Introduction to the study
I. Background and purpose of the study
1.Study background
Lung cancer is a common malignant tumor in the world at present, and its incidence and mortality rate rank the first among the causes of death from various malignant tumors. The current poor efficacy of advanced lung cancer is one of the main reasons for the poor overall prognosis of lung cancer. Currently, platinum-based chemotherapy regimens combined with third-generation agents (NCCN clinical practice guidelines recommend the use of vincristine, or gemcitabine, or paclitaxel, etc.) are the standard first-line treatment for advanced lung cancer, with an efficiency rate between 20-30%, a median survival of 7-9 months, a 1-year survival rate of 31 -36% and 2-year survival rate of 10-13%. With tyrosine-kinase inhibitor (TKI)-based targeted agents as first-line treatment options, such as gefitinib (Eressa, Iressa) and erlotinib (Troche, Tarceva), the First-singal and IPASS studies established gefitinib for first-line treatment of NSCLC status, with disease progression-free survival maintained at 9-10 months. Chemotherapy as well as targeted therapy have become important components of a comprehensive treatment regimen for advanced non-small cell lung cancer.
In the context of increasing incidence and mortality of non-small cell lung cancer, it has become an important issue for us to explore new treatment methods to further improve the clinical efficacy, prolong long-term survival and improve the quality of life of advanced lung cancer based on chemotherapy and targeted therapy, which is also the key to improve the overall treatment level of lung cancer.
For a long time, traditional Chinese medicine has played a unique advantage in the treatment of advanced lung cancer, which can prolong survival, improve survival quality and control the growth of lesions. The combination of TCM with chemotherapy can also prolong survival, improve survival, and increase the effectiveness and detoxification, which has been confirmed in many clinical and experimental studies. The Department of Oncology of Longhua Hospital of Shanghai University of Traditional Chinese Medicine has conducted research and exploration on the diagnosis and treatment of lung cancer since the 1960s, and under the leadership of Prof. Liu Jiaxiang, a system of “evidence-based treatment” of TCM guided by the theory of “helping to cure cancer” has been developed. The clinical research and new drug development of Chinese medicine to inhibit lung cancer metastasis and prolong survival have been carried out, and the evidence-based treatment of advanced non-small cell lung cancer by the Chinese medicine Fu Zheng method has good clinical efficacy, showing the characteristics and advantages of Chinese medicine in treating lung cancer and the efficacy of the Chinese medicine Fu Zheng method in inhibiting lung cancer metastasis. The 5-year survival rate after treatment reached the domestic leading and international advanced level. At the same time, we have also developed new drugs Jinfu Kang Oral Liquid and Zhengde Kang Capsules, which have achieved better clinical efficacy, fully reflecting the advantages and characteristics of TCM Fu Zheng method in treating lung cancer with evidence. Based on the above research basis, the Department of Oncology of Longhua Hospital, under the leadership of Professor Liu Jiaxiang, further optimized and integrated the existing effective treatment methods, and formulated a combination of Chinese and Western medicine treatment plan based on the Chinese medicine Fu Zheng method and combined with targeted treatment for clinical application. In order to further improve the quality of survival, prolong the survival period, improve the clinical efficacy of lung adenocarcinoma, better play the important role of Chinese medicine treatment in the multidisciplinary comprehensive treatment of lung cancer, so that the clinical efficacy of lung adenocarcinoma treatment in China is always in the international leading level.
2. Research objectives
A multicenter, large-sample, prospective randomized controlled study was conducted to observe patients with stage IIIa-IV lung adenocarcinoma. The primary efficacy evaluation indexes were: PFS (progression-free survival time); secondary efficacy indexes: ① overall survival OS; ② objective efficiency (tumor control rate); ③ time to progression (TTP); ④ quality of life: EORTC QLQ-L43 scale, TCM evidence score; and also to make an assessment of the toxic side effects and safety of the treatment regimen. It is expected that the Chinese medicine combined with targeted group can prolong the time to progression, overall survival, improve the quality of survival of patients, and the efficacy is better than the targeted treatment alone. The study will provide evidence for optimizing and promoting integrated Chinese and Western medicine treatment regimens.
The study will be conducted in 17 hospitals including Longhua Hospital affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai Pulmonary Hospital affiliated to Tongji University, Chest Hospital affiliated to Shanghai Jiao Tong University, Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Changzheng Hospital affiliated to Second Military Medical University, Shuguang Hospital affiliated to Shanghai University of Traditional Chinese Medicine and Putuo Hospital affiliated to Shanghai University of Traditional Chinese Medicine, and more than 400 subjects are expected to volunteer.
II. Who is not suitable for the study
(1) Have a history of other tumors within 5 years.
(2) Those with first-line targeted therapy and wild-type EGFR gene test; those who have already received targeted therapy or other anti-tumor treatment.
(3) Those with an expected survival of <3 months.
(4) Symptomatic brain metastases.
(5) History of cardiovascular disease: congestive heart failure > in NYHA class II cardiac function. Patients with unstable angina (angina symptoms at rest) or new onset of angina (started in the last 3 months) or myocardial infarction occurring in the last 6 months. Active infection, > grade 2 adverse event (CTC version AE.3.0).
(6) Patients who are pregnant or lactating.
(7) Those with a history of psychiatric disorders that are not easily controlled.
III. What you will need to do if enrolled in the study
1. Before you are enrolled in the study, you will undergo the following tests to determine if you are ready to participate.
Your doctor will ask and record your medical history, perform a physical examination, you will need to have routine blood, stool and urine tests, liver and kidney function, tumor markers and other physical and chemical tests, as well as electrocardiogram, CT and other imaging tests.
