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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)


Phase 2/Phase 3
18 Years
N/A
Open (Enrolling)
Both
Non-small Cell Lung Cancer

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Trial Information

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)


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.


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.

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

The objective response rate (ORR) in neoadjuvant treatment

Outcome Description:

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.

Outcome Time Frame:

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

Safety Issue:

No

Principal Investigator

Yi-Long WU, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Guangdong Lung Cancer Institute

Authority:

China: Ethics Committee

Study ID:

C-TONG 1103

NCT ID:

NCT01407822

Start Date:

July 2011

Completion Date:

March 2016

Related Keywords:

  • Non-Small Cell Lung Cancer
  • Lung cancer
  • IIIA-N2
  • Neo-adjuvant treatment
  • EGFR mutations
  • Tyrosine kinase inhibitor
  • Carcinoma, Non-Small-Cell Lung
  • Lung Neoplasms

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