Osimertinib With or Without Bevacizumab in Treating Patients With EGFR Positive Non-small Cell Lung Cancer and Brain Metastases

Running, not enrolling · Phase 2

Conditions studied: Metastatic Lung Non-Small Cell Carcinoma, Metastatic Malignant Neoplasm in the Brain, Stage IV Lung Cancer AJCC v8

In brief

This phase II trial studies how well osimertinib with or without bevacizumab works in treating patients with EGFR positive non-small cell lung cancer that has spread to the brain (brain metastases). Osimertinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Bevacizumab may stop or slow non-small cell lung cancer by blocking the growth of new blood vessels necessary for tumor growth. Giving osimertinib with or without bevacizumab may work better in treating patients with non-small cell lung cancer.

Key facts

Study ID

NCT02971501

Run by

National Cancer Institute (NCI)

People needed

5

Starts

2018-06-27

Expected to finish

2027-07-01

Last updated by the study team

2026-07-21

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Non-small cell lung cancer (NSCLC) with an activating EGFR mutation (exon 19 deletion, L858R point mutation, or any other mutation known to be associated with EGFR TKI sensitivity); presence of an activating EGFR mutation may be documented in tumor tissue or by plasma testing if performed in a Clinical Laboratory Improvement Act (CLIA)-certified laboratory
• No prior treatment with an EGFR TKI; patient may have received prior chemotherapy for early-stage or advanced disease but this is not required; prior immunotherapy is not allowed
• Patients must have at least one measurable CNS lesion that is asymptomatic, untreated, and does not require local therapy at the time of enrollment; measurable CNS disease is defined as a brain metastasis that can be accurately measured in at least one dimension (longest diameter to be recorded) as >= 5 mm (>= 0.5 cm) with brain magnetic resonance imaging (MRI); if the lesion is 5-10 mm in size and is the only measurable disease, MRI imaging must be performed with 1.5 mm slice thickness or less; a history of previously treated brain metastases is allowed, however any lesion present at the time of whole brain radiotherapy or included in the stereotactic radiotherapy field (or within 2 mm of the treated lesion) will NOT be considered "untreated" unless it is new or documented to have progressed unequivocally since treatment
• Patients are not required to have measurable systemic (i.e. non-CNS) disease; if present, measurable systemic disease must be able to be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as >= 20 mm (>= 2 cm) with conventional techniques or as >= 10 mm (>= 1 cm) with spiral computed tomography (CT) scan, MRI, or calipers by clinical exam
• Age >= 18 years
• Eastern Cooperative Oncology Group (ECOG) performance status =< 2
• Life expectancy of greater than 3 months
• The use of anti-convulsants is allowed, as long as the patient is on a stable dose with no seizure activity for at least 2 weeks prior to initiating trial therapy
• Female subjects should be using highly effective contraceptive measures, and must have a negative pregnancy test and not be breast-feeding prior to start of dosing if of child- bearing potential or must have evidence of non-child-bearing potential by fulfilling one of the following criteria at screening:
• Post-menopausal defined as aged more than 50 years and amenorrheic for at least 12 months following cessation of all exogenous hormonal treatments
• Women under 50 years old would be consider postmenopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and with luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels in the post-menopausal range for the institution
• Documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not tubal ligation
• Fertile men should be willing to use barrier contraception during and for 4 months after osimertinib (AZD9291), and fertile women must agree to use adequate contraceptive measures during and for 6 weeks after osimertinib (AZD9291); fertile men and women must agree to use adequate contraceptive measures during study therapy and for at least 6 months after the completion of bevacizumab therapy; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, the patient should inform the treating physician immediately
• Ability to understand and the willingness to sign a written informed consent document

