The Optimal Intervention Time of Radiotherapy for Oligometastatic Stage IV Non-small Cell Lung Cancer（NSCLC）

Study Overview
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Brief Summary
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This study evaluates the optimal intervention time of radiotherapy for oligometastatic stage iv lung cancer.

Official Title
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The Prospective,Multicenter,Randomized Controlled Clinical Study of the Optimal Intervention Time of Radiotherapy for Oligometastatic Stage IV Non-small Cell Lung Cancer（NSCLC）

Conditions
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Oligo-metastatic Stage IV Non-small Cell Lung Cancer

Intervention / Treatment
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* Radiation: concurrent chemoradiotherapy
* Drug: Docetaxel
* Drug: pemetrexed
* Drug: Cisplatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18 to 75 years old , male or female Pathologically or cytologically proven oligometastatic stage IV NSCLC non-small cell lung cancer（NSCLC） Primary tumors can be measured Distant organ metastases number ≤ 5 Karnofsky score >70,Zubrod performance status 0-1 Estimated life expectancy of at least 12 weeks reproductive age women should ensure that before entering the study period contraception Hemoglobin≥10.0g/dL,WBC≥ 4000 cells/mm³,Platelet count≥100,000 cells/mm³ Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 2.5 times upper limit of normal,bilirubin normal Creatinine normal OR creatinine clearance ≥ 60 mL/min Patients have good compliance to treatment and follow-up of acceptance. Exclusion Criteria: Allergic to pemetrexed, cisplatin, docetaxel and contrast medium Distant metastases organs > 5 The primary tumor or lymph node already received surgical treatment (except for biopsy) Patient who received radiotherapy for primary tumor or lymph node Patient who received the the epidermal growth factor targeted therapy Patient who received chemotherapy or immunotherapy Patient who suffered from other malignant tumor Patient who have taken other drug test within 1 month Pregnant woman or Lactating Women and Women in productive age who refuse to take contraception in observation period Subject with a severe allergic history or idiosyncratic Subject with severe pulmonary and cardiopathic disease history Refuse or incapable to sign the informed consent form of participating this trial Drug abuse or alcohol addicted Subject with a Personality or psychiatric diseases, people with no legal capacity or people with limited capacity for civil conduct

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A<br>Patients receive concurrent chemoradiotherapy at first。Patients also receive chemotherapy every 3-4 weeks for two cycles after concurrent chemoradiotherapy. chemotherapy：（1） squamous cell carcinoma：Docetaxel 60mg/m2 d1+Cisplatin 25mg/m2 d1-3.（2）non squamous cell carcinoma： pemetrexed 500mg/m2 d1+Cisplatin 25mg/m2 d1-3. | Radiation: concurrent chemoradiotherapy<br>* Radiation（image-guided radiotherapy）：（1）primary tumors≤3cm，Hypofractionated radiation therapy，accumulated dose BED ≥80Gy （central lung cancer），BED ≥100Gy（Peripheral lung cancer）.（2）primary tumors>3cm，conventional fractionated radiotherapy，accumulated dose BED=60-66Gy/30-33f.（3） regional lymph node:conventional fractionated radiotherapy，accumulated dose BED=60-66Gy/30-33f.（4） Brain metastases： whole brain radiation therapy，36Gy/12f,Intracranial metastases，48Gy/12f.（5） bone metastasis：36 Gy/12f.<br>Drug: Docetaxel<br>* Docetaxel:60mg/m2 d1,Given IV<br>Drug: pemetrexed<br>* pemetrexed: 500mg/m2 d1,Given IV<br>Drug: Cisplatin<br>* Cisplatin：25mg/m2 d1-3，Given IV<br>|
| Active Comparator: Arm B<br>Patients receive neoadjuvant chemotherapy every 3-4 weeks for two cycles at first.Patients then receive concurrent chemoradiotherapy after neoadjuvant chemotherapy. chemotherapy：（1） squamous cell carcinoma：Docetaxel 60mg/m2 d1+Cisplatin 25mg/m2 d1-3.（2）non squamous cell carcinoma： pemetrexed 500mg/m2 d1+Cisplatin 25mg/m2 d1-3. | Radiation: concurrent chemoradiotherapy<br>* Radiation（image-guided radiotherapy）：（1）primary tumors≤3cm，Hypofractionated radiation therapy，accumulated dose BED ≥80Gy （central lung cancer），BED ≥100Gy（Peripheral lung cancer）.（2）primary tumors>3cm，conventional fractionated radiotherapy，accumulated dose BED=60-66Gy/30-33f.（3） regional lymph node:conventional fractionated radiotherapy，accumulated dose BED=60-66Gy/30-33f.（4） Brain metastases： whole brain radiation therapy，36Gy/12f,Intracranial metastases，48Gy/12f.（5） bone metastasis：36 Gy/12f.<br>Drug: Docetaxel<br>* Docetaxel:60mg/m2 d1,Given IV<br>Drug: pemetrexed<br>* pemetrexed: 500mg/m2 d1,Given IV<br>Drug: Cisplatin<br>* Cisplatin：25mg/m2 d1-3，Given IV<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| short-term effects（The response rate，RR） | Response Evaluation Criteria In Solid Tumors (RECIST) | 3 months after the end of the treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PFS（progression-free survival） |  | up to 3 years | 
| Quality of life (QOL) | Quality of life (QOL) as measured by the Functional Assessment of Cancer Therapy-Trial Outcome Index (FACT-TOI) and lung cancer subscale (LCS) | up to 3 years | 
| esophagitis and pneumonitis | Grade 3-5 esophagitis and pneumonitis adverse events as assessed by NCI Common Toxicity Criteria for Adverse Effects (CTCAE) v3.0 | up to 3 years | 
| Other grade 3-5 adverse events | Other grade 3-5 adverse events as assessed by NCI CTCAE v3.0 | up to 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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intervention time, radiotherapy, oligometastatic, non-small cell lung cancer