Zoledronic Acid Combined Radiotherapy for Bone Metastasis of Non-small Cell Lung Cancer

Study Overview
=================
Brief Summary
-----------------
This study will give comparison of the bone pain remission and the adverse reaction of Zoledronic acid combine with High dose fractionation radiotherapy(30Gy/10f) and Zoledronic acid combine with low dose fractionation radiotherapy(15Gy/5f) . The purpose of this trial is to prove whether Zoledronic acid combine radiotherapy can reduce radiotherapy dose in treatment of non-small cell lung cancer bone metastasis'pain relief or not.

Detailed Description
-----------------
Further study details as provided by oncology center of Daping hospital

Official Title
-----------------
Zoledronic Acid Combined Radiotherapy for Bone Metastasis of Non-small Cell Lung Cancer: A Non-inferiority, Randomized, Open, Parallel and Controlled Prospective Clinical Study

Conditions
-----------------
Non-small Cell Lung Cancer, Bone Metastasis

Intervention / Treatment
-----------------
* Drug: Zoledronic acid
* Radiation: Radiotherapy


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Pathology or cytology was diagnosed with non-small cell lung cancer, and bone metastases was confirmed by CT or MRI , and the patients have to need intervention treatment. VAS score>2 points. No paraplegia, No pathological fractures of bone related events which require surgical intervention, No major organ dysfunction,laboratory indexes meet the following requirements: Haemamoeba >4.0 x 10^9/L, Neutrophile granulocyte > 2 x 10^9/L, the platelet count>100 x 10^9/L, hemoglobin>100 g/L; Liver result: the serum bilirubin is lower than normal ceiling; ALT and AST is lower than the maximum normal 1.5 times; Cr<265 umol/l or 3.0 mg/dl, creatinine clearance>60 ml/min. Exclusion Criteria: The patients who have allergy of Bisphosphonates and zoledronate. The patients who receive Molecular targeted therapy and chemotherapy within one month，The patients who receive Calcitonin and Aminoglycoside therapy in one week. The patients who receive Pamidronic Acid in 28 days，The patients original sites receive radiotherapy before. The patients who have history of thyroid surgery，receive tooth extraction in 2 weeks，and have been suffered from Bone Fracture and paraplegia. The patients who have Serious internal medicine diseases and acute infection. The patients With a history of psychiatric Pregnancy or breast-feeding women, men have fertility requirements Patients within clinical trials or not more than 30 days

Ages Eligible for Study
-----------------
Minimum Age: 18 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: High dose group<br>Zoledronic acid 4 mg + 0.9% sodium chloride injection 100 ml intravenous drip more than 15 min, 28 days for a transfusion cycle , a total of six cycle，Radiotherapy dose: 30Gy/10f | Drug: Zoledronic acid<br>* Comparison the curative effect of the high does radiotherapy and low does therapy after use the Zoledronic acid<br>* Other names: Zometa;Radiation: Radiotherapy<br>* High dose：30Gy/10f Low dose：15Gy/5f<br>|
| Experimental: Low dose group<br>Zoledronic acid 4 mg + 0.9% sodium chloride injection 100 ml intravenous drip more than 15 min, 28 days for a transfusion cycle, a total of six cycle，Radiotherapy dose: 15Gy/5f | Drug: Zoledronic acid<br>* Comparison the curative effect of the high does radiotherapy and low does therapy after use the Zoledronic acid<br>* Other names: Zometa;Radiation: Radiotherapy<br>* High dose：30Gy/10f Low dose：15Gy/5f<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants reach objective response | Objective response is defined as the patients bone pain relief reach PR(Partial remission) or CR(Complete remission).and Objective response rate is defined as Objective response patients'percentage in total patients. Time evaluation points 1 month is the time after radiotherapy. | Up to 1 month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants occur bone pain recurrence at 1 to 12 month after radiotherapy. | Bone pain Recurrence is defined as the time of the original parts again pain and the VAS is more than 4 points. | every months up to the 12th month after treatment | 
| Pain relief time in/after treatment | Pain relief time is defined as the time of the VAS(Visual analogue scale) score reduce 2 points or the analgesic reduce 25% after the radiotherapy Time evaluation points :when patients in treatment ,we shall evaluate pain scores everyday ; when patients after treatment,we shall evluate pain scores every month. | everyday in treatment and every months up to 12 monthes | 
| Incidence of SRE(Skeletal-related events) again in Participants | Incidence of SRE again is defined as the Participants occur SRE events after treatment. Time evaluation points :When patients were after treat,we shall evaluate whether occur SRE again every month. | every monthes up to the 12th month after treatment | 
| Security of the therapy | Time evaluation points :when patients were in treatment ,we shall evaluate the toxicity everyday ; when patients were after treatment,we shall evluate toxicity every month. Method：Using RTOG acute radiation injury grading assessment and RTOG / EORTC late radiation injury grading for radiotherapy toxicity，CTCAE V3.0 for Adverse drug reactions. | everyday in treatment and every months up to the 12th month after treatment | 
| Percentage of the osteogenic and the osteolytic sites reach objective response |  | every months up to the 12th month | 
| Kaplan-Meier Estimates for Overall Survival after bone metastases |  | every months up to the 12th month after treatment | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
zoledronic acid, radiotherapy