Induction Erlotinib Therapy in Stage III A (N2) Non-Small Cell Lung Cancer (NSCLC)

Phase Ⅱ Study of Induction Erlotinib Therapy in Stage III A(N2) Non-small Cell Lung Cancer Proceeding to Mediastinoscopy/PET and Thoracotomy/Radiotherapy

The purpose of this study is to evaluate the value of induction Erlotinib therapy before thoracotomy or radiotherapy in ⅢA-N2 (confirmed by mediastinoscopy or PET) non-small cell lung cancer (NSCLC) selected by epidermal growth factor receptor (EGFR) gene analysis and initial to explore a new treatment strategy for ⅢA-N2 NSCLC.

Study Overview

• Status: Completed
• Conditions: Carcinoma, Non-Small-Cell Lung
• Intervention / Treatment: Drug: neoadjuvant erlotinib therapy; Drug: neoadjuvant gemcitabine/carboplatin therapy

Detailed Description

Stage IIIA non-small-cell lung cancer (NSCLC) is seen in a relatively heterogeneous group of patients with ipsilateral mediastinal (N2) lymph node involvement. The relative roles of different treatment modalities are not clear. Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) may result in dramatic responses in patients with pulmonary adenocarcinoma carrying EGFR activating mutations. In case reports, the efficacy of perioperative EGFR-TKI therapy in patients with locally advanced NSCLC harboring EGFR gene mutations was satisfactory. Although no prospective data support the use of EGFR-TKIs as induction therapy in stage IIIA-N2 NSCLC, their low toxicity profile and the possibility of a rapid tumor response suggests that prospective trials are required. Therefore, this study evaluated the value of induction erlotinib therapy in IIIA-N2 NSCLC selected by EGFR gene analysis and explored a new treatment strategy for this subset. Erlotinib specifically targets the EGFR TK domain, which is highly expressed and occasionally mutated in various forms of cancer. It binds in a reversible fashion to the adenosine triphosphate (ATP) binding site of the receptor.

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510080
      • Guangdong General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Written informed consent
• Histological or cytological documented
• Resectable NSCLC of stage IIIA-N2 confirmed by mediastinoscopy or PET
• Naive therapy NSCLC
• Candidates should be tolerated with induction therapy and thoracotomy with ECOG performance status 0-2, adequate haematological and Hepatic- renal function and qualified lung function
• Enough tissue samples to perform gene analysis

Exclusion Criteria:

• Small cell lung cancer
• Pregnant or breast-feeding women
• Any unstable systemic disease
• Patients with exposure to investigational drug therapy or other concurrent anticancer therapy outside of this trial

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Factorial Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: A; Erlotinib targeted NSCLC population based on EGFR gene analysis(EGFR gene status: activating mutation)	Drug: neoadjuvant erlotinib therapy; 150mg erlotinib taken once daily and continued uninterrupted for 42 days before evaluation/thoracotomy/radiotherapy.; Other Names: tarceva
Active Comparator: B; Non-erlotinib targeted NSCLC population based on EGFR gene analysis	Drug: neoadjuvant gemcitabine/carboplatin therapy; 3 cycles of neoadjuvant gemcitabine(1250mg/m2,d1,d8)/carboplatin(AUC=5,day1) chemotherapy before evaluation/thoracotomy/radiotherapy.; Other Names: gemzar

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Response to Neoadjuvant Erlotinib Therapy	a week after completion of the induction erlotinib therapy

Secondary Outcome Measures

Outcome Measure	Time Frame
disease free survival	every 3 months
overall survival	every 3 months
complete resection rate	7 days after thoractomy
Toxicity of Neoadjuvant Erlotinib Therapy and postoperative complications	one months after thoractomy

Collaborators and Investigators

• Sponsor: Guangdong Provincial People's Hospital
• Investigators: Principal Investigator: Yi-long WU, MD, Guangdong Lung Cancer Institute, Guangdong Lung Cancer Institute, Guangdong Academy of Medical Sciences; Study Chair: Xue-ning YANG, MD, Guangdong Lung Cancer Institute, Guangdong Lung Cancer Institute, Guangdong Academy of Medical Sciences; Study Director: Wen-zhao ZHONG, MD, Guangdong Lung Cancer Institute, Guangdong Lung Cancer Institute, Guangdong Academy of Medical Sciences

