Clinical Trials /

Study Comparing Bevacizumab + Erlotinib vs Erlotinib Alone as First Line Treatment of Patients With EGFR Mutated Advanced Non Squamous Non Small Cell Lung Cancer

NCT02633189

Description:

The purpose of this study is to test whether the combination of bevacizumab and erlotinib can prolong progression free survival as compared with erlotinib alone as first-line treatment in patients with non small cell lung cancer (NSCLC) with activating mutation of EGFR.

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

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: Study Comparing Bevacizumab + Erlotinib vs Erlotinib Alone as First Line Treatment of Patients With EGFR Mutated Advanced Non Squamous Non Small Cell Lung Cancer
  • Official Title: A Randomized Open-label Phase 3 Trial Comparing Bevacizumab + Erlotinib vs Erlotinib Alone as First Line Treatment of Patients With EGFR Mutated Advanced Non Squamous Non Small Cell Lung Cancer

Clinical Trial IDs

  • ORG STUDY ID: BEVERLY
  • SECONDARY ID: 2015-002235-17
  • NCT ID: NCT02633189

Conditions

  • Non-squamous Non-small Cell Lung Cancer

Interventions

DrugSynonymsArms
Erlotiniberlotinib and bevacizumab
Bevacizumaberlotinib and bevacizumab

Purpose

The purpose of this study is to test whether the combination of bevacizumab and erlotinib can prolong progression free survival as compared with erlotinib alone as first-line treatment in patients with non small cell lung cancer (NSCLC) with activating mutation of EGFR.

Detailed Description

      The co-primary objectives are to assess investigator-assess, and blinded independent
      centrally-reviewed progression-free survival .
    

Trial Arms

NameTypeDescriptionInterventions
erlotinib and bevacizumabExperimental
  • Erlotinib
  • Bevacizumab
erlotinibActive Comparator
  • Erlotinib

Eligibility Criteria

        Inclusion Criteria:

          1. Age ≥18 years

          2. Histological documentation of primary non squamous lung carcinoma

          3. Stage IV or IIIB disease with supraclavicular metastatic nodes (according to TNM 7th
             edition)

          4. Activating epidermal growth factor receptor mutation (exon19 deletion or exon 21 L858R
             mutation or other activating/sensitizing mutations, such as exon 21 L861Q, exon 18
             G719S, G719A and G719C, exon 20 S768I and V769L). EGFR mutation testing must be
             performed at participating centres in a certified lab (AIOM-SIAPEC program or other
             European Quality Assurance [EQA] schemes)

          5. Clinical or radiologic evidence of disease (at least one target or non target lesion
             according to RECIST 1.1)

          6. ECOG performance status 0 to 2

          7. Life expectancy > 3 months

          8. Use of an acceptable mean of contraception for men and women of childbearing potential

          9. Written informed consent.

        Exclusion Criteria:

          1. EGFR T790M mutation alone or exon 20 insertions as unique mutation

          2. Tumors with a squamous component

          3. Prior chemotherapy or any other medical treatment for advanced NSCLC (previous
             neoadjuvant or adjuvant chemotherapy is allowed if > 6 months before randomisation)

          4. Radiotherapy to any site for any reason within 28 days prior to randomization
             (palliative radiotherapy to bone lesions is allowed if ≥ 14 days before randomization)

          5. Full-dose anticoagulation with warfarin

          6. Current or recent (within 10 days of enrolment) use of aspirin (>325 mg/day) or
             chronic use of other full-dose nonsteroidal anti-inflammatory drugs (NSAIDs) with
             anti-platelet activity

          7. Receiving any medications or substances that are strong or moderate inhibitors of
             cytochrome P450 3A4 (CYP3A4) are prohibited =< 7 days prior to registration

          8. Receiving any medications or substances that are inducers of CYP3A4 use of inducers
             are prohibited =< 7 days prior to registration

          9. Inadequate coagulation parameters:

               -  activated partial thromboplastin time (APTT) >1.5 x the upper limit of normal
                  (ULN) or

