Efficacy Study of Comprehensive Rehabilitation Program Plus Chemotherapy in Postoperative NSCLC Patients

Study Overview
=================
Brief Summary
-----------------
The investigators performed a multi-centered, randomized, placebo-controlled, prospective clinical trial on the effect of comprehensive rehabilitation program plus chemotherapy to improve quality of life(QOL) and long-term survival of postoperative non small cell lung cancer（NSCLC）patients with high risk stages IB to IIIA. The investigators plan to enroll 354 cases in 3 years (118 cases for chemotherapy plus rehabilitation training and traditional Chinese medicine (TCM), 118 cases for chemotherapy plus rehabilitation education and TCM,118 cases for chemotherapy plus rehabilitation education and placebo), expecting that comprehensive rehabilitation program plus chemotherapy has a better efficacy on improving QOL and long-term survival.

Detailed Description
-----------------
NSCLC is one of the malignancies with high incidence and mortality. In recent years, surgery become the preferred treatment for early stage of NSCLC. Patients with high risk stages IB to IIIA may undergo radical surgery and complete 4-6 cycles of adjuvant chemotherapy. 5 year survival rate increased from 43.5% to 48.8%, but some patients will end chemotherapy because of the side effects of chemotherapy. Comprehensive rehabilitation program may alleviate the side effects as an effective treatment which including rehabilitation training and TCM. The investigators performed a multi-centered, randomized, placebo-controlled, prospective clinical trial on the effect of comprehensive rehabilitation program plus chemotherapy to improve quality of life(QOL) and long-term survival of postoperative patients who need complete postoperative chemotherapy with high risk stages IB to IIIA. Patients are randomized into A observational group (chemotherapy plus rehabilitation training and TCM), B observational group(chemotherapy plus rehabilitation education and TCM) and control group (chemotherapy plus rehabilitation education and placebo). The treatment should be last three months and the patients will be followed up regularly. The primary efficacy assessments are: (1) QOL (QLQ-LC43 scale); (2) Pulmonary function test(PFTs): 1) Forced vital capacity (FVC); 2) Forced expiratory volume in one second (FEV1); 3) Forced expiratory flow rate from 25% to 50% (FEF25-50); 4) Residual volume (RV); 5) Total lung capacity (TLC). Secondary efficacy assessments are: (1) 2 years disease-free survival; (2) TCM symptoms changes; (3) Tumer markers (CEA, CA-125 and CYFRA21-1); (4) Exercise tolerance; (5) Toxicity, side effects and security of the treatments will be assessed at the same time. The investigators plan to enroll 354 cases in 3 years (118 cases for chemotherapy plus rehabilitation training and traditional Chinese medicine (TCM), 118 cases for chemotherapy plus rehabilitation education and TCM,118 cases for chemotherapy plus rehabilitation education and placebo), expecting that comprehensive rehabilitation program plus chemotherapy has a better efficacy on improving QOL and long-term survival.

Official Title
-----------------
Clinical Study on the Effect of Comprehensive Rehabilitation Program Plus Chemotherapy Versus Chemotherapy on Quality of Life in Postoperative Non Small Cell Lung Cancer Patients With Stage IB-IIIA

Conditions
-----------------
Non-small Cell Lung Cancer

Intervention / Treatment
-----------------
* Behavioral: Rehabilitation Training
* Drug: TCM
* Other: Rehabilitation Education
* Drug: placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients with completely resected stage IB-IIIA non-small-cell lung cancer who will receive chemotherapy for the first time within 6 weeks after the operation. Between the ages of 18 to 75 years old; The score of ECOG ≥2 points Without major organ dysfunction: hemoglobin ≥10 g/dL, absolute neutrophil count (ANC) ≥1.5*10^9/L, platelets ≥100 *10^9/L; normal hepatic and renal function Exclusion Criteria: Indefinite pathological diagnosis; Expected survival time < 6 months Combined with heart, liver, kidney and hematopoietic system and other serious diseases The patient was treated with antibiotics or infected one week before the test; Pregnant or child breast feeding women; Mental or cognitive disorders;

