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

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2013 by Guangdong Association of Clinical Trials
Sponsor:
Collaborators:
Guangdong General Hospital
Tianjin Medical University Cancer Institute and Hospital
Jilin Provincial Tumor Hospital
Jiangsu Cancer Institute & Hospital
Zhejiang Cancer Hospital
Beijing Cancer Hospital
Sun Yat-sen University
West China Hospital
The First Affiliated Hospital of Dalian Medical University
Peking University People's Hospital
Xi’an Jiaotong University College of Medicine
Shanghai Zhongshan Hospital
Guangzhou General Hospital of Guangzhou Military Command
The First Affiliated Hospital of Guangzhou Medical University
Shanghai Chest Hospital
Fujian Medical University
Information provided by (Responsible Party):
Yi-Long Wu, Guangdong Association of Clinical Trials
ClinicalTrials.gov Identifier:
NCT01407822
First received: July 26, 2011
Last updated: September 5, 2013
Last verified: September 2013
  Purpose

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.


Condition Intervention Phase
Non-small Cell Lung Cancer
Drug: Erlotinib
Drug: Gemcitabine/cisplatin
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A National, Multi Center, Randomized, Open-label, Phase II Trial of Erlotinib Versus Combination of Gemcitabine Plus Cisplatin as (Neo)Adjuvant Treatment in Stage IIIA-N2 Non-small-cell Lung Cancer With Sensitizing EGFR Mutation in Exon 19 or 21(EMERGING)

Resource links provided by NLM:


Further study details as provided by Guangdong Association of Clinical Trials:

Primary Outcome Measures:
  • The objective response rate (ORR) in neoadjuvant treatment [ Time Frame: Tumor response will be evaluated after 6 weeks of induction treatment (during day 43 to day 49). ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Complete resection rate [ Time Frame: 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. ] [ Designated as safety issue: No ]
    To evaluate radical resection rate of two groups.

  • Pathological complete response (pCR) rate [ Time Frame: 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. ] [ Designated as safety issue: No ]
    To evaluate the pathological complete response (pCR) rate of two groups.

  • Progression free survival(PFS) [ Time Frame: 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. ] [ Designated as safety issue: No ]
    To evaluate Progressive Free Survival (PFS) of two groups.

  • 3 year overall survival (OS) rate [ Time Frame: 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. ] [ Designated as safety issue: No ]
    To evaluate the 3 year overall survival (OS) rate of two groups.The third year after surgery is survival follow-up.

  • Number of Participants with Adverse Events [ Time Frame: During the neoadjuvant and adjuvant period, an expected average of 1 years from randomization. ] [ Designated as safety issue: No ]
    To evaluate the safety profile(Number of Participants with Adverse Events) of two group.

  • Quality of Life (QOL) [ Time Frame: During the neo-adjuvant treatment phase(1-42 days), surgery treatment phase and adjuvant phase, , an expected average of 1 years from randomization. ] [ Designated as safety issue: Yes ]
    To evaluate the Quality of Life (QOL) of two group


Estimated Enrollment: 90
Study Start Date: July 2011
Estimated Study Completion Date: March 2016
Estimated Primary Completion Date: March 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Erlotinib arm
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
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.
Other Name: Tarceva
Active Comparator: Chemo arm
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
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.
Other Name: Gemzar/cisplatin

Detailed Description:

Concurrent Chemoradiation therapy remain the standard treatment for stage IIIA disease, but its treatment-related life threaten toxicity limit its use for those pts.

Tarceva monotherapy have been demonstrated a significant improvement in overall survival and disease progression free survival when used for the treatment of patients with metastatic NSCLC, after failure of at least one prior chemotherapy regimen. It is well tolerated without the side effects usually associated with chemotherapy.

Based on the encouraging results reported from the SLCG phase II study reported the efficacy of Tarceva as first line treatment for metastatic NSCLC with EGFR mutation patients would prolong overall survival, delay disease progression and be well tolerated, mOS reached 27 months, ORR reached 71%. Besides, with different mechanism and more tolerable than chemo, Tarceva may provide an important treatment alternative for local advanced pts with EGFR mutation.

In IPASS study (gefitinib or carboplatin/paclitaxel in pulmonary adenocarcinoma as first line treatment), the subgroup of 261 patients who were positive for the epidermal growth factor receptor gene (EGFR) mutation, progression-free survival was significantly longer among those who received gefitinib than among those who received carboplatin-paclitaxel (hazard ratio for progression or death, 0.48; 95% CI, 0.36 to 0.64; P<0.001).

In OPTIMAL study (first-line erlotinib versus carboplatin/gemcitabine in Chinese advanced NSCLC patients with EGFR activating mutations), the primary analysis showed PFS was significantly prolonged with erlotinib vs carboplatin/paclitaxel(13.1months vs 4.6 months, HR 0.16 ; p<0.0001). The objective response rate was significantly improved with erlotinib vs carboplatin/paclitaxel (83% vs 36%, p=0.0000), as was the disease control rate (CR + PR + SD; 96 vs 82%; p=0.002).

The aim of this study is to investigate the efficacy and safety of Tarceva versus combination of Gemcitabine plus Cisplatin as neoadjuvant treatment in patients with stage IIIA- N2 NSCLC with EGFR activating mutation in exon 19 or 21.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01407822

Contacts
Contact: Yi-Long WU, MD +8620,83877855 syylwu@live.cn
Contact: Wen-Zhao ZHONG, MD 008618688389223 13609777314@163.com

Locations
China, Guangdong
Guangdong General Hospital Recruiting
Guangzhou, Guangdong, China, 510080
Contact: Xue-Ning YANG, MD       yangxuening@gmail.com   
Contact: Wen-zhao , ZHONG       13609777314@163.com   
Sponsors and Collaborators
Guangdong Association of Clinical Trials
Guangdong General Hospital
Tianjin Medical University Cancer Institute and Hospital
Jilin Provincial Tumor Hospital
Jiangsu Cancer Institute & Hospital
Zhejiang Cancer Hospital
Beijing Cancer Hospital
Sun Yat-sen University
West China Hospital
The First Affiliated Hospital of Dalian Medical University
Peking University People's Hospital
Xi’an Jiaotong University College of Medicine
Shanghai Zhongshan Hospital
Guangzhou General Hospital of Guangzhou Military Command
The First Affiliated Hospital of Guangzhou Medical University
Shanghai Chest Hospital
Fujian Medical University
Investigators
Principal Investigator: Yi-Long WU, MD Guangdong Lung Cancer Institute
Study Chair: Xue-Ning YANG, MD Guangdong General Hospital
Study Director: Wen-Zhao ZHONG, MD Guangdong Lung Cancer Institute
  More Information

Additional Information:
Publications:
Responsible Party: Yi-Long Wu, Dr, Guangdong Association of Clinical Trials
ClinicalTrials.gov Identifier: NCT01407822     History of Changes
Obsolete Identifiers: NCT01392404
Other Study ID Numbers: C-TONG 1103, ML25304
Study First Received: July 26, 2011
Last Updated: September 5, 2013
Health Authority: China: Ethics Committee

Keywords provided by Guangdong Association of Clinical Trials:
Lung cancer
IIIA-N2
Neo-adjuvant treatment
EGFR mutations
Tyrosine kinase inhibitor

Additional relevant MeSH terms:
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Gemcitabine
Cisplatin
Erlotinib
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Protein Kinase Inhibitors

ClinicalTrials.gov processed this record on October 01, 2014