Clinical Trials /

Atezolizumab and Bevacizumab in Epidermal Growth Factor Receptor (EGFR) Mutant Non‐Small Cell Lung Cancer in Patients With Progressive Disease After Receiving Osimertinib

NCT04099836

Description:

The purpose of this study is to investigate the safety and efficacy of giving atezolizumab combined with bevacizumab in patients with stage 4 epidermal growth factor receptor (EGFR) mutant non‐small cell lung cancer (NSCLC) whose cancer has gotten worse while receiving osimertinib.

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

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Atezolizumab and Bevacizumab in Epidermal Growth Factor Receptor (EGFR) Mutant Non‐Small Cell Lung Cancer in Patients With Progressive Disease After Receiving Osimertinib
  • Official Title: Single Arm Phase 2 Trial of Atezolizumab and Bevacizumab in Epidermal Growth Factor Receptor (EGFR) Mutant Non‐Small Cell Lung Cancer in Patients With Progressive Disease After Receiving Osimertinib (TOP 1901)

Clinical Trial IDs

  • ORG STUDY ID: Pro00103723
  • NCT ID: NCT04099836

Conditions

  • Non Small Cell Lung Cancer

Interventions

DrugSynonymsArms
Atezolizumabatezolizumab and bevacizumab
Bevacizumabatezolizumab and bevacizumab

Purpose

The purpose of this study is to investigate the safety and efficacy of giving atezolizumab combined with bevacizumab in patients with stage 4 epidermal growth factor receptor (EGFR) mutant non‐small cell lung cancer (NSCLC) whose cancer has gotten worse while receiving osimertinib.

Detailed Description

      This study will be single arm, open label, phase 2 study which will include patients with
      stage 4 NSCLC patients with EGFR mutations and who have progressed on osimertinib.

      Although both atezolizumab and bevacizumab are approved for the treatment of NSCLC, the
      combination of atezolizumab and bevacizumab has not been approved by the FDA for the
      treatment of specific non-small cell lung cancer (NSCLC).

      Patients who have one of the following EGRF mutations: exon 19 or exon 21 L858R with
      progressive disease on osimertinib may be eligible to participate in this study. If enrolled
      into the study, the study team will give the patient atezolizumab (1200 mg) combined with
      bevacizumab (15 mg/kg) every 3 weeks intravenously. As part of this study, the patient will
      have blood samples, other tests, exams, and procedures done for study purposes and their
      standard of care. Patient participation in the study will last for up to 2 years after
      completion of the last dose of the study drug or until your condition worsens or intolerable
      adverse events as deemed by the study doctor.

      There are possible patient risks to this study that include but are not limited to diarrhea,
      itching, rash, and a feeling of weakness.
    

Trial Arms

NameTypeDescriptionInterventions
atezolizumab and bevacizumabExperimentalAtezolizumab 1200 mg IV every 3 weeks and bevacizumab 15 mg/kg IV every 3 weeks (1 cycle=3 weeks)
  • Atezolizumab
  • Bevacizumab

Eligibility Criteria

        Inclusion Criteria:

          1. Age ≥18 years

          2. Histologic documentation of primary lung carcinoma, non‐squamous histology with EGFR
             exon deletion 19 or exon 21 L858R mutation

          3. Stage IV disease according to the 8th Edition of the American Joint Committee on
             Cancer staging system

          4. Disease progression on osimertinib

          5. Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1 (appendix 1)

          6. Measureable disease as defined by RECIST 1.1 (appendix 2)

          7. The following laboratory values obtained ≤ 30 days prior to starting study therapy

               1. ANC ≥ 1, 500 / mm3

               2. Platelet count, ≥ 100,000 / mm3

               3. Hemoglobin ≥ 9.0 g / dL

               4. Total bilirubin ≤ 1.5 x upper limit of normal (ULN)

               5. Serum Glutamic Oxaloacetic Transaminase (SGOT) (Aspartate Aminotransferase, AST)
                  and Serum Glutamic Pyruvic Transaminase (SGPT) (Alanine Aminotransferase, ALT)
                  ≤2.5 x ULN in patients without liver or bone metastases; < 5 x ULN in patients
                  with liver or bone metastases.

               6. Cockcroft‐Gault calculated creatinine clearance of ≥ 45 ml/min (appendix 3) or
                  creatinine ≤1.5 x ULN

               7. Urine protein/creatinine (UPC) ratio ≤1.

          8. Negative pregnancy test done ≤7 days (or per institutional policy) prior to start of
             study therapy, for women of childbearing potential only. Female subjects should be
             using highly effective contraceptive measures, and must have a negative pregnancy test
             of must have evidence of non‐child bearing potential by fulfilling one of the
             following criteria at screening:

               1. Post‐menopausal defined as aged more than 50 years and amenorrheic for at least
                  12 months following cessation of all exogenous hormonal treatments;

               2. Women under 50 years of age would be considered post‐menopausal if they have been
                  amenorrheic for 12 months or more following cessation of exogenous hormonal
                  treatments and Luteinizing hormone (LH) and follicle-stimulating hormone (FSH)
                  levels in the post‐menopausal range for the institution;

               3. Documentation of irreversible surgical sterilization by hysterectomy, bilateral
                  oophorectomy or bilateral salpingectomy but not tubal ligation.

