The Evaluation of Curative Effect on Treatment of Tumor Above Thalidomide Combined With Megestrol

Study Overview
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Brief Summary
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To observe the effect of thalidomide combined with megestrol acetate on lymphocyte, inflammatory factor regulation and nutritional status in patients with advanced malignant tumors.

Detailed Description
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This study was to select 200 patients with advanced tumors with an estimated survival of ≥ 2 months. 50 patients were randomly assigned to each group. The patients were divided into chemotherapy group, chemotherapy combined with thalidomide and megestrol acetate group, The best supportive treatment group, the best supportive treatment combined with thalidomide and megestrol acetate group. The chemotherapy group and the best supportive treatment group were the control group. The combined group was administered continuously for 8 weeks according to thalidomide 100 mg qn po and megestrol acetate 0.16 qd po. Calculating the sum of the longest diameters of the target lesions from each patient before and 8 week after treatment. Patients in each group before treatment, 4th week, and 7th week were observed T cell subsets, B cell subsets, NK cell subsets and the expression of inflammatory cytokines. Through nutritional assessment Table (PG-SGA), Multidimensional Deficit Power Meter (MFSI-SF), Quality of Life Assessment Scale (EORTC QLQ-C30), Prognostic Assessment Form (GPS), Physical Status Assessment Form (ECOG) and lean body mass, upper arm muscle circumference and upper arm muscle area analysis of the effect of thalidomide combined with megestrol acetate on the nutritional status of patients with advanced cancer which reveal that thalidomide combined with megestrol acetate may improve the immune regulation and nutritional status of patients with advanced malignant tumors mechanism.

Official Title
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Prospective Clinical Study of the Effect of Thalidomide Combined With Megestrol Acetate on Lymphocyte, Inflammatory Factor Regulation and Nutritional Status in Patients With Advanced Malignant Tumors

Conditions
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Cancer, Therapy-Related

Intervention / Treatment
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* Drug: Chemotherapy drugs
* Drug: thalidomide and megestrol acetate
* Other: optimal support treatment
* Drug: thalidomide and megestrol acetate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with advanced malignant tumor confirmed by histopathology or cytology (hepatocarcinoma can be clinical diagnosis) Must be able to swallow pills The age of the tester ≥ 18 years old Gender is not limited Kamofsky score > 20 points Estimated survival period ≥ 2 months Childbearing age Women need negative pregnancy test Patients voluntarily sign informed consent and receive follow-up The tester can cooperate to observe adverse events and efficacy All of the above conditions can be included Exclusion Criteria: Active upper digestive tract ulcers, obvious vomiting, chronic diarrhea, intestinal obstruction, malabsorption, etc; other patients have been known to affect drug absorption, distribution, metabolism or clearance 2 or more important organ dysfunction Thrombosis Embolism history, except for thrombosis caused by PICC Patients suspected of having a history of allergy to thalidomide tablets Any significant clinical and laboratory abnormalities that researchers believe affect safety evaluators, such as: uncontrollable activity Microbial infection, grade II or above peripheral neuropathy (NCI CTC AE v4.0), congestive heart failure, myocardial infarction within 6 months, chronic kidney disease, thyroid dysfunction etc, and acceptance may bring significant metabolic or weight changes Patients with clinical disposition Patients with mental disorders, affecting the efficacy of the assessor During the trial period and within 3 months after the end of the trial, the subject and his partner are not willing to contraception Any of the above can not be enrolled.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: 200 patients with advanced tumors with a predicted survival period of ≥2 months were selected, including 100 patients with chemotherapy indications (50 patients were divided into chemotherapy group and 50 patients were divided into chemotherapy combined with TH and MG group according to the random principle) and 100 patients without chemotherapy indications (50 patients were randomly divided into the best supportive treatment group and 50 patients were randomly divided into the best supportive treatment group with TH and MG according to the random principle). The chemotherapy alone group and the best supportive treatment group were the control group. The thalidomide and megestrol acetate administration groups were administered with thalidomide 100 mg qn po and megestrol acetate 0.16 qd po for 8 weeks.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: chemotherapy group<br>the patients were recepted chemotherapy alone | Drug: Chemotherapy drugs<br>* According to the NCCN Guidelines<br>|
| Experimental: chemotherapy combined with TH and MG group<br>the patients were recepted chemotherapy combined with thalidomide and megestrol | Drug: thalidomide and megestrol acetate<br>* The thalidomide and megestrol acetate administration groups were administered with thalidomide 100 mg qn po and megestrol acetate 0.16 qd po for 8 weeks<br>* Other names: Chemotherapy drugs;|
| Experimental: the best supportive treatment group<br>the patients were recepted the best supportive without chemotherapy | Other: optimal support treatment<br>* Patients who cannot tolerate chemotherapy and other cancer treatments receive optimal support for 8 weeks<br>|
| Experimental: the best supportive treatment combined with TH and MG group<br>the patients were recepted the best supportive combined with thalidomide and megestrol without chemotherapy | Drug: thalidomide and megestrol acetate<br>* The thalidomide and megestrol acetate administration groups were administered with thalidomide 100 mg qn po and megestrol acetate 0.16 qd po for 8 weeks<br>* Other names: optimal support treatment;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Imaging efficacy evaluation | Clinical response Based on the Response Evaluation Criteria Solid Tumors (RECIST), the therapeutic effect was divided into complete response (CR), partial response (PR), stable disease (SD), progressive disease (PD). Investigators calculate the sum of the longest diameter of the target lesions from each patient by CT or MRI. | before and 8 week after treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Observing the expression of lymphocyte subsets | Patients were detected Lymphocyte subgroups of 2 ml peripheral blood by Flow cytometer (BD FACSCalibur), which inclunde the T cell subsets, NK cell subset, B cell subset(percentage) | before , the fourth and the seventh weeks of treatment | 
| Observing the expression of inflammatory factors | 2 ml of peripheral blood was taken from each patient. Flow cytometry was used to detect changes of inflammatory factor expression which include the IL-2, IL- 4, IL-5, IL-6, IL-9, IL-10, IL-13, IL-17A, IL-17F, IL-21, IL-22, IFN-γ and TNF-α(ug/ml) | before , the fourth and the seventh weeks of treatment | 
| Nutritional assessment | Scored Patient-Generated Subjiective Global Assessment（PG-SGA）form was used in the present study. The total score of PG-SGA is summed by the following four subscale scores（A+B+C+D）. The first measurement score（A）is self-assessed by the subject and consists of the following four parts: Weight Table（0-4），Eating Situation Table（0-6），Symptom Table （0-22），Activity and Body Function Table（0-3）. The remaining three measurements are completed by trained registered clinical physicians， dieticians，and nurses: Scale of relationship between disease and nutritional needs（B）（0-6），Metabolic demand scale（C）（0-9），Physical examination scale（D）（0-24）. The scoring was controlled by one researcher (H.R). The lower scores represent a better outcome and the higher scores represent a worse outcome. | before , the fourth and the seventh weeks of treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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thalidomide, megestrol acetate, tumor, lymphocyte, inflammatory cytokines, nutritional