New drug combo shows promise for lung cancer brain metastases
NCT ID NCT02971501
First seen Jun 27, 2026 · Last updated Aug 14, 2026 · Updated 5 times
Summary
This phase II trial tested whether adding bevacizumab to osimertinib works better than osimertinib alone for patients with a specific type of lung cancer (EGFR-mutant non-small cell lung cancer) that has spread to the brain. Only 5 patients were enrolled. The goal was to see if the combination could delay cancer progression and improve survival.
What this could mean
Our plain-language read of the trial. This is informational only, not medical advice or a prediction.
- Active substance
- osimertinib and bevacizumab
- What this could lead to
- If successful, this could point toward a more effective treatment for lung cancer that has spread to the brain, potentially improving how long patients live without the disease getting worse.
- What could go wrong
- This is a very small, early-phase trial with only 5 participants, so results may not apply to all patients. The study was terminated early, making it hard to draw firm conclusions.
This is an AI summary of the original study and may miss details. Read our disclaimer.
Study facts
What this study's own registry entry says, in plain language.
- Phase
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Phase 2
Tests whether the treatment actually works, and watches for side effects, in a larger group.
- Participants
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5 people
The number who actually took part.
- Started
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Jun 2018
- Expected to finish
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Jul 2027
An estimate. End dates often move.
- Lead sponsor
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A government research agency
The lead sponsor is the US National Institutes of Health.
Who can take part
This study's own entry requirements. Only the study team can say for certain whether you qualify.
- Ages
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18 years and older
- Sex
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Anyone
- Healthy volunteers
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Not accepted
This study is not open to healthy volunteers. The entry requirements below say who it is open to.
Show the full entry requirements Hide the full entry requirements
Copied word for word from the study's registry entry, so the wording is the study team's rather than ours.
Inclusion Criteria: * 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 Exclusion Criteria: * 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 * Significant vascular disease (e.g. aortic aneurysm, history of aortic dissection) * Clinically significant peripheral vascular disease * Any of the following cardiac criteria: * Mean resting corrected QT interval (Fridericia's correction formula \[QTcF\]) \> 470 ms obtained from 3 electrocardiograms (ECGs), using the screening clinic ECG machine derived corrected QT (QTc) value * Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG (e.g., complete left bundle branch block, third degree heart block, second degree heart block) * Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalemia, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age in first degree relatives or any concomitant medication known to prolong the QT interval * Evidence of bleeding diathesis or coagulopathy (including clinically significant hemoptysis) * Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product or previous significant bowel resection that would preclude adequate absorption of osimertinib (AZD9291) * Patients with known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies * Patients currently receiving (or unable to stop use prior to receiving the first dose of study treatment) medications or herbal supplements known to be potent inducers of CYP3A4 (at least 3 weeks prior); all patients must try to avoid concomitant use of any medications, herbal supplements and/or ingestion of foods with known inducer effects on CYP3A4 * Any evidence of severe or uncontrolled systemic diseases, including, but not limited to, uncontrolled hypertension, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations which in the investigator's opinion makes it undesirable for the patient to participate in the trial or which would jeopardize compliance with the protocol, or active infection including hepatitis B, hepatitis C and human immunodeficiency virus (HIV); screening for chronic conditions is not required * History of hypersensitivity active or inactive excipients of osimertinib (AZD9291) or drugs with a similar chemical structure or class to osimertinib (AZD9291) * Absolute neutrophil count \< 1.5 x 10\^9/L * Platelet count \< 100 x 10\^9/L * Hemoglobin \< 90 g/L * Alanine aminotransferase \> 2.5 times upper limit of normal (ULN) if no demonstrable liver metastases or \> 5 times ULN in the presence of liver metastases; aspartate aminotransferase \> 2.5 times ULN if no demonstrable liver metastases or \> 5 times ULN in the presence of liver metastases * Total bilirubin \> 1.5 times ULN if no liver metastases or \> 3 times ULN in the presence of documented Gilbert's syndrome (unconjugated hyperbilirubinemia) or liver metastases * Serum creatinine \> 1.5 times ULN concurrent with creatinine clearance \< 50 mL/min (measured or calculated by Cockcroft and Gault equation)-confirmation of creatinine clearance is only required when creatinine is \> 1.5 times ULN * Judgment by the investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions and requirements
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Conditions
The condition(s) this trial relates to.
As listed by the trial registrant
The condition terms exactly as the trial's registrant entered them.
Contacts and locations
Locations
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Huntsman Cancer Institute/University of Utah
Salt Lake City, Utah, 84112, United States
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Keck Medical Center of USC Pasadena
Pasadena, California, 91105, United States
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Los Angeles General Medical Center
Los Angeles, California, 90033, United States
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Moffitt Cancer Center
Tampa, Florida, 33612, United States
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Moffitt Cancer Center-International Plaza
Tampa, Florida, 33607, United States
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NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
New York, New York, 10032, United States
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Nebraska Medicine-Bellevue
Bellevue, Nebraska, 68123, United States
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Nebraska Medicine-Village Pointe
Omaha, Nebraska, 68118, United States
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Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43210, United States
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Smilow Cancer Center/Yale-New Haven Hospital
New Haven, Connecticut, 06510, United States
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UPMC Hillman Cancer Center
Pittsburgh, Pennsylvania, 15232, United States
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USC / Norris Comprehensive Cancer Center
Los Angeles, California, 90033, United States
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University of California Davis Comprehensive Cancer Center
Sacramento, California, 95817, United States
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University of Kansas Clinical Research Center
Fairway, Kansas, 66205, United States
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University of Kansas Hospital-Westwood Cancer Center
Westwood, Kansas, 66205, United States
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University of Nebraska Medical Center
Omaha, Nebraska, 68198, United States
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University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, 73104, United States
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Yale University
New Haven, Connecticut, 06520, United States
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