Clinical Trials /

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

NCT01407822

Description:

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.

Related Conditions:
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 2/Phase 3

Trial Eligibility

Document

Title

  • Brief Title: Erlotinib Versus Gemcitabine/Cisplatin as (Neo)Adjuvant Treatment in Non-small Cell Lung Cancer
  • Official Title: A National, Multi Center, Randomized, Open-label, Phase II Trial of Erlotinib Versus Combination of GC as (Neo)Adjuvant Treatment in Stage IIIA-N2 NSCLC With Sensitizing EGFR Mutation in Exon 19 or 21(EMERGING)

Clinical Trial IDs

  • ORG STUDY ID: CTONG 1103
  • SECONDARY ID: ML25304
  • NCT ID: NCT01407822
  • NCT ALIAS: NCT01392404

Conditions

  • Non-small Cell Lung Cancer

Interventions

DrugSynonymsArms
ErlotinibTarcevaErlotinib arm
Gemcitabine/cisplatinGemzar/cisplatinChemo arm

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.

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.
    

Trial Arms

NameTypeDescriptionInterventions
Erlotinib armExperimentalIn 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.
  • Erlotinib
Chemo armActive ComparatorIn 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.
  • Gemcitabine/cisplatin

Eligibility 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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure: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).
Safety Issue:
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.

Secondary Outcome Measures

Measure: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.
Safety Issue:
Description:To evaluate radical resection rate of two groups.
Measure: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.
Safety Issue:
Description:To evaluate the pathological complete response (pCR) rate of two groups.
Measure: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.
Safety Issue:
Description:To evaluate Progressive Free Survival (PFS) of two groups.
Measure: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.
Safety Issue:
Description:To evaluate the 3 year overall survival (OS) rate of two groups.The third year after surgery is survival follow-up.
Measure:Number of Participants with Adverse Events
Time Frame:During the neoadjuvant and adjuvant period, an expected average of 1 years from randomization.
Safety Issue:
Description:To evaluate the safety profile(Number of Participants with Adverse Events) of two group.
Measure: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.
Safety Issue:
Description:To evaluate the Quality of Life (QOL) of two group

Details

Phase:Phase 2/Phase 3
Primary Purpose:Interventional
Overall Status:Active, not recruiting
Lead Sponsor:Guangdong Association of Clinical Trials

Trial Keywords

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

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