Clinical Trials /

Gefitinib Combined With Chemotherapy or Antiangiogensis in Patients With Bim Deletion or Low EGFR Mutation Abundance

NCT02930954

Description:

This is a single arm phase II clinical trial, which aims to evaluate the effectiveness of combination of gefitinib and doublet chemotherapy or antiangiogenesis in advanced non-small cell lung cancer patients with EGFR activating mutation, accompanied with Bim deletion or low activating EGFR mutation abundance.

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

Unknown status

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Gefitinib Combined With Chemotherapy or Antiangiogensis in Patients With Bim Deletion or Low EGFR Mutation Abundance
  • Official Title: Combination of Gefitinib With Chemotherapy or Anti-angiogenesis as 1st Line Treatment in Advanced NSCLC Patients Detected With Bim Deletion or Low EGFR Activating Mutation Abundance

Clinical Trial IDs

  • ORG STUDY ID: FK1408
  • NCT ID: NCT02930954

Conditions

  • Non-small-cell Lung Cancer

Interventions

DrugSynonymsArms
GefitinibIressaGefitinib single agent
pemetrexed or gemcitabine plus carboplatin,Alimita or GimzaGefitinib combined with chemotherapy
bevacizumabGefitinib combined with antiangiogenesis

Purpose

This is a single arm phase II clinical trial, which aims to evaluate the effectiveness of combination of gefitinib and doublet chemotherapy or antiangiogenesis in advanced non-small cell lung cancer patients with EGFR activating mutation, accompanied with Bim deletion or low activating EGFR mutation abundance.

Detailed Description

      BIM deletion polymorphism and low EGFR mutation abundance were poor clinical response markers
      to EGFR-TKIs in NSCLC patients who had EGFR mutations.This is a phase II clinical trial to
      investigate the efficacy of combination treatment for patients harboring risk factors.

      Advanced EGFR mutated NSCLC Patients with Bim deletion or EGFR low mutation abundance were
      randomizely divided into three treatment groups:

      A:Gefitinib 250mg Qd B:Gefitinib 250mg Qd combined with doublet chemotherapy: Pemetrexed
      (500mg/m²day 1 intravenously) plus carboplatin (AUC=5,day 1,intravenously) every 21 days,
      Gemcitabine (1000 mg/m² days 1, day8, intravenously) plus carboplatin (AUC=5,day
      1,intravenously) every 21 days C:Gefitinib 250mg Qd combined with bevacizumab 7.5mg/kg
      intravenously per 21 days.
    

Trial Arms

NameTypeDescriptionInterventions
Gefitinib single agentActive ComparatorAdvanced NSCLC patients with EGFR activating mutation (L858R, 19Del) received Gefitinib 250mg Qd orally until progression, intolerable toxicity or death.
  • Gefitinib
Gefitinib combined with chemotherapyExperimentalGefitinib 250mg Qd combined with pemetrexed or gemcitabine plus carboplatin: Pemetrexed (500mg/m²day 1 intravenously) plus carboplatin (AUC=5,day 1,intravenously) every 21 days, Gemcitabine (1000 mg/m² days 1,d8, intravenously) plus carboplatin (AUC=5,day 1,intravenously) every 21 days
  • Gefitinib
  • pemetrexed or gemcitabine plus carboplatin,
Gefitinib combined with antiangiogenesisExperimentalGefetinib 250mg Qd combined with bevacizumab 7.5mg/kg per 21 days
  • Gefitinib
  • bevacizumab

Eligibility Criteria

        Inclusion Criteria:

          -  Histologically documented, locally advanced or recurrent (stage IIIb and not amenable
             to combined modality treatment) or metastatic (stage IV) non-small cell lung cancer,
             anti-cancer treatment naiive

          -  EGFR exon 19 deletion or exon 21 L858R.

          -  Bim deletion by realtime PCR, or low abundance for EGFR mutation, for 19Del less than
             4.9%, for L858R less than 9.5%.

          -  ECOG performance status of ≤ 1.

          -  Patients must have measurable disease according to the RECIST (version 1.1) criteria.

          -  Life expectancy of at least 12 weeks

          -  Written (signed) informed Consent to participate in the study.

          -  Adequate organ function as defined by the following criteria:

        Liver function: SGOT (AST) and SGPT (ALT) ≤ 2.5 X ULN in the absence of liver metastases or
        up to 5 X ULN in case of liver metastases. Total bilirubin ≤ 1.5ULN.

        Bone marrow function: Granulocyte count ≥ 1,500/mm3 and platelet count ≥100,000/mm3 and
        hemoglobin ≥90g/dl.

        Renal function: serum creatinine ≤ 1.5 ULN or creatinine clearance ≥ 60 ml/min. (based on
        modified Cockcroft-Gault formula).

          -  For all females of childbearing potential a negative serum/urine pregnancy test must
             be obtained within 48 hours before enrollment. Postmenopausal women must have been
             amenorrhoeic for at least 12 months to be considered of non-childbearing potential.

        Exclusion Criteria:

          -  Patients with prior chemotherapy or systemic anti-cancer therapy including target
             therapy targeting HER family members (such as erlotinib, gefitinib, cetuximab,
             trastuzumab, etc). Previous adjuvant or neo-adjuvant treatment for non-metastatic
             disease is permitted if completed ≥ 6 months before the enrollments.

          -  Patients with history of any other malignancies within 5 years (except for adequately
             treated carcinoma in situ of the cervix or basal or squamous cell skin cancer).

          -  Patients who have brain metastasis or spinal cord compression. It is permitted if the
             patient has been treated with surgery and/or radiation with evidence of stable disease
             for at least 4 weeks.

          -  Patients who are at risk (in the investigator's opinion) of transmitting human
             immunodeficiency virus (HIV) through blood or other body fluids.

          -  lactating women

          -  Sexually active males and females (of childbearing potential) unwilling to practice
             contraception during the study.

          -  Unwilling to write informed consent to participate in the study or unwilling to
             receive follow-up

          -  Tumor invade big vessels or close to big vessels (less than 5mm)

          -  Obvious cavity or necrosis formed in the tumor, Uncontrolled hypertension, Myocardial
             ischemia or infarction more than stage II, cardiac insufficiency. Abnormal coagulation
             (INR>1.5 or PT>ULN+4, or APTT>1.5 ULN), bleeding tendency or receiving coagulation
             therapy

          -  Hemoptysis, more than 2.5ml daily

          -  Thrombosis in 12 months, including pulmonary thrombosis, stoke, or deep venous
             thrombosis.

          -  Unhealed bone fracture or wound for long time
      
Maximum Eligible Age:70 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression free survival
Time Frame:8 weeks
Safety Issue:
Description:From start of anti-cancer therapy untill progression or death

Secondary Outcome Measures

Measure:overall survival
Time Frame:36 months
Safety Issue:
Description:evaluated in the 36th since treatment begain
Measure:side effect
Time Frame:8 weeks
Safety Issue:
Description:toxicities related to anti-cancer therapy
Measure:quality of life
Time Frame:24 months
Safety Issue:
Description:evaluated since treatment began

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Caicun Zhou

Trial Keywords

  • NSCLC, EGFR, Bim, mutation abundance

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