Clinical Trials /

Pemetrexed Combined With Synchronous Gefitinib as Adjuvent Therapy in Patient With EGFR Mutant Lung Adenocarcinoma

NCT02518802

Description:

This randomized phase III trial is studying gefitinib and synchronous pemetrexed/cisplatin chenmotherapy to see how well it works compared to pemetrexed/cisplatin chenmotherapy alone in treating patients who have undergone surgery for stage II-IIIA(N1-N2) lung adenocarcinoma with EGFR activating mutation in Asian population.

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

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: Pemetrexed Combined With Synchronous Gefitinib as Adjuvent Therapy in Patient With EGFR Mutant Lung Adenocarcinoma
  • Official Title: Pemetrexed Disodium and Cisplatin Chemotherapy Combined With Synchronous Gefitinib vs Chemotherapy Alone as Adjuvent Therapy in Patient With Stage II-IIIA, Epidermal Growth Factor Receptor Mutant Expressing Lung Adenocarcinoma

Clinical Trial IDs

  • ORG STUDY ID: W-TONG002
  • NCT ID: NCT02518802

Conditions

  • Lung Neoplasms

Interventions

DrugSynonymsArms
GefitinibIressaSynchronous therapy
PemetrexedAlimtaSynchronous therapy

Purpose

This randomized phase III trial is studying gefitinib and synchronous pemetrexed/cisplatin chenmotherapy to see how well it works compared to pemetrexed/cisplatin chenmotherapy alone in treating patients who have undergone surgery for stage II-IIIA(N1-N2) lung adenocarcinoma with EGFR activating mutation in Asian population.

Detailed Description

      Adjuvant cisplatin-based chemotherapy is recommended for routine use in patients with stages
      IIA, IIB, and IIIA non-small cell lung cancer (NSCLC) after complete resection. Cisplatin and
      pemetrexed combination is the standard regimen for lung adenocarcinoma in adjuvant setting.
      The BR. 19 trial reported adjuvant gefitinib after complete resection of early stage
      NSCLC(stage IB 49%, II 38%, III 13%) did not confer disease free survival(DFS) or overall
      survival(OS) advantage in overall population. While the median gefitinib treatment time is
      only 4.8 months. There are only 76 patients with EGFR mutations included in this analysis.
      The study closed prematurely in 2005.

      Activating somatic mutations of the tyrosine kinase domain of epidermal growth factor
      receptor (EGFR) have been characterized in a subset of patients with advanced NSCLC.The EGFR
      mutation rate was 30% in Chinese NSCLC. Patients harboring these mutations in their tumors
      show excellent response to EGFR tyrosine kinase inhibitors (EGFR-TKIs). This randomized phase
      III trial is studying gefitinib and synchronous pemetrexed/cisplatin chenmotherapy to see how
      well it works compared to pemetrexed/cisplatin chenmotherapy alone in treating patients who
      have undergone surgery for stage II-IIIA(N1-N2) lung adenocarcinoma with EGFR activating
      mutation in Asian population.
    

Trial Arms

NameTypeDescriptionInterventions
Synchronous therapyExperimental'Gefitinib and Pemetrexed' Synchronous use of Gefitinib for 2 years during or after chemotherapy with Pemetrexed plus Cisplatin regimen. Gefitinb, 250mg per day,take orally for 2 years. Pemetrexed, 500mg/m2, day 1; Cisplatin 75mg/m2, day 1. Three weeks as a cycle. Four cycles in total.
  • Gefitinib
  • Pemetrexed
ChemotherapyActive ComparatorPemetrexed: Pemetrexed, 500mg/m2, day 1; Cisplatin 75mg/m2, day 1. Three weeks as a cycle. Four cycles in total.
  • Pemetrexed

Eligibility Criteria

        Inclusion Criteria:

          -  Written informed consent provided.

          -  Males or females aged ≥18 years, < 70 years.

          -  Able to comply with the required protocol and follow-up procedures, and able to
             receive oral medications.

          -  Target population is completely resected pathological stage II-IIIA(N1-N2) NSCLC with
             EGFR exon 19 deletions and exon 21 L858R activating mutation.

          -  Patient who can start the investigational therapy within 3-6 weeks after the complete
             resection

          -  ECOG performance status 0-1.

          -  Life expectancy ≥12 weeks.

          -  Adequate hematological function: Absolute neutrophil count (ANC) ≥2.0 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, or ≥ 60 ml/min.

          -  Female subjects should not be pregnant or breast-feeding.

        Exclusion Criteria:

          -  Known severe hypersensitivity to gefitinib or any of the excipients of this product.

          -  Known severe hypersensitivity to pre-medications required for treatment with cisplatin
             / vinorelbine doublet chemotherapy.

          -  Inability to comply with protocol or study procedures.

          -  A serious concomitant systemic disorder that, in the opinion of the investigator,
             would compromise the patient's ability to complete the study.

          -  A serious cardiac condition, such as myocardial infarction within 6 months, angina, or
             heart disease.

          -  Interstitial pneumonia.

          -  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).

          -  Patients with prior radiotherapy

          -  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).

          -  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.

          -  Patient who has active serious infection (e.g. pyrexia of or 38.0℃ over)

          -  Patients who harbouring exon 20 T790M mutation.
      
Maximum Eligible Age:70 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Disease free survival
Time Frame:From date of randomization to the first documented disease progression or death, whichever occurs first, assessed up to 3 and 5 years.
Safety Issue:
Description:To evaluate the disease free survival of synchronous therapy versus combination of Pemetrexed plus Cisplatin as adjuvant treatment for pathological stage II-IIIA(N1-N2) lung adenocarcinoma with EGFR mutation.Disease free survival (DFS)- defined as the time from randomization to the first documented disease progression or death, whichever occurs first.

Secondary Outcome Measures

Measure:Overall survival
Time Frame:From date of randomization to the first documented death, assessed up to 5 years.
Safety Issue:
Description:To evaluate the overall survival of synchronous therapy versus combination of Pemetrexed plus Cisplatin as adjuvant treatment for stage II-IIIA(N1-N2) lung adenocarcinoma with EGFR mutation.
Measure:Number of Participants with Adverse Events
Time Frame:In the period of Gefitinib 250 mg/day oral daily for 24 months. Pemetrexed 500 mg/m2 intravenous infusion on day 1, Cisplatin 75 mg/m2 on day 1 for 4 cycles.
Safety Issue:
Description:The safety and tolerability profile of gefitinib at a 250 mg daily dose relative to that of Chemotherapy.
Measure:Quality of life
Time Frame:In the period of Gefitinib 250 mg/day oral daily for 24 months. Pemetrexed 500 mg/m2 intravenous infusion on day 1, Cisplatin 75 mg/m2 on day 1 for 4 cycles.
Safety Issue:
Description:Quality of life as measured by the total score and Trial Outcome Index (TOI) of the Functional Assessment of Cancer Therapy - Lung Cancer (FACT-L) questionnaire.

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Tang-Du Hospital

Trial Keywords

  • Gefitinib
  • Pemetrexed
  • Synchronous therapy
  • Adjuvent therapy

Last Updated

August 5, 2015