2. If you pass the above examinations, the study will be conducted according to the following steps.
Because of the randomized controlled study used in this clinical study, you will be randomly assigned to either the EGFR-TKI targeted therapy group or the TCM combined with EGFR-TKI targeted therapy group based on your condition at the time of enrollment, if you agree to receive targeted therapy.
Trial group: EGFR-TKI targeted therapy drug + oral Chinese medicine
EGFR-TKI-targeted therapy: Erysal or Troche.
Control group: EGFR-TKI-targeted therapy drug + placebo
EGFR-TKI-targeted therapy: ERSA or Troche
Prescribed treatment period: discontinuation of targeted drugs due to disease progression was proposed along with discontinuation of Chinese herbal medicine; if no disease progression occurred in 6 months of taking the drug, the Chinese herbal medicine grant was stopped in the 7th month. Long-term follow-up afterwards: outpatient follow-up by the responsible physician every 1 month.
During the prescribed treatment period, after every 1 course of treatment: you should truthfully reflect the changes in your condition to the doctor, who will give you a physical examination, and also physical and chemical examinations such as blood, urine and stool routine, liver and kidney functions, tumor markers, and imaging examinations according to the situation (you can also provide the doctor with copies of the examination results in other hospitals), and the doctor will explain your physical condition.
During the follow-up period, you will receive an outpatient follow-up visit once a month, and the doctor will arrange the above-mentioned corresponding examination contents for you and inform you of your physical condition. At the same time, the Department of Oncology of Longhua Hospital can provide senior physicians to follow up your treatment with Chinese medicine.
3.Other matters that need your cooperation.
You need to come to the hospital according to the follow-up time agreed between the doctor and you. Your follow-up is very important because your doctor will determine whether the study measures you are receiving are actually working.
You should not use other anti-cancer drugs or remedies for lung cancer during the study period. If you need other treatments, please contact your doctor in advance.
IV. Possible benefits of participating in the study
This treatment plan is based on the combination of oral tonics and EGFR-TKI targeted therapy based on TCM diagnosis and treatment, which are two effective means combined together to form a combined Chinese and Western medicine treatment plan applied to advanced lung cancer, which may improve patients’ quality of survival, prolong progression-free survival time and overall survival time, and may further improve clinical efficacy.
Therefore, if you agree to participate in this study, you and the community will likely benefit from this study. You will receive good medical care during the study. Your quality of life may improve and your time to disease progression and overall survival may or may not be prolonged. However, the information gained through the study may help to further improve treatments for this disease, which may benefit other patients with conditions similar to yours.
V. Possible adverse effects, risks and discomfort, inconvenience of participating in the study
The adverse reactions and risks that may occur during your participation in the study include, but are not limited to, the following. Other unforeseen or even serious adverse reactions may occur with any of the drugs being tested. The physician and the study site will make every effort to prevent and treat any harm that may occur as a result of this study.
The main adverse effects of targeted therapy include loss of appetite, rash, oral mucositis, diarrhea, liver and kidney function impairment, and interstitial lung disease. Herbal therapy is generally well tolerated, and possible adverse reactions include gastrointestinal reactions and fever, which generally do not affect the continuation of treatment. The toxic side effects of targeted therapy vary with the drugs used and the patient’s tolerance, most of them are reversible and can be relieved after discontinuation or symptomatic treatment, while very few can have serious complications or even death. The protocols and drugs used in this study are standardized, efficacious and reliable, expert consensus treatment, and have been more widely used in the clinic.
Your doctor will closely observe the changes in your condition, tell you truthfully about the various phenomena that occur during the study, and actively manage the related adverse reactions for your safety. If you experience any discomfort, new changes in your condition, or any unexpected circumstances during the study, whether or not related to the drug, you should promptly notify your physician, who will make a judgment and medical management of the situation.
If a serious adverse event occurs during the clinical study, the medical expert committee will determine whether it is related to the study protocol, and if it is confirmed to be related, the subject research unit will pay compensation in accordance with relevant Chinese laws.
You will be required to follow up with the hospital on time during the study period and undergo some assessments and examinations, which may cause trouble or inconvenience to you, so please cooperate.
In addition, the study may be ineffective, and the disease may continue to progress due to ineffective treatment or due to comorbidities with other diseases. If, during the study period, the doctor finds that the study measures taken in this study are not effective, the study will be discontinued and other treatment measures that may be effective will be used instead.
VI. Costs involved
You will be responsible for any study-related medical expenses during the study and follow-up period. You will be responsible for the cost of treatment and tests required for other co-morbidities.
In the event of a serious adverse event caused by the study protocol (to be confirmed by the investigator and the project unit in charge), the study unit will pay for your medical expenses.
VII. Is personal information confidential?
All information collected during the study will be kept confidential and will be kept by the hospital and the investigator. Your medical records (study medical records, examination reports, etc.) will be kept intact at the hospital, and the doctor will record the results of the examination in your outpatient medical record. The study physician, the investigator caring for you, the inspector appointed by the sponsor, and the State Food and Drug Administration will be allowed access to your medical records. You will be identified by your initials and patient study number only, and your personal identity will not be disclosed in any public reports or publications regarding the results of this study. We will make every effort to protect the privacy of your personal medical information to the extent permitted by law.
It is possible that your medical records and pathology specimens may be reused in future studies other than this study. You may now also declare your refusal to have your medical records and pathology specimens used in studies other than this study.
Voluntary choice to participate in the study and to withdraw from the study
Your participation in the study is entirely voluntary. You may refuse to participate in the study or withdraw from the study at any time during the study, and this will not affect the relationship between you and your physician, nor will it affect your medical care or any other loss of benefits.