Study of Thalidomide in Treatment of Advanced Nsclc (Dream-003)

Study Overview
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Brief Summary
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The study for innovative strategies is warranted in the treatment of advanced non-squamous NSCLC with epidermal growth factor receptor wild-type or unknown mutation status because the outcomes remain unsatisfactory for most patients. Maintenance treatment after first-line chemotherapy is a very interesting strategy that has been largely investigated in the last years. This study is to evaluate the efficacy and toxicity of thalidomide in combination with chemotherapy and as maintenance treatment in patients with advanced non-squamous NSCLC.

Detailed Description
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Lung cancer is the most common cancer and is the leading cause of cancer mortality in the world. Every year, more than one million people die from lung cancer in worldwide. NSCLC accounts for about 85% of all lung cancers diagnosis and continues to remain a major therapeutic challenge. Chemotherapeutic agents in the treatment of advanced NSCLC have reached a plateau of effectiveness when administered in the classic modality. In the first-line treatment of advanced non-squamous NSCLC with epidermal growth factor receptor wild-type, cisplatin plus pemetrexed is considered the best chemotherapeutic regimen. Recently, the PARAMOUNT trial has demonstrated that continuation maintenance with pemetrexed improves progression-free survival and overall survival after induction therapy with cisplatin plus pemetrexed in advanced non-squamous NSCLC with epidermal growth factor receptor wild-type. Bevacizumab, a pure humanized anti-VEGF monoclonal antibody (mAb) has improved the outcomes of chemotherapy alone when combined with chemotherapy as first-line therapy for advanced non-squamous NSCLC. A randomized phase Ⅲ trial named Eastern Cooperative Oncology Group E4559 has demonstrated that concurrent bevacizumab with chemotherapy followed by maintenance bevacizumab in previously untreated patients with advanced non-squamous NSCLC is associated with an increase in overall survival. In China, the cost of continuation maintenance with pemetrexed or bevacizumab is high in the current economic environment. Thalidomide is much cheaper than pemetrexed and bevacizumab, and has been shown to have activity in numerous malignancies. Although the exact anti-tumor mechanism is unknown, thalidomide exhibits both immuno-modulating and anti-angiogenic effects. Based on potentially synergistic mechanisms of action, thalidomide has the potential to enhance the activity of conventional chemotherapy. Results from previously published small studies in which thalidomide was given concurrently with conventional chemotherapy and was continued as maintenance therapy suggest that thalidomide might be effective in the treatment of patients with small cell lung cancer and NSCLC. Study and evaluation the efficacy and toxicity of thalidomide in combination with chemotherapy and as maintenance treatment in patients with advanced non-squamous NSCLC with epidermal growth factor receptor wild-type is necessary.

Official Title
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Study of Thalidomide With First-line Chemotherapy and as Maintenance Treatment of Advanced Nonsquamous NSCLC With Epidermal Growth Factor Receptor Wild-Type or Unknown Mutation Status: A Multicenter, Randomized, Prospective Clinical Trial

Conditions
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Advanced Nsclc

Intervention / Treatment
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* Drug: Thalidomide
* Drug: pemetrexed
* Drug: cisplatin
* Drug: carboplatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: stage Ⅳ non-squamous NSCLC with epidermal growth factor receptor wild-type or unknown mutation status confirmed by molecular biology and histology. age 18-70 years. Eastern Cooperative Oncology Group performance status of 0 or 1 and life expectancy greater than 3 months. no previous treatment with chemotherapy or radiotherapy adequate bone marrow, hepatic, and renal function measurable or evaluable disease informed consent negative pregnancy test and adequate contraception for the duration of treatment Exclusion Criteria: malignancy during the 5 years previous to the diagnosis of NSCLC (unless nonmelanoma skin cancer or early cervical cancer) surgery within 4 weeks history of major hemoptysis recent history of bleeding or thrombotic events brain metastasis uncontrolled hypertension ongoing therapeutic anticoagulation

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: P+Cisplatin/Carboplatin+T<br>Induction therapy (Platinum based chemotherapy combined with antiangiogenic therapy 4-6 cycles): Pemetrexed + Platinum + Thalidomide [pemetrexed (500mg/m^2)+cisplatin(75mg/m^2)or carboplatin(AUC=5) on day 1 of 21-days cycle, ivgtt +thalidomide 100-200mg/d ,oral, qn ] Continue maintenance therapy (It is defined when a drug included in the induction treatment is used as maintenance .Patients who had not progressed during induction phase will be in this phase): Thalidomide 100mg/d ,oral, qn, until either disease progression or unacceptable toxicity. | Drug: Thalidomide<br>* 100-200mg/d,oral ,qn<br>* Other names: H32026128;Drug: pemetrexed<br>* (500mg/m^2) on day 1 of 21-days cycle,ivgtt<br>* Other names: H20090232;Drug: cisplatin<br>* (75mg/m^2) on day 1 of 21-days cycle, ivgtt<br>* Other names: H20040813;Drug: carboplatin<br>* (AUC=5) on day 1 of 21-days cycle, ivgtt<br>* Other names: H20020180;|
| Experimental: P+Cisplatin/Carboplatin<br>Induction therapy ( Platinum based chemotherapy 4-6 cycles): Pemetrexed + Platinum [pemetrexed (500mg/m^2)+cisplatin(75mg/m^2)or carboplatin(AUC=5) on day 1 of 21-days cycle,ivgtt ] Maintenance therapy (It is defined when a drug included in the induction treatment is used as maintenance .Patients who had not progressed during induction phase will be in this phase): Pemetrexed (500mg/m^2) on day 1 of 21-days cycle, ivgtt.until either disease progression or unacceptable toxicity | Drug: pemetrexed<br>* (500mg/m^2) on day 1 of 21-days cycle,ivgtt<br>* Other names: H20090232;Drug: cisplatin<br>* (75mg/m^2) on day 1 of 21-days cycle, ivgtt<br>* Other names: H20040813;Drug: carboplatin<br>* (AUC=5) on day 1 of 21-days cycle, ivgtt<br>* Other names: H20020180;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| progression-free survival (PFS) | Addition of thalidomide to chemotherapy and as single maintenance treatment is associated with similar PFS with Control Arm. | 2 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| objective response rate(ORR) | Response rates are similar in the two treatment groups | 2 years | 
| weight | Thalidomide can increase the weight of the patient | 2 years | 
| vascular endothelial growth factor (VEGF) VEGF | Thalidomide can decrease the level of VEGF | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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thalidomide, pemetrexed, nsclc, maintenance treatment