Erlotinib Versus Gemcitabine/Cisplatin as (Neo)Adjuvant Treatment in Non-small Cell Lung Cancer

NCT01407822 | Unknown Phase 2 DMC

• 2 other identifiers: CTONG 1103ML25304
• Study Type: interventional
• Target: 72
• Locations: 1 country
• Sites: 1

Brief Summary

Stage IIIA NSCLC represents a relatively heterogeneous group of pts with ipsilateral mediastinal (N2) lymph node involvement. The relative roles of treatment modalities are not clearly defined. Concurrent chemoradiation therapy remains an important treatment for stage IIIA disease, but its treatment-related life threatening toxicity limits its use. The EGFR tyrosine kinase inhibitor (TKI) may provide a dramatic response in pts with pulmonary adenocarcinoma carrying EGFR activating mutations in the metastatic setting. In the OPTIMAL study, first-line erlotinib versus carboplatin/GEM in advanced NSCLC pts with EGFR activating mutations, the primary analysis showed significantly prolonged progressive free survival (PFS) was with erlotinib vs carboplatin/GEM (p\<0.0001). The aim of this study is to investigate the efficacy and safety of erlotinib versus GEM plus cisplatin (GC) as neoadjuvant treatment in pts with stage IIIA-N2 NSCLC with EGFR activating mutations and to explore a new treatment strategy for this subset.

Conditions

Non-small Cell Lung Cancer

Keywords

Lung cancer; IIIA-N2; Neo-adjuvant treatment; EGFR mutations; Tyrosine kinase inhibitor

Outcome Measures

Primary Outcomes (1)

• The objective response rate (ORR) in neoadjuvant treatment

  To evaluate objective response rate (ORR) of Erlotinib versus combination of Gemcitabine plus Cisplatin as neoadjuvant treatment for stage IIIA- N2 NSCLC with EGFR activating mutation in exon 19 or 21.

  Tumor response will be evaluated after 6 weeks of induction treatment (during day 43 to day 49).

Secondary Outcomes (6)

• Complete resection rate

  The patients considered to be technically resectable will undergo resection. Lymph node downstage rate is depended on the pathology dignosis after surgery, an expected average of 8 weeks from randomization.

• Pathological complete response (pCR) rate

  The patients considered to be technically resectable will undergo resection. Lymph node downstage rate is depended on the pathology dignosis after surgery, an expected average of 8 weeks from randomization.

• Progression free survival（PFS）

  Pts after surgery will receive long-term follow-up including chest CT scan, abdominal ultrasound every 3 months, brain MRI every 6 months, bone scan (ECT) every 12 months for up to 2 years.

• 3 year overall survival (OS) rate

  Pts after surgery will receive long-term follow-up including chest CT scan, abdominal ultrasound every 3 months, brain MRI every 6 months, bone scan (ECT) every 12 months for up to 2 years.

• Number of Participants with Adverse Events

  During the neoadjuvant and adjuvant period, an expected average of 1 years from randomization.

Study Arms (2)

Erlotinib arm

EXPERIMENTAL

In the neo-adjuvant treatment phase, erlotinib 150 mg/day taken orally for 6 weeks(42 days).In the post-surgery phase, erlotinib 150mg/day taken orally for 1 year or till disease progression or unacceptable toxicity.

Drug: Erlotinib

Chemo arm

ACTIVE COMPARATOR

In the neo-adjuvant treatment phase, patient will receive gemcitabine 1250mg/m2 IV on day 1 and day 8, and cisplatin 75mg/m2 on day 1 of a 3-week schedule for 2 cycles. In the post-surgery phase, Gemcitabine 1250mg/m2 IV on day 1 and day 8, and cisplatin 75mg/m2 on day 1 of a 3-week schedule for 2 cycles or till disease progression or unacceptable toxicity.

Drug: Gemcitabine/cisplatin

Interventions

Erlotinib DRUG

In the neo-adjuvant treatment phase, erlotinib 150 mg/day taken orally for 6 weeks(42 days).In the post-surgery phase, erlotinib 150mg/day taken orally for 1 year or till disease progression or unacceptable toxicity.

