Clinical Trial Details

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

Locations

Los Angeles, California

Facility: Los Angeles County-USC Medical Center
Investigator: Jorge J. Nieva
Contact: Jorge J. Nieva Phone: 323-865-0451
Email not avaialable

Los Angeles, California

Facility: USC / Norris Comprehensive Cancer Center
Investigator: Jorge J. Nieva
Contact: Jorge J. Nieva Phone: 323-865-0451
Email not avaialable

Pasadena, California

Facility: Keck Medical Center of USC Pasadena
Investigator: Jorge J. Nieva
Contact: Jorge J. Nieva Phone: 323-865-0451
Email not avaialable

Sacramento, California

Facility: University of California Davis Comprehensive Cancer Center
Investigator: Jonathan W. Riess
Contact: Jonathan W. Riess Phone: 916-734-3089
Email not avaialable

New Haven, Connecticut

Facility: Smilow Cancer Center/Yale-New Haven Hospital
Investigator: Sarah B. Goldberg
Contact: Sarah B. Goldberg Phone: 855-476-4569
Email not avaialable

New Haven, Connecticut

Facility: Yale University
Investigator: Sarah B. Goldberg
Contact: Sarah B. Goldberg Phone: 203-785-5702
Email not avaialable

Tampa, Florida

Facility: Moffitt Cancer Center
Investigator: Peter A. Forsyth
Contact: Peter A. Forsyth Phone: 800-456-7121
Click HERE to send email to this center

Pittsburgh, Pennsylvania

Facility: University of Pittsburgh Cancer Institute (UPCI)
Investigator: Liza C. Villaruz
Contact: Liza C. Villaruz Phone: 412-647-8073
Email not avaialable