You may not qualify if…

• Symptomatic brain metastases or symptomatic leptomeningeal disease; asymptomatic leptomeningeal disease is allowed
• Patients with brain metastases for whom complete surgical resection is clinically appropriate
• Prior treatment with any EGFR TKI
• Prior treatment with agents targeting the VEGF pathway, including bevacizumab
• The use of corticosteroids to control cerebral edema or treat neurologic symptoms will not be allowed, and patients who previously required corticosteroids for symptom control must be off steroids for at least 3 days without recurrence of symptoms prior to starting trial therapy; corticosteroids for other indications is allowed
• Patients may not be receiving any other investigational agents and may not have participated in a study of an investigational agent or using an investigational device within five half-lives of the compound or 3 months, whichever is greater
• Any unresolved toxicities from prior therapy greater than Common Terminology Criteria for Adverse Events (CTCAE) grade 1 at the time of starting study treatment with the exception of alopecia and grade 2 platinum-therapy related neuropathy
• Concurrent, active malignancies in addition to that being studied (other than cutaneous squamous cell carcinoma or basal cell carcinoma)
• Any contraindication to MRI (i.e. patients with pacemakers or other metal implanted medical devices)
• Past medical history of interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonitis which required steroid treatment, or any evidence of clinically active interstitial lung disease
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to osimertinib (AZD9291) or bevacizumab
• Urine protein should be screened by urine analysis; if protein is 2+ or higher, 24-hour urine protein should be obtained; patients with 24-hour urine protein >= 1000 mg are excluded
• Serious or non-healing wound, ulcer or bone fracture
• History of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess within 6 months prior to day 1
• Invasive procedures defined as follows:
• Major surgical procedure, open biopsy or significant traumatic injury within 28 days prior to day 1 therapy
• Anticipation of need for major surgical procedures during the course of the study
• Core biopsy within 7 days prior to day 1 (D1) therapy
• Significant vascular disease (e.g., aortic aneurysm, requiring surgical repair or recent peripheral arterial thrombosis) within 6 months prior to day 1
• Patients with clinically significant cardiovascular disease are excluded
• Inadequately controlled hypertension (HTN) (systolic blood pressure [SBP] > 160 mmHg and/or diastolic blood pressure [DBP] > 90 mmHg despite antihypertensive medication)
• History of cerebrovascular accident (CVA) within 6 months (see additional requirement for adjuvant protocols)
• Myocardial infarction or unstable angina within 6 months (see additional requirement for adjuvant protocols)
• New York Heart Association grade II or greater congestive heart failure
• Serious and inadequately controlled cardiac arrhythmia

Where it is running

• Los Angeles General Medical Center — Los Angeles, California, United States
• USC / Norris Comprehensive Cancer Center — Los Angeles, California, United States
• Keck Medical Center of USC Pasadena — Pasadena, California, United States
• University of California Davis Comprehensive Cancer Center — Sacramento, California, United States
• Smilow Cancer Center/Yale-New Haven Hospital — New Haven, Connecticut, United States
• Yale University — New Haven, Connecticut, United States
• Moffitt Cancer Center-International Plaza — Tampa, Florida, United States
• Moffitt Cancer Center — Tampa, Florida, United States
• University of Kansas Clinical Research Center — Fairway, Kansas, United States
• University of Kansas Hospital-Westwood Cancer Center — Westwood, Kansas, United States
• Nebraska Medicine-Bellevue — Bellevue, Nebraska, United States
• Nebraska Medicine-Village Pointe — Omaha, Nebraska, United States
• University of Nebraska Medical Center — Omaha, Nebraska, United States
• NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center — New York, New York, United States
• Ohio State University Comprehensive Cancer Center — Columbus, Ohio, United States
• University of Oklahoma Health Sciences Center — Oklahoma City, Oklahoma, United States
• University of Pittsburgh Cancer Institute (UPCI) — Pittsburgh, Pennsylvania, United States
• Huntsman Cancer Institute/University of Utah — Salt Lake City, Utah, United States

Full record on ClinicalTrials.gov

Trial information comes from ClinicalTrials.gov and is refreshed daily. TrialsForMe does not provide medical care and does not run the studies it lists.