To Investigate the Molecular Mechanism of Traditional Chinese Medicine Constitution Using Next-generation Sequencing in Nasopharyngeal Carcinoma

Study Overview
=================
Brief Summary
-----------------
To investigate the molecular mechanism of traditional Chinese medicine constitution, the investigators proposed a randomized, double-blind, placebo-controlled, phase II trial to recruit 120 patients with nasopharyngeal cancer. Next generation sequencing, immune repertoire, gut microbiota, traditional Chinese medicine constitution and tongue diagnosis would be examined before/after 16 weeks of treatment of Danggui Buxue Tang from the beginning of concurrent chemoradiotherapy in this project. The correlation between different examinations would be analyzed to investigate the molecular mechanism of traditional Chinese medicine constitution. Disease survival, recurrence, and quality of life would be also followed up for two years to evaluate the benefit of Danggui BuxueTang.

Detailed Description
-----------------
The basis for academic excellence is the interdisciplinary cooperation. The individualized medicine is the future trends, and the theory of body constitution is the most potential study for the individualized medicine and to research the process and prognosis of disease. Technique of next-generation sequencing (NGS) is also involved to comprehend to the mechanism of the prescriptions under the theory of body constitution. The nasopharyngeal cancer is a Chinese-specific disease, and radiation therapy has remarkable effect. There are many studies proving that Traditional Chinese medication can relieve the side effect of radiation therapy. The study will combine next-generation sequencing and TCM diagnostic tool, and analyze the transformation of body constitution and the performance of genes related to radiation therapy. The results may reveal the molecular mechanism of TCM constitutions and the benefit of Danggui BuxueTang, and may be used for early screen and prevention to other cancers or diseases. Furthermore, it can help to develop the potential drugs. The study plans to collect 120 cases within two years. The participants would be divided randomly to the experimental group and control group. The blood sample would be taken for next generation sequencing analysis before the radiation therapy, and after the radiation therapy combined with traditional Chinese medication. The result of samples would be compared with each other to identify Qi deficiency gene and TCM effective gene.

Official Title
-----------------
To Investigate the Molecular Mechanism of Traditional Chinese Medicine Constitution Using Next-generation Sequencing in Nasopharyngeal Carcinoma

Conditions
-----------------
Nasopharyngeal Carcinoma

Intervention / Treatment
-----------------
* Drug: Danggui Buxue Tang
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients with pathological diagnosis of nasopharyngeal carcinoma stage II   IVa (AJCC eighth edition) preparing to receive concurrent chemoradiotherapy Exclusion Criteria: Pregnant or lactating women ECOG PS (ECOG performance status) scores of over 2 points for each day's performance assessment Take anticoagulants or antiplatelet agents such as aspirin, warfarin, etc. Cannot accept routine treatment, or can not cooperate with the research program

Ages Eligible for Study
-----------------
Minimum Age: 20 Years
Maximum Age: 70 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: 120 subjects are divided into experimental group and control group (placebo).
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Danggui Buxue Tang group<br>Use Danggui Buxue Tang 5g/time, 3 times a day, for 12 weeks. | Drug: Danggui Buxue Tang<br>* Danggui Buxue Tang is an extracted powder of traditional Chinese medicine formula.<br>|
| Placebo Comparator: Placebo group<br>Use Placebo 5g/time, 3 times a day, for 12 weeks. | Drug: Placebo<br>* Placebo is a very low dose Danggui Buxue Tang powder.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The correlation between next-generation sequencing analysis and traditional Chinese medicine constitution | Identification of biomarkers by next-generation sequencing analysis in nasopharyngeal cancer patients. | The biomarker as assessed by Next-generation sequencing analysis, Change from baseline in the gene expression at 16 weeks of treatment of Danggui Buxue Tang from the beginning of concurrent chemoradiotherapy and 2-year follow-up. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The quality of life as assessed by the score of questionnaire of European Organisation for Research and Treatment of Cancer C30 | The quality of life for cancer patients as assessed by the score of cancer-specific questionnaire, European Organisation for Research and Treatment of Cancer (EORTC C30), which is cancer-specific core questionnaire for use in various cancers with 30 in Functional scales (physical, role, cognitive, emotional, social), symptom scales (fatigue, pain, and nausea and vomiting), global health status and quality of life scale, also several single-item symptom measures etc), with range from 1 (Not at all) to 4 (Very much), and from 1 (Very poor) to 7 (Excellent), scoring from 0 to 100. For functional and global quality of life scales, higher scores mean a better level of functioning. For symptom-oriented scales, a higher score means more severe symptoms. | Change from baseline in score of questionnaire at 16 weeks of treatment of Danggui Buxue Tang from the beginning of concurrent chemoradiotherapy and 2-year follow-up. | 
| The quality of life as assessed by the score of questionnaire of European Organisation for Research and Treatment of Cancer H&N35 | The quality of life as assessed by the score of a head & neck cancer-specific questionnaire, European Organisation for Research and Treatment of Cancer Head and Neck Module (EORTC H&N35), with 35 items to evaluate symptoms encountered by patients with head and neck cancer in 18 domains, including in 7 multiple-item scales (Pain, Swallowing, Senses, Speech, Social eating, Social contact, and Sexuality) and 11 single items (eg, Opening mouth, Sticky saliva, Dry mouth, etc), with range from 1 (Not at all) to 4 (Very much), and from 1 (Very poor) to 7 (Excellent). EORTC H&N35)have standardized scores ranging from 0 to 100, with higher scores indicating a greater degree of symptoms. | Change from baseline in score of questionnaire at 16 weeks of treatment of Danggui Buxue Tang from the beginning of concurrent chemoradiotherapy and 2-year follow-up. | 
| Survival rate | Survival after treatment | throughout the study, an average of 2 year | 
| Disease recurrence | Disease recurrence after treatment | throughout the study, an average of 2 year | 
| Next-generation sequencing | The comparison of next-generation sequencing of human gene analysis after treatment | pre-treatment and after 16 weeks of treatment | 
| Immune repertoire | The comparison of IgG, IgA and T cell receptor immune repertoire after treatment | pre-treatment and after 16 weeks of treatment | 
| Microbiota | The comparison of gut microbiota after treatment | pre-treatment and after 16 weeks of treatment | 
| Tongue diagnosis | The comparison of Tongue diagnosis after treatment | pre-treatment and after 16 weeks of treatment | 
| Constitution in Chinese Medicine Questionnaire (CCMQ) | The Chinese medicine constitution as assessed by the score of Constitution in Chinese Medicine Questionnaire, consists of 60 items in 9 types of Chinese medicine constitution, gentleness, Qi-deficiency, Yang-deficiency, Yin-deficiency, phlegm-dampness, dampness-heat, blood-stasis, Qi-stagnation, and special diathesis, with scaling range from 1(None) to 5(Always). The score would be transform to adjusted scores as｛[ (Total - the number of items)/( the number of items×4)]×100｝with range from 0-100. A higher score indicates that the subject may be more likely to have the specific constitution. | Change from baseline in score of questionnaire at 16 weeks of treatment of Danggui Buxue Tang from the beginning of concurrent chemoradiotherapy and 2-year follow-up. | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Nasopharyngeal carcinoma, Concurrent chemo-radiotherapy