               -  INR >1.5

         10. Inadequate liver function, defined as:

               -  serum (total) bilirubin >1.5 x ULN

               -  AST/SGOT or ALT/SGPT >2.5 x ULN

         11. Inadequate renal function, defined as:

               -  serum creatinine >2.0 mg/dl or >177 micromol/l

               -  urine dipstick for proteinuria >2+. Patients with > o = 1+ proteinuria at
                  baseline dipstick analysis must undergo a 24-hour urine collection and must
                  demonstrate ≤1g of protein in their 24-hour urine collection.

         12. Pregnancy or breast-feeding

         13. Inadequately controlled hypertension (defined as systolic blood pressure >150 and/or
             diastolic blood pressure >100 mmHg on antihypertensive medications)

         14. History of gross hemoptysis within 3 months prior to randomization unless definitively
             treated with surgery or radiation

         15. History of any of the following within 6 months prior to randomisation: serious
             systemic disease, unstable angina, New York Heart Association (NYHA) Grade 2 or
             greater Congestive Heart Failure (CHF), unstable symptomatic arrhythmia requiring
             medication, clinically significant peripheral vascular disease, abdominal fistula,
             gastrointestinal perforation, or intra-abdominal abscess

         16. Serious, non-healing wound, ulcer, or bone fracture

         17. Evidence of bleeding diathesis or coagulopathy or other serious or acute internal
             bleeding within 6 months prior to randomization

         18. Central Nervous System (CNS) bleeding; history or clinical evidence of CNS stroke
             (hemorrhagic or thrombotic) within the last 6 months

         19. In-patient surgical procedure, open biopsy, or significant traumatic injury within 28
             days prior to randomization

         20. Minor surgical procedure, fine needle aspirations or core biopsy within 7 days prior
             to randomization

         21. Anticipation of need for a major surgical procedure during the course of the study

         22. Inability to take oral medication or requirement for intravenous (IV) alimentation or
             total parenteral nutrition with lipids, or prior surgical procedures affecting
             absorption

         23. Evidence of confusion or disorientation, or history of major psychiatric illness that
             may impair the patient's understanding of the Informed Consent Form or his/her ability
             to comply with study requirements

         24. Any other invasive malignancies within 5 years (except for adequately treated
             carcinoma in situ of the cervix or basal or squamous cell skin cancer or surgically
             resected prostate cancer with normal PSA)

         25. Brain metastasis

         26. Patients who have had radiotherapy ≥ 4 weeks prior to the first dose of study
             treatment, but who are still experiencing acute toxic effects of radiotherapy

         27. Known HIV positive patients (patients with both acute or chronic infection are
             excluded)

         28. Active HBV or HCV infection (patients with chronic non-active infection are eligible)

         29. Any already known inflammatory changes of the surface of the eye at baseline

         30. Any other concomitant pathologies or laboratory alterations that prevent or
             contraindicate the use of erlotinib or bevacizumab.
      
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:up to 2 years
Safety Issue:
Description:as determined by investigator

Secondary Outcome Measures

Measure:overall survival
Time Frame:1 year
Safety Issue:
Description:
Measure:changes in quality of life scores from baseline
Time Frame:up to 2 years
Safety Issue:
Description:
Measure:number of patients with complete and partial responses , investigator assessed
Time Frame:6 months
Safety Issue:
Description:
Measure:number of patients with complete and partial responses , centrally reviewed
Time Frame:6 months
Safety Issue:
Description:
Measure:worst grade toxicity per patient
Time Frame:up to one year
Safety Issue:
Description:
Measure:progression free survival according to type of EGFR mutation (exon 19del, exon 21L858R, other)
Time Frame:2 years
Safety Issue:
Description:

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:National Cancer Institute, Naples

Trial Keywords

  • stage IV
  • stage IIIB
  • EGFR mutation
  • non-squamous
  • liquid biopsy
  • erlotinib
  • bevacizumab

Last Updated