pulmonary tuberculosis and other serious immunodeficiency diseases
* No communication barrier, can answer the question
* Sign informed consent under voluntary circumstances, complete treatment and follow up as required

Exclusion Criteria:

* Poor compliance
* Investigators consider as inappropriate for enrolling into this study

Primary outcomes:
measure: Overall Survival (OS)
timeFrame: From the date of randomization until the date of death, assessed up to 60 months
Secondary outcomes:
measure: Quality of life
timeFrame: From the date of radiotherapy begin, every week during radiotherapy, assessed up to 60 months
measure: Recurrence free survival (RFS)
timeFrame: From the date of randomization until the date of first recurrence, assessed up to 60 months
measure: Distant metastasis free survival (DMFS)
timeFrame: From the date of randomization until the date of first distant metastasis, assessed up to 60 months
measure: Disease specific survival (DSS)
timeFrame: From the date of randomization until the date of death from tumor, assessed up to 60 months
measure: Complete remission (CR)
timeFrame: From the date of randomization, 3 months after radiotherapy
measure: Incidence of side effects associated with tumor therapy
timeFrame: From the date of randomization up to 60 months
Other outcomes:
Locations:
Study officials:
affiliation: Sun Yat-sen University
name: Yun-fei Xia, M.D
role: PRINCIPAL_INVESTIGATOR
References: