Clinical Trials /

Gefitinib With Chemotherapy or Anti-angiogenesis in NSCLC Patients With Bim Deletion or Low EGFR Mutation Abundance

NCT03267654

Description:

This is an open-label, multicenter, randomized, phase II clinical trial, which aims to evaluate the effectiveness and safety of gefitinib versus combination of gefitinib and doublet chemotherapy or apatinib in advanced non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) activating mutation (exon 19 deletion or exon 21 L858R point mutation), accompanied with Bim deletion or low activating EGFR mutation abundance.

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

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Gefitinib With Chemotherapy or Anti-angiogenesis in NSCLC Patients With Bim Deletion or Low EGFR Mutation Abundance
  • Official Title: Gefitinib Versus 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:A Randomized, Multicentre, Phase II Study

Clinical Trial IDs

  • ORG STUDY ID: SHENKANG
  • NCT ID: NCT03267654

Conditions

  • Non-small-cell Lung Cancer

Interventions

DrugSynonymsArms
gefitinib combined with chemotherapyyiruikegefitinib combined with chemotherapy
gefitinib combined with apatinibyiruikegefitinib combined with apatinib
gefitinib single agentyiruikegefitinib single agent

Purpose

This is an open-label, multicenter, randomized, phase II clinical trial, which aims to evaluate the effectiveness and safety of gefitinib versus combination of gefitinib and doublet chemotherapy or apatinib in advanced non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) activating mutation (exon 19 deletion or exon 21 L858R point mutation), accompanied with Bim deletion or low activating EGFR mutation abundance.

Detailed Description

      BIM (bcl-2 interacting mediator of cell death) deletion polymorphism and low EGFR mutation
      abundance were poor clinical response markers to epidermal growth factor receptor tyrosine
      kinase inhibitors (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
      above risk factors.

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

      A: gefitinib 250mg Qd combined with doublet chemotherapy: pemetrexed (500mg/m²,day 1
      ,intravenously) plus carboplatin (AUC=5,day 1,intravenously) every 21 days.

      B: gefitinib 250mg Qd combined with apatinib 250mg/d intravenously per 21 days. C: gefitinib
      250mg Qd
    

Trial Arms

NameTypeDescriptionInterventions
gefitinib combined with chemotherapyExperimentalgefitinib 250mg Qd combined with pemetrexed plus carboplatin: pemetrexed (500mg/m²day 1 intravenously) plus carboplatin (AUC=5,day 1,intravenously) every 21 days.
  • gefitinib combined with chemotherapy
gefitinib combined with apatinibExperimentalgefitinib 250mg Qd combined with apatinib 250mg per 21 days
  • gefitinib combined with apatinib
gefitinib single agentActive ComparatorAdvanced NSCLC patients with EGFR activating mutation (L858R, 19Del) received gefitinib 250mg Qd orally until progression, intolerable toxicity or death.
  • gefitinib single agent

Eligibility Criteria

        Inclusion Criteria:

          1. Volunteered for attending the study, and signed informed consent form (ICF)to
             participate in the study.

          2. Cytologically and Histologically documented, locally advanced or recurrent or
             metastatic (stage IIIb, IIIc, IV) non-small cell lung cancer patients .

          3. EGFR mutation (exon 19 deletion or exon 21 L858R) with Bim deletion or low abundance
             for EGFR mutation.

          4. Age range: 18 years to 75 years.

          5. Patients must have measurable lesion according to the RECIST (version 1.1) criteria.

          6. Life expectancy of ≥ 12 weeks

          7. ECOG (Eastern Cooperative Oncology Group) performance status of ≤ 1.

          8. Patients hadn't received past system treatment, including cytotoxic drugs; For
             patients who have received adjuvant or neoadjuvant chemotherapy appears recurrence or
             metastasis more than 6 months from accepting the last dose of chemotherapy drugs

          9. Adequate organ function as defined by the following criteria:

               -  Bone marrow function: absolute neutrophil count ≥ 1,500,000,000/L and platelet
                  count ≥100,000,000,000/L and hemoglobin ≥9g/dL.

               -  Liver function: Total bilirubin ≤ 1.5 ULN (upper limit of normal). AP (alkaline
                  phosphatase), AST ( aspartate aminotransferase) and ALT (alanine transaminase) ≤
                  3 ULN in the absence of liver metastases or up to 5 ULN in case of liver
                  metastases.

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

               -  INR (international normalized ratio)≤ 1.5, and partial thromboplastin time (PTT)
                  or activated partial thromboplastin time (aPTT) ≤ 1.5 ULN.

         10. 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.