          9. Male subjects should be willing to use barrier contraception.

         10. Provide informed written consent

        Exclusion Criteria:

          1. Mixed, non‐small cell and small cell tumors or mixed adenosquamous carcinomas with a
             predominant squamous component.

          2. Any of the following because this study involves an investigational agent whose
             genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are
             unknown: pregnant women, nursing women, men or women of childbearing potential who are
             unwilling to employ adequate contraception

          3. Other active malignancy ≤ 2 years prior to study cycle 1 day 1 of study therapy.
             EXCEPTIONS: Nonmelanotic skin cancer or carcinoma‐in‐situ of the cervix, or adequately
             treated stage I or II cancer. NOTE: If there is a history of prior malignancy, they
             must not be receiving other specific treatment (i.e. hormonal therapy) for their
             cancer.

          4. History of myocardial infarction or other evidence of arterial thrombotic disease
             (angina), symptomatic congestive heart failure (New York Heart Association ≥ grade 2),
             unstable angina pectoris, or ventricular arrhythmia with ≤ 6 months

          5. History of cerebral vascular accident (CVA) or transient ischemic attack (TIA) ≤ 6
             months prior to study cycle 1 day 1 of study therapy.

          6. History of bleeding diathesis or coagulopathy.

          7. Inadequately controlled hypertension (systolic blood pressure of >160 mmHg or
             diastolic pressure >100 mmHg on anti‐hypertensive medications). Note: History of
             hypertensive crisis or hypertensive encephalopathy not allowed.

          8. Serious non‐healing wound, ulcer, bone fracture, or have undergone a major surgical
             procedure, open biopsy, or significant traumatic injury ≤ 28 days or core biopsy ≤ 7
             days prior to starting therapy

          9. History of abdominal fistula, gastrointestinal perforation, or intraabdominal abscess
             ≤6 months prior to study cycle 1 day 1 of study therapy.

         10. Known hypersensitivity to Chinese hamster ovary cell products or other recombinant
             human antibodies.

         11. History of hemoptysis ≥ grade 2 (defined as bright red blood of at least 2.5 mL) ≤ 3
             months prior to cycle 1 day 1 of study therapy.

         12. Symptomatic untreated brain metastases which is defined as persistent neurological
             symptoms or requiring ongoing use of steroids. Asymptomatic untreated brain metastases
             are allowed if ≤ 1 cm

         13. Significant vascular disease (e.g. aortic aneurysm surgical repair or recent
             peripheral arterial thrombosis) ≤6 months prior to starting study therapy

         14. Radiotherapy to any site for any reason ≤ 14 days prior to study cycle 1 day 1 of
             study therapy.

         15. Pre‐existing and clinically active interstitial lung disease

         16. Autoimmune condition requiring ongoing or intermittent systemic treatment.
             Participants with a condition requiring systemic treatment with either corticosteroids
             (>10 mg daily prednisone equivalent) or other immunosuppressive medications within 14
             days of study treatment initiation. Inhaled or topical steroids, and adrenal
             replacement steroid > 10 mg daily prednisone equivalent, are permitted in the absence
             of active autoimmune disease.

             Participants with type I diabetes mellitus, hypothyroidism only requiring hormone
             replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring
             systemic treatment, or conditions not expected to recur in the absence of an external
             trigger are permitted to enroll.

         17. Prior therapy with anti‐PD‐1 or anti‐PD‐L1 immunotherapy,

         18. Prisoners, participants who are involuntarily incarcerated, or participants who are
             compulsorily detained for treatment of either a psychiatric or physical (e.g.,
             infectious disease) illness
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Objective response rate (ORR) as assessed by the investigator using Response Evaluation Criteria in Solid Tumors RECIST 1.1 (brand name)
Time Frame:Up to 3 years
Safety Issue:
Description:RECIST 1.1 will be used to measure confirmed partial or complete responses to the study drug.

Secondary Outcome Measures

Measure:Progression free survival as measured by Response Evaluation Criteria In Solid Tumors RECIST 1.1 (brand name) as assessed by the investigator.
Time Frame:Up to 5 years
Safety Issue:
Description:Progression will be defined as time from start of study therapy to disease progression or death
Measure:Overall survival as noted by follow-up via composite of telephone or medical record review.
Time Frame:Up to 3 years
Safety Issue:
Description:Overall survival (OS) is defined as the time from start of study therapy to death from any cause, and patients who are alive at the time of analysis will be censored at the last date of contact.
Measure:AEs as measured by Common Terminology Criteria for Adverse Events (CTCAE) version 4.03
Time Frame:Up to 5 years]
Safety Issue:
Description:Evaluation of safety using the National Cancer Institute (NCI) CTCAE version 4.03

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Duke University

Trial Keywords

  • EGFR Mutation
  • Atezolizumab
  • Bevacizumab
  • exon L858R
  • exon 21 L858R

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