Also known as: Tarceva

Erlotinib arm

Gemcitabine/cisplatin DRUG

In the neo-adjuvant treatment phase, patient will receive gemcitabine 1250mg/m2 IV on day 1 and day 8, and cisplatin 75mg/m2 on day 1 of a 3-week schedule for 2 cycles. In the post-surgery phase, Gemcitabine 1250mg/m2 IV on day 1 and day 8, and cisplatin 75mg/m2 on day 1 of a 3-week schedule for 2 cycles or till disease progression or unacceptable toxicity.

Also known as: Gemzar/cisplatin

Chemo arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent provided.
• Males or females aged ≥18 years.
• Able to comply with the required protocol and follow-up procedures, and able to receive oral medications.
• Pathologically diagnosed of non-small cell lung cancer.
• Diagnosed as stage IIIA- N2.The diagnosis standard of N2 is as below: Pts with resectable stage IIIA-N2 NSCLC confirmed by mediastinoscopy or EBUS or PET/CT.
• EGFR activating mutation in exon 19 or 21 by the biopsy of primary tumor or N2 lymph node.
• Measurable disease must be characterized according to RECIST 1.1 criteria.
• Measurable lesions are defined as those that can be accurately measured in at least one dimension (longest diameter to be recorded) as ≥ 10mm by spiral CT or MRI scan. The measurable criteria of lymph node is the short axis ≥ 15 mm.
• ECOG performance status 0-1.
• Life expectancy ≥12 weeks.
• Adequate hematological function:Absolute neutrophil count (ANC) ≥1.5 x 109/L, and Platelet count ≥100 x 109/L, and Hemoglobin ≥9 g/dL (may be transfused to maintain or exceed this level).
• Adequate liver function: Total bilirubin ≤ 1.5 x upper limit of normal (ULN);Aspartate aminotransferase (AST), alanine aminotransferase (ALT) ≤ 2.5 x ULN in subjects without liver metastases; ≤ 5 x ULN in subjects with liver metastases.
• Adequate renal function:Serum creatinine ≤ 1.25 x ULN, and creatinine clearance ≥ 60 ml/min.
• Female subjects should not be pregnant or breast-feeding.

You may not qualify if:

• Patients with prior exposure to agents directed at the HER axis (e.g. erlotinib, gefitinib, cetuximab, trastuzumab).
• Patients with prior chemotherapy or therapy with systemic anti-tumour therapy (e.g. monoclonal antibody therapy).
• Resection of primary malignancy.
• EGFR mutation (exon 19 or 21) negative or unknown.
• Uncontrolled central nervous system (CNS) metastasis.
• History of another malignancy in the last 5 years with the exception of the following:Other malignancies cured by surgery alone and having a continuous disease-free interval of 5 years are permitted; Cured basal cell carcinoma of the skin and cured in situ carcinoma of the uterine cervix are permitted.
• Any unstable systemic disease (including active infection, uncontrolled hypertension, unstable angina, congestive heart failure, myocardial infarction within the previous year, serious cardiac arrhythmia requiring medication, hepatic, renal, or metabolic disease).
• Known hypersensitivity to Tarceva or gemcitabine or cisplatin.
• Eye inflammation or eye infection not fully treated or conditions predisposing the subject to this.
• Evidence of any other disease, neurological or metabolic dysfunction, physical examination or laboratory finding giving reasonable suspicion of a disease or condition that contraindicated the use of an investigational drug or puts the subject at high risk for treatment-related complications.