         11. Fertile men and women must use effective contraception.

        Exclusion Criteria:

          1. Histology confirmed for squamous carcinomas, including mixed gland scale cancer, small
             cell lung cancer.

          2. Poor controlled hypertension, it means systolic pressure ≥140 mmHg and/or diastolic
             pressure ≥90 mmHg after drug therapy.

          3. There are imaging evidence of tumor invading or closing to the pulmonary vessels
             (e.g., pulmonary artery, superior vena cava).

          4. Thrombosis in 6 months before enrollment, including pulmonary thrombosis or deep
             venous thrombosis., or patient had medical evidence or history of thrombosis or
             bleeding tendency regardless of the severity.

          5. Patients with medical history of hemoptysis (defined as about 2.5ml bright blood) 2
             weeks before the enrollments.

          6. Proteinuria ≥++, or 24h proteinuria ≥1.0g.

          7. A uncontrolled clinical infection, activity, including but not limited to acute
             pneumonia.

          8. Patients with known liver disease: the hepatitis B virus (HBV) infection and hepatitis
             b virus DNA (HBV DNA) ≥ 500 copy number or ≥100 IU/ml; or more; or hepatitis C virus
             (HCV) infection; or liver cirrhosis, etc.

          9. Patients who are at risk of human immunodeficiency virus (HIV) or syphilis infection.

         10. Patients who have a difficulty in swallowing or drug absorption.

         11. There are diseases of alimentary canal such as active duodenal ulcer, the ulcerous
             colitis, intestinal obstruction or other conditions which can cause gastrointestinal
             bleeding or perforation in the investigator's opinion; or patient has a history of
             intestinal perforation, intestinal fistula.

         12. Evaluation of cardiac function: left ventricular ejection fraction < 50%
             (echocardiography); Moderate or above disorders of mitral valve and tricuspid shut
             down;, serious/unstable angina or acute myocardial infarction coronary artery bypass
             surgery in 6 months before enrollment; patients with class 2 and above cardiac
             dysfunction according to New York heart association (NYHA) classification

         13. Stroke and transient ischemic in 12 months before enrollment.

         14. severe ulcer in the skin wound, trauma and mucosa or fractures have been not fully
             healed.

         15. Patients received CYP3A4 strong inhibitor and/or inducer in 2 weeks before enrollment;
             Patients received P-gp and breast cancer resistance protein (BCRP) substrates drug in
             2 weeks before enrollment.

         16. Patients received other anti-tumor treatment at the same time.

         17. Patients exist serious psychological or mental abnormalities, so patient compliance is
             not sufficient.

         18. Poorly controlled serous cavity effusion, including but not limited to malignant
             pleural effusion, malignant pericardial effusion and malignant peritoneal effusion.

         19. Patients have a weight loss (≥10%) within 6 weeks before enrollment.

         20. The pregnancy of female patients test is positive or lactation women.

         21. Patients haven't been diagnosed other malignant disease, except the basal cell
             carcinoma and cervical carcinoma.
      
Maximum Eligible Age:75 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 until progression or death

Secondary Outcome Measures

Measure:overall survival
Time Frame:36 months
Safety Issue:
Description:evaluated in the 36th since treatment begain
Measure:objective response rate
Time Frame:8 weeks
Safety Issue:
Description:Evaluated the rate of complete response and partial response in the 8 weeks since treatment began
Measure:disease control rate
Time Frame:8 weeks
Safety Issue:
Description:Evaluated the rate of complete response,partial response and stable disease in the 8 weeks since anti-cancer therapy
Measure:duration of response
Time Frame:8 weeks
Safety Issue:
Description:interval between the time which complete response or partial response happened and progressive disease or death
Measure:safety evaluation
Time Frame:8 weeks
Safety Issue:
Description:Safety observation indexes were listed as following: adverse events and serious adverse events (according to CommonTerminology Criteria Adverse Events Version 4.03), physical exam, vital signs(blood pressure, heart rate, respiratory rate,body temperature), weight variation, laboratory examination(hematology, blood biochemistry, urinalysis and so on), electrocardiograph(ECG),ultrasonic cardiogram(UCG), ect.
Measure:compare quality of life
Time Frame:24 months
Safety Issue:
Description:Quality of Life Questionnaire(including QLQ-C30 and QLQ-LC13) evaluated since treatment began.At the end of the trial, the differences between the two indicators were compared with Mixed-effects model repeated measures (MMRM), where the baseline was scored as a covariant and the treatment group as a fixed variable. In addition, the baseline values of the two scores, the value of each visit, and the change value of the baseline were statistically described.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Qilu Pharmaceutical Co., Ltd.

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