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[Information provided by:
ClinicalTrials.gov, which provides patients, family members, and members of the public easy and free access to information on clinical studies for a wide range of diseases and conditions.]
NCT02971501 : Osimertinib With or Without Bevacizumab in Treating Patients With EGFR Positive Non-small Cell Lung Cancer and Brain Metastases |
Phase | Phase 2 |
Ages | Min: 18 Years Max: N/A |
Eligibility | 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; AND
- The presence of an EGFR T790M mutation after progression on a first- or second-generation EGFR TKI; presence of an EGFR T790M mutation may be documented from biopsy material from any site of disease (intra- or extra-cranial) or from plasma testing if performed in a CLIA-certified laboratory; for patients who have disease progression in the CNS only (with otherwise stable disease systemically), T790M positivity is not required
- Disease progression on a first- or second-generation EGFR TKI (i.e. erlotinib, gefitinib, or afatinib); patient may have also received prior chemotherapy or immunotherapy but this is not required
- 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 MRI; if the lesion is 5-10 mm in size and is the only measurable disease, magnetic resonance imaging (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
- Eastern Cooperative Oncology Group (ECOG) performance status =< 2
- Life expectancy of greater than 3 months
- Absolute neutrophil count >= 1,500/mcL
- Platelets >= 75,000/mcL
- Total bilirubin =< 1.5 x institutional upper limit of normal if no demonstrable liver metastases or =< 3 x institutional upper limit of normal in the presence of liver metastases or Gilbert's syndrome (unconjugated hyperbilirubinemia)
- Aspartate aminotransferases (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional upper limit of normal if no demonstrable liver metastases or =< 5 x institutional upper limit of normal in the presence of liver metastases
- Creatinine within normal institutional limits OR creatinine clearance >= 50 mL/min for patients with creatinine levels above institutional normal
- The use of anti-convulsants in 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
- Fertile men must agree to use adequate contraceptive measures during and for 4 months after AZD9291 (osimertinib), and fertile women must agree to use adequate contraceptive measures during and for 6 weeks after AZD9291 (osimertinib); 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
- Patients with brain metastases for whom complete surgical resection is clinically appropriate
- Prior treatment with a third-generation EGFR TKI (i.e. rociletinib)
- 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
- Presence of leptomeningeal disease
- 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 2 weeks of the first dose of treatment
- Treatment with an EGFR TKI (i.e. erlotinib, gefitinib or afatinib) within 8 days or approximately 5 x half-life, whichever is longer, of the first dose of study treatment
- 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)
- History of clinically significant interstitial lung disease (ILD) (including drug-induced ILD), radiation pneumonitis requiring steroid treatment, or any evidence of clinically active ILD
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to osimertinib 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 using Fridericia's formula
- Any clinically important abnormalities in rhythm, conduction or morphology of resting electrocardiography (ECG) (e.g., complete left bundle branch block, third degree heart block, second degree heart block)
- Any factors that increase the risk of corrected QT (QTc) prolongation or risk of arrhythmic events
- Evidence of bleeding diathesis or coagulopathy (including clinically significant hemoptysis)
- 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 inhibitors of CYP3A4 (at least 1 week prior) and potent inducers of CYP3A4 (at least 3 week prior)
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
- Human immunodeficiency virus (HIV)-positive patients on antiretroviral therapy that is a strong inducer CYP3A4; HIV-positive patient not on strong inducers of CYP3A4 are allowed |
Links | Permanent Link to THIS page: http://virtualtrials.com/nct/display1trial.cfm?nct=NCT02971501
| Link to official Clinicaltrials.gov listing
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Locations |
Los Angeles,
California
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Facility: Los Angeles County-USC Medical Center
Investigator:
Jorge J. Nieva
Contact:
Jorge J. Nieva Phone: 323-865-0451
Email not avaialable
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Los Angeles,
California
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Facility: USC / Norris Comprehensive Cancer Center
Investigator:
Jorge J. Nieva
Contact:
Jorge J. Nieva Phone: 323-865-0451
Email not avaialable
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Pasadena,
California
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Facility: Keck Medical Center of USC Pasadena
Investigator:
Jorge J. Nieva
Contact:
Jorge J. Nieva Phone: 323-865-0451
Email not avaialable
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Sacramento,
California
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Facility: University of California Davis Comprehensive Cancer Center
Investigator:
Jonathan W. Riess
Contact:
Jonathan W. Riess Phone: 916-734-3089
Email not avaialable
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New Haven,
Connecticut
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Facility: Smilow Cancer Center/Yale-New Haven Hospital
Investigator:
Sarah B. Goldberg
Contact:
Sarah B. Goldberg Phone: 855-476-4569
Email not avaialable
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New Haven,
Connecticut
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Facility: Yale University
Investigator:
Sarah B. Goldberg
Contact:
Sarah B. Goldberg Phone: 203-785-5702
Email not avaialable
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Tampa,
Florida
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Facility: Moffitt Cancer Center
Investigator:
Peter A. Forsyth
Contact:
Peter A. Forsyth Phone: 800-456-7121
Click HERE to send email to this center
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Pittsburgh,
Pennsylvania
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Facility: University of Pittsburgh Cancer Institute (UPCI)
Investigator:
Liza C. Villaruz
Contact:
Liza C. Villaruz Phone: 412-647-8073
Email not avaialable
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