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 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
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Chemotherapy+Training+TCM<br>Adjuvant Chemotherapy is performed within 6 weeks after operation. Rehabilitation training is mainly composed of gymnastic qigong, which will be started in one month after operation. Prescriptions formulated into granules origin from Professor Xu Ling in Yueyang hospital. Package of granules is made into four types with functions such as benefiting Qi recipe, benefiting Yin recipe, harmonizing stomach recipe, detoxication and resolving masses recipe. Patients will take harmonizing stomach recipe granules for the first week after chemotherapy and syndrome differentiation granules in TCM for second weeks from the end of chemotherapy. The patient will take TCM granules for 3 months. | Behavioral: Rehabilitation Training<br>* Patients will be trained in one month after operation. Rehabilitation training will be carried out between every two cycles of chemotherapy. Rehabilitation training is mainly composed of gymnastics qigong, which has long been regarded as a form of rehabilitation in Traditonal Chinese Medicine. According to the poor pulmonary function of patients with lung cancer after operation, Liu Zi Jue lung exercise is chosen to strengthen the pulmonary function of the human body in Chinese traditional health culture. Liu Zi Jue lung exercise intervention will be lead by an expert instructor, five times a week, 15 min/time.<br>* Other names: Liu Zi Jue lung exercises;Drug: TCM<br>* four types with functions such as benefiting Qi recipe, benefiting Yin recipe, harmonizing stomach recipe and detoxication and resolving masses recipe. Each package contained 20g of water-soluble herbal granules that were manufactured at a Good Manufacture Practice standard facility (Tian Jiang Ltd, Jiangyin, China). Each package was labeled with a serial number. The prescription form comprised the stock list with both the name and serial number.<br>* Other names: Prescriptions from Professor Xu Ling;|
| Experimental: Chemotherapy+Education+TCM<br>Adjuvant Chemotherapy is performed within 6 weeks after operation. Patients who received rehabilitation education will not accept rehabilitation training. Prescriptions formulated into granules origin from Professor Xu Ling in Yueyang hospital. Package of granules is made into four types with functions such as benefiting Qi recipe, benefiting Yin recipe, harmonizing stomach recipe, detoxication and resolving masses recipe. Patients will take harmonizing stomach recipe granules for the first week after chemotherapy and syndrome differentiation granules in TCM for second weeks from the end of chemotherapy. The patient will take TCM granules for 3 months. | Drug: TCM<br>* four types with functions such as benefiting Qi recipe, benefiting Yin recipe, harmonizing stomach recipe and detoxication and resolving masses recipe. Each package contained 20g of water-soluble herbal granules that were manufactured at a Good Manufacture Practice standard facility (Tian Jiang Ltd, Jiangyin, China). Each package was labeled with a serial number. The prescription form comprised the stock list with both the name and serial number.<br>* Other names: Prescriptions from Professor Xu Ling;Other: Rehabilitation Education<br>* General health education<br>* Other names: health education;|
| Placebo Comparator: Chemotherapy+Education+Placebo<br>Adjuvant Chemotherapy is performed within 6 weeks after operation. Patients who received rehabilitation education will not accept rehabilitation training. Patients who received rehabilitation education will not accept rehabilitation training. We compromise the raw materials for the placebo including food color and artificial flavors. The placebo and therapeutic packages were stored in different cabinets, and only the dispensing technician knew the contents of the packages. The patient will take placebo granules for 3 months. | Other: Rehabilitation Education<br>* General health education<br>* Other names: health education;Drug: placebo<br>* four types with functions such as benefiting Qi recipe, benefiting Yin recipe, harmonizing stomach recipe and detoxication and resolving masses recipe，with the same color, smell，taste, weight and package<br>* Other names: control;|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in Quality of life (QOL) | QOL is assessed using European Organization for Research and Treatment of Cancer Quality of Life QuestionnaireLung Cancer 43 (EORTC QLQ-LC43). | Time Frame: baseline, at 4 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Residual capacity (RV) | RV is measured in a test known as Lung valume(LV)spirometry,a type of pulmonary function test.RV is the volume of air remaining in the lungs after a maximal expiratory effort. | after intervention at 2 weeks | 
| Total lung capacity（TLC） | TLC is measured in a test known as Lung valume(LV)spirometry,a type of pulmonary function test.TLC equals the vital capacity plus the residual capacity. | after intervention at 2 weeks | 
| Forced vital capacity (FVC) | FVC is the volume of air exhaled with maximum effort and speed after a full inspiration. FVC is measured in a test known as spirometry, a type of pulmonary function test. | after intervention at 2 weeks | 
| Forced expiratory volume in one second(FEV1) | FEV1 is an individual test measure used to assess limitations in airflow, a type of pulmonary function test,which measures the amount of air exhaled in onesecond. | after intervention at 2 weeks | 
| Maximum mid expiratory flow(MMEF) | MMEF is forced expiratory flow between 25% and 75% of forced vital capacity,a type of pulmonary function test. | after intervention at 2 weeks | 
| Disease-free survival (DFS) | Time from randomization to first recurrence or metastasis | From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 months | 
| TCM symptoms changes | TCM symptoms changes are according to the lung cancer symptom classification quantization table in Guiding Principles for Clinical Research of Traditional Chinese Medicine in the Treatment of Lung Cancer (2002 Edition) | after intervention at 4 months | 
| Tumor markers | Tumor markers include CEA, CA-125 and CYFRA21-1 | after intervention at 4 months | 
| Safety assessment evaluated according to Common Toxicity Criteria | Safety assessment is evaluated according to Common Toxicity Criteria (CTC 3.0) | after intervention at 4 months |