Publications and helpful links

General Publications

• Mok TS, Wu YL, Thongprasert S, Yang CH, Chu DT, Saijo N, Sunpaweravong P, Han B, Margono B, Ichinose Y, Nishiwaki Y, Ohe Y, Yang JJ, Chewaskulyong B, Jiang H, Duffield EL, Watkins CL, Armour AA, Fukuoka M. Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med. 2009 Sep 3;361(10):947-57. doi: 10.1056/NEJMoa0810699. Epub 2009 Aug 19.
• Wu YL, Zhong WZ, Li LY, Zhang XT, Zhang L, Zhou CC, Liu W, Jiang B, Mu XL, Lin JY, Zhou Q, Xu CR, Wang Z, Zhang GC, Mok T. Epidermal growth factor receptor mutations and their correlation with gefitinib therapy in patients with non-small cell lung cancer: a meta-analysis based on updated individual patient data from six medical centers in mainland China. J Thorac Oncol. 2007 May;2(5):430-9. doi: 10.1097/01.JTO.0000268677.87496.4c.
• Costa DB, Kobayashi S, Tenen DG, Huberman MS. Pooled analysis of the prospective trials of gefitinib monotherapy for EGFR-mutant non-small cell lung cancers. Lung Cancer. 2007 Oct;58(1):95-103. doi: 10.1016/j.lungcan.2007.05.017. Epub 2007 Jul 3.
• Takamochi K, Suzuki K, Sugimura H, Funai K, Mori H, Bashar AH, Kazui T. Surgical resection after gefitinib treatment in patients with lung adenocarcinoma harboring epidermal growth factor receptor gene mutation. Lung Cancer. 2007 Oct;58(1):149-55. doi: 10.1016/j.lungcan.2007.04.016. Epub 2007 Jun 4.
• Kappers I, Klomp HM, Burgers JA, Van Zandwijk N, Haas RL, van Pel R. Neoadjuvant (induction) erlotinib response in stage IIIA non-small-cell lung cancer. J Clin Oncol. 2008 Sep 1;26(25):4205-7. doi: 10.1200/JCO.2008.16.3709. No abstract available.
• Robinson LA, Wagner H Jr, Ruckdeschel JC; American College of Chest Physicians. Treatment of stage IIIA non-small cell lung cancer. Chest. 2003 Jan;123(1 Suppl):202S-220S. doi: 10.1378/chest.123.1_suppl.202s.
• Zhong W, Yang X, Yan H, Zhang X, Su J, Chen Z, Liao R, Nie Q, Dong S, Zhou Q, Yang J, Tu H, Wu YL. Phase II study of biomarker-guided neoadjuvant treatment strategy for IIIA-N2 non-small cell lung cancer based on epidermal growth factor receptor mutation status. J Hematol Oncol. 2015 May 17;8:54. doi: 10.1186/s13045-015-0151-3.

Study record dates

Study Major Dates

• Study Start: September 1, 2007
• Primary Completion (Actual): June 1, 2013
• Study Completion (Actual): June 1, 2013

Study Registration Dates

• First Submitted: January 14, 2008
• First Submitted That Met QC Criteria: January 14, 2008
• First Posted (Estimate): January 25, 2008

Study Record Updates

• Last Update Posted (Estimate): June 25, 2013
• Last Update Submitted That Met QC Criteria: June 23, 2013
• Last Verified: June 1, 2013

More Information

Terms related to this study

• Keywords: tyrosine kinase inhibitor; Neoadjuvant Therapy; Carcinoma, Non-Small-Cell Lung; Genes, erbB-1
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Protein Kinase Inhibitors; Gemcitabine; Carboplatin; Erlotinib Hydrochloride
• Other Study ID Numbers: CSLC-0702; tarceva-123456-1