Inclusion Criteria:
- Histologically or cytologically confirmed metastatic stage IIIB/IV lung adenocarcinoma
with known activating mutations in the EGFR TK domain (including exon 19 deletion and
L858R)
- Prior EGFR TKI therapy with progression, and documented EGFR T790M mutation on tumor
biopsy; however, this need not be only second line
- Measurable disease defined as lesions that can be accurately measured in at least one
dimension (longest diameter to be recorded) as ≥ 10 mm with CT scan, as ≥ 20 mm by
chest x-ray, or ≥ 10 mm with calipers by clinical exam.
- At least 18 years of age.
- ECOG performance status ≤ 2
- Normal bone marrow and organ function as defined below:
- Leukocytes ≥ 3,000/mcL
- Absolute neutrophil count ≥ 1,500/mcl
- Platelets ≥ 100,000/mcl
- Hemoglobin ≥ 9.0 g/dL
- INR ≤ 2.0
- Total bilirubin ≤ 1.5 x IULN
- AST(SGOT)/ALT(SGPT) ≤ 3.0 x IULN
- Creatinine ≤ IULN OR creatinine clearance ≥ 45 mL/min/1.73 m2 for patients with
creatinine levels above institutional normal
- Potassium within institutional limits (supplementation allowed)
- Magnesium within normal limits (supplementation allowed)
- Tumor tissue available and deemed adequate for genomic studies.
- Women of childbearing potential and men must agree to use adequate contraception
(hormonal or barrier method of birth control, abstinence) prior to study entry and for
the duration of study participation. Should a woman become pregnant or suspect she is
pregnant while participating in this study, she must inform her treating physician
immediately.
- Ability to understand and willingness to sign an IRB approved written informed consent
document (or that of legally authorized representative, if applicable).
Exclusion Criteria:
- A history of other malignancy ≤ 5 years previous with the exception of basal cell or
squamous cell carcinoma of the skin which were treated with local resection only or
carcinoma in situ of the cervix.
- Currently receiving any other investigational agents.
- Received therapeutic oral or IV antibiotics within 2 weeks prior to first day of study
treatment. Patients receiving prophylactic antibiotics (e.g., to prevent a urinary
tract infection or chronic obstructive pulmonary disease exacerbation) are eligible.
- Symptomatic, untreated or unstable central nervous system or leptomeningeal
metastases. (Patients with treated and stable brain metastases (confirmed by 2 scans
at least 4 weeks apart), with no evidence of cavitation or hemorrhage in the brain
lesion are eligible provided that they are asymptomatic and do not require
corticosteroids.)
- A history of allergic reactions attributed to compounds of similar chemical or
biologic composition to rociletinib or other agents used in the study.
- Currently receiving treatment with any medication that has the potential to prolong
the QT interval and the treatment cannot be discontinued or switched to a different
medication.
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, myocardial
infarction within the previous 3 months, coronary angioplasty or stenting or bypass
grafting within the past 6 months, cardiac ventricular arrhythmias requiring
medication, any history of 2nd or 3rd degree atrioventricular conduction defects,
cardiac arrhythmia, or psychiatric illness/social situations that would limit
compliance with study requirements.
- History of interstitial lung disease.
- History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis
obliterans), drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active
pneumonitis on screening chest CT scan. History of radiation pneumonitis in the
radiation field (fibrosis) is permitted.
- Class II to IV heart failure as defined by the New York Heart Association functional
classification system. Patients with known coronary artery disease, congestive heart
failure not meeting the above criteria, or LVEF < 50% must be on a stable medial
regimen that is optimized in the opinion of the treating physician, in consultation
with a cardiologist if appropriate, to be eligible.
- Any of the following cardiac abnormalities or history:
- Clinically significant abnormal 12-lead ECG, QT interval corrected using
Fridericia's method (QTcF) > 450 msec
- Inability to measure QT interval on ECG
- Personal or family history of long QT syndrome
- Implantable pacemaker or implantable cardioverter defibrillator
- Resting bradycardia < 55 beats/min
- Pregnant and/or breastfeeding. Women of childbearing potential must have a negative
pregnancy test within 7 days of study entry.
- Known HIV-positivity on combination antiretroviral therapy because of the potential
for pharmacokinetic interactions with rociletinib. In addition, these patients are at
increased risk of lethal infections when treated with marrow-suppressive therapy.
Appropriate studies will be undertaken in patients receiving combination
antiretroviral therapy when indicated.
- Active hepatitis B virus (HBV) defined by positive hepatitis B surface antigen (HBsAg)
test at screening. Patients with past or resolved HBV infection (defined by a negative
HBsAg test and a positive anti-hepatitis B core antigen (anti-HBc) antibody test) are
eligible. HBV DNA must be obtained in these patients prior to first day of study
treatment.
- Active hepatitis C virus (HCV). Patients positive for HCV antibody are eligible only
if PCR is negative for HCV RNA.
- Active tuberculosis.
- Presence of active GI disease (including GI bleeding or ulceration) or other condition
that could affect GI absorption) (e.g. malabsorption syndrome, history of biliary
tract disease).
