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

Advanced Nsclc Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03062800
• Other study ID #: Dream-003
• Status: Recruiting
• Phase: Phase 2
• Start date: December 2016
• Est. completion date: November 2021

Study information

• Verified date: June 2019
• Source: Qilu Hospital of Shandong University
• Contact: Xiuwen Wang, MD.PhD
• Phone: +86 13791123979
• Email: wangxiuwen[@]medmail.com.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 232
• Est. completion date: November 2021
• Est. primary completion date: December 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

1. stage ? non-squamous NSCLC with epidermal growth factor receptor wild-type or unknown mutation status confirmed by molecular biology and histology.

2. age 18-70 years.

3. Eastern Cooperative Oncology Group performance status of 0 or 1 and life expectancy greater than 3 months.

4. no previous treatment with chemotherapy or radiotherapy

5. adequate bone marrow, hepatic, and renal function

6. measurable or evaluable disease

7. informed consent

8. negative pregnancy test and adequate contraception for the duration of treatment

Exclusion Criteria:

1. malignancy during the 5 years previous to the diagnosis of NSCLC (unless nonmelanoma skin cancer or early cervical cancer)

2. surgery within 4 weeks

3. history of major hemoptysis

4. recent history of bleeding or thrombotic events

5. brain metastasis

6. uncontrolled hypertension

7. ongoing therapeutic anticoagulation

Related Conditions & MeSH terms

• Advanced Nsclc

Intervention

Drug:
• Thalidomide
100-200mg/d,oral ,qn
• pemetrexed
(500mg/m^2) on day 1 of 21-days cycle,ivgtt
• cisplatin
(75mg/m^2) on day 1 of 21-days cycle, ivgtt
• carboplatin
(AUC=5) on day 1 of 21-days cycle, ivgtt

Locations

Country	Name	City	State
China	Qilu hospital of Shandong University	Jinan	Shandong

Sponsors (1)

Lead Sponsor	Collaborator
Qilu Hospital of Shandong University

Country where clinical trial is conducted

China, 

References & Publications (6)

Gridelli C, Maione P, Rossi A. The PARAMOUNT trial: a phase III randomized study of maintenance pemetrexed versus placebo immediately following induction first-line treatment with pemetrexed plus cisplatin for advanced nonsquamous non-small cell lung cancer. Rev Recent Clin Trials. 2013 Mar;8(1):23-8. — View Citation

Iwasaki A, Kuwahara M, Yoshinaga Y, Shirakusa T. Basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) levels, as prognostic indicators in NSCLC. Eur J Cardiothorac Surg. 2004 Mar;25(3):443-8. — View Citation

Lee SM, James L, Buchler T, Snee M, Ellis P, Hackshaw A. Phase II trial of thalidomide with chemotherapy and as maintenance therapy for patients with poor prognosis small-cell lung cancer. Lung Cancer. 2008 Mar;59(3):364-8. Epub 2007 Oct 24. — View Citation

Sandler A, Yi J, Dahlberg S, Kolb MM, Wang L, Hambleton J, Schiller J, Johnson DH. Treatment outcomes by tumor histology in Eastern Cooperative Group Study E4599 of bevacizumab with paclitaxel/carboplatin for advanced non-small cell lung cancer. J Thorac Oncol. 2010 Sep;5(9):1416-23. doi: 10.1097/JTO.0b013e3181da36f4. — View Citation

Villa C, Cagle PT, Johnson M, Patel JD, Yeldandi AV, Raj R, DeCamp MM, Raparia K. Correlation of EGFR mutation status with predominant histologic subtype of adenocarcinoma according to the new lung adenocarcinoma classification of the International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society. Arch Pathol Lab Med. 2014 Oct;138(10):1353-7. doi: 10.5858/arpa.2013-0376-OA. Epub 2014 Feb 26. — View Citation

Zhou S, Wang F, Hsieh TC, Wu JM, Wu E. Thalidomide-a notorious sedative to a wonder anticancer drug. Curr Med Chem. 2013;20(33):4102-8. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	objective response rate(ORR)	Response rates are similar in the two treatment groups	2 years
Secondary	weight	Thalidomide can increase the weight of the patient	2 years
Secondary	vascular endothelial growth factor (VEGF) VEGF	Thalidomide can decrease the level of VEGF	1 year

External Links

•   website of China Food and Drug Administrator