Sponsors & Collaborators

• Guangdong Association of Clinical Trials: lead
• Guangdong Provincial People's Hospital: collaborator
• Tianjin Medical University Cancer Institute and Hospital: collaborator
• Jilin Provincial Tumor Hospital: collaborator
• Jiangsu Cancer Institute & Hospital: collaborator
• Zhejiang Cancer Hospital: collaborator
• Peking University Cancer Hospital & Institute: collaborator
• Sun Yat-sen University: collaborator
• West China Hospital: collaborator
• The First Affiliated Hospital of Dalian Medical University: collaborator
• Peking University People's Hospital: collaborator
• Xi'an Jiaotong University: collaborator
• Shanghai Zhongshan Hospital: collaborator
• Guangzhou General Hospital of Guangzhou Military Command: collaborator
• The First Affiliated Hospital of Guangzhou Medical University: collaborator
• Fujian Medical University Union Hospital: collaborator
• Linyi Tumour Hospital: collaborator
• Northern Jiangsu People's Hospital: collaborator

Study Sites (1)

Guangdong General Hospital

Guangzhou, Guangdong, 510080, China

Location

Related Publications (6)

• 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.

  PMID: 18757336 BACKGROUND

• 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.

  PMID: 17548126 BACKGROUND

• Haura EB, Sommers E, Song L, Chiappori A, Becker A. A pilot study of preoperative gefitinib for early-stage lung cancer to assess intratumor drug concentration and pathways mediating primary resistance. J Thorac Oncol. 2010 Nov;5(11):1806-14. doi: 10.1097/JTO.0b013e3181f38f70.

  PMID: 20881637 BACKGROUND

• Rizvi NA, Rusch V, Pao W, Chaft JE, Ladanyi M, Miller VA, Krug LM, Azzoli CG, Bains M, Downey R, Flores R, Park B, Singh B, Zakowski M, Heelan RT, Shen R, Kris MG. Molecular characteristics predict clinical outcomes: prospective trial correlating response to the EGFR tyrosine kinase inhibitor gefitinib with the presence of sensitizing mutations in the tyrosine binding domain of the EGFR gene. Clin Cancer Res. 2011 May 15;17(10):3500-6. doi: 10.1158/1078-0432.CCR-10-2102. Epub 2011 May 10.

  PMID: 21558399 BACKGROUND

• Zhong WZ, Yan HH, Chen KN, Chen C, Gu CD, Wang J, Yang XN, Mao WM, Wang Q, Qiao GB, Cheng Y, Xu L, Wang CL, Chen MW, Kang XZ, Yan WP, Liao RQ, Yang JJ, Zhang XC, Liu SY, Zhou Q, Wu YL. Erlotinib versus gemcitabine plus cisplatin as neoadjuvant treatment of stage IIIA-N2 EGFR-mutant non-small-cell lung cancer: final overall survival analysis of the EMERGING-CTONG 1103 randomised phase II trial. Signal Transduct Target Ther. 2023 Feb 24;8(1):76. doi: 10.1038/s41392-022-01286-3.

  PMID: 36823150 DERIVED

• Zhong WZ, Chen KN, Chen C, Gu CD, Wang J, Yang XN, Mao WM, Wang Q, Qiao GB, Cheng Y, Xu L, Wang CL, Chen MW, Kang X, Yan W, Yan HH, Liao RQ, Yang JJ, Zhang XC, Zhou Q, Wu YL. Erlotinib Versus Gemcitabine Plus Cisplatin as Neoadjuvant Treatment of Stage IIIA-N2 EGFR-Mutant Non-Small-Cell Lung Cancer (EMERGING-CTONG 1103): A Randomized Phase II Study. J Clin Oncol. 2019 Sep 1;37(25):2235-2245. doi: 10.1200/JCO.19.00075. Epub 2019 Jun 13.

  PMID: 31194613 DERIVED

Related Links

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

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Lung Neoplasms

Interventions

Erlotinib Hydrochloride; Gemcitabine; Cisplatin

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Study Officials

• Yi-Long WU, MD

  Guangdong Lung Cancer Institute

  PRINCIPAL INVESTIGATOR

• Xue-Ning YANG, MD

  Guangdong Provincial People's Hospital

  STUDY CHAIR

• Wen-Zhao ZHONG, MD

  Guangdong Lung Cancer Institute

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Dr

Study Record Dates

• First Submitted: July 26, 2011
• First Posted: August 2, 2011
• Study Start: December 5, 2011
• Primary Completion: April 24, 2018
• Study Completion: December 1, 2022
• Last Updated: September 11, 2018

Record last verified: 2018-09

Locations

CN (1)