Clinical Trials /

Osimertinib and Bevacizumab as Treatment for EGFR-mutant Lung Cancers

NCT02803203

Description:

The purpose of this study is to test the safety of combining the drugs osimertinib and bevacizumab at different dose levels. The investigators want to find out what effects, good and/or bad, taking osimertinib and bevacizumab has on the patient and lung cancer. This study will try to find the best dose of osimertinib and bevacizumab given together that does not cause significant side effects. Once the investigators determine that combining osimertinib and bevacizumab is safe, they want to see if the combination is effective in treating lung cancers with the EGFR mutation.

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

Active, not recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

<span class="go-doc-concept go-doc-intervention">Osimertinib</span> and <span class="go-doc-concept go-doc-intervention">Bevacizumab</span> as Treatment for <span class="go-doc-concept go-doc-biomarker">EGFR</span>-<span class="go-doc-concept go-doc-keyword">mutant</span> Lung Cancers

Title

  • Brief Title: Osimertinib and Bevacizumab as Treatment for EGFR-mutant Lung Cancers
  • Official Title: A Phase 1/2 Study of Combination Osimertinib and Bevacizumab as Treatment for Patients With EGFR-mutant Lung Cancers
  • Clinical Trial IDs

    NCT ID: NCT02803203

    ORG ID: 16-033

    Trial Conditions

    Non-small Cell Lung Cancer

    EGFR-mutant Lung Cancers

    Trial Interventions

    Drug Synonyms Arms
    osimertinib AZD9291 osimertinib and bevacizumab
    Bevacizumab osimertinib and bevacizumab

    Trial Purpose

    The purpose of this study is to test the safety of combining the drugs osimertinib and
    bevacizumab at different dose levels. The investigators want to find out what effects, good
    and/or bad, taking osimertinib and bevacizumab has on the patient and lung cancer. This
    study will try to find the best dose of osimertinib and bevacizumab given together that does
    not cause significant side effects. Once the investigators determine that combining
    osimertinib and bevacizumab is safe, they want to see if the combination is effective in
    treating lung cancers with the EGFR mutation.

    Detailed Description

    Trial Arms

    Name Type Description Interventions
    osimertinib and bevacizumab Experimental Phase 1: 3+3 dose escalation design 2 dose levels Dose level -1: Osimertinib 60mg daily Maximum accrual = 12 Bevacizumab 15mg/kg q3 weeks Dose level 1: Osimertinib 80mg daily Bevacizumab 15mg/kg q3 Weeks Phase 2: Use MTD determined during phase 1 osimertinib, Bevacizumab

    Eligibility Criteria

    Inclusion Criteria:

    - Written informed consent

    - Advanced biopsy-proven metastatic non-small cell lung cancer

    - Somatic activating mutation in EGFR

    - No prior treatment with an EGFR TKI

    - No prior treatment with a VEGF inhibitor

    - Measurable (RECIST 1.1) indicator lesion not previously irradiated

    - Karnofsky performance status (KPS) 70%

    - Age >18 years old

    - Adequate organ function

    - AST, ALT 3 x ULN

    - Total bilirubin 1.5x ULN

    - Creatinine 1.5x ULN OR calculated creatinine clearance > 60ml/min

    - Absolute neutrophil count (ANC) 1000 cells/mm3

    - Hemoglobin8.0 g/dL

    - Platelets 100,000/mm3

    Exclusion Criteria:

    - Any contra-indications to bevacizumab which include but are not limited to recent

    1. Any previous venous thromboembolism > NCI CTCAE Grade 3

    2. Severe uncontrolled hypertension (systolic blood pressure 150 mmHg and/or
    diastolic blood pressure 100mmHg)

    3. Cardiovascular disease including stroke of myocardial infarction <6 months prior
    to study enrollment, New York Heart Association Grade 2 or greater congestive
    heart failure, serious cardiac arrythmia uncontrolled by medication

    4. Hemorrhagic brain metastases. Asymptomatic (not requiring escalating doses of
    steroids) brain metastases are acceptable.

    5. Severe proteinuria (>2gm/24hrs or a urine protein to creatinine ratio 1.0)

    6. Prior history of hypertensive crisis or hypertensive encephalopathy

    7. History of a central nervous system disease (e.g. seizures) unrelated to cancer
    unless adequately treated with standard medical therapy

    8. Significant vascular disease (e.g. aortic aneurysm requiring surgical repair) 6
    months prior to study enrollment

    9. History of hemoptysis (1/2 teaspoon of bright red blood per episode) within the
    last 3 months

    10. Evidence of a bleeding diathesis or significant coagulopathy (in the absence of
    therapeutic anticoagulation)

    11. Current or recent (within 10 days of study drug start) use of aspirin (>325mg
    daily), clopidogrel (>75mg daily).

    12. Recent initiation of full dose oral or parental anticoagulants that have not
    been in place for at least 2 weeks.

    13. Tumor invading or abutting major blood vessels

    14. Tumor histology classified by squamous cell histology.

    15. Any history of abdominal fistula or GI perforation within 6 months of study
    enrollment

    - Pregnant or lactating women

    - Any type of systemic anticancer therapy (chemotherapy or experimental drugs) within 2
    weeks of starting treatment on protocol

    - Any radiotherapy within 1 week of starting treatment on protocol

    - Any major surgery within 4 weeks of starting treatment on protocol

    - Any evidence of clinically significant interstitial lung disease

    - Known hypersensitivity to any component of bevacizumab and osimertinib

    Minimum Eligible Age: 19 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    maximum tolerated dose (MTD) (Phase I)

    progression-free survival (Phase II)

    Secondary Outcome Measures

    Trial Keywords

    Osimertinib

    bevacizumab

    metastatic

    16-033