Phase I Dose Escalation Study of Carboplatin, Pemetrexed and Exemestane in Post-menopausal Women With Metastatic Non-squamous NSCLC
Inclusion Criteria:
- Ability to understand the purpose and risks of the study and provide signed and dated
informed consent and authorization to use protected health information (PHI)
- Histologically or cytologically confirmed, treatment-naive (or status post a single
treatment regimen of a tyrosine kinase inhibitor as a single agent) stage IV
non-squamous, NSCLC
- Measurable disease according to modified RECIST version 1.1
- Eastern Cooperative Oncology Group (ECOG) performance status =< 1
- Expected survival time of >= 3 months in the opinion of the investigator
- Postmenopausal women; women are eligible if they are postmenopausal (older than 50
years of age with no spontaneous menses for at least 12 months; or 50 years of age or
younger either with no spontaneous menses [amenorrheic] within 12 months of
randomization [e.g., spontaneous or secondary to hysterectomy] and a
follicle-stimulating hormone level within the postmenopausal range or with prior
bilateral oophorectomy)
- Ability to provide a formalin-fixed, paraffin-embedded (FFPE) tumor tissue sample
containing representative tumor tissue from a previously obtained biopsy/resection
that meets specific tissue sample requirements at screening
Exclusion Criteria:
- History of another primary cancer within 3 years prior to day 1 with the exception of
curatively treated skin cancer (other than melanoma) or curatively treated cervical
carcinoma in-situ
- Untreated central nervous system (CNS) involvement; (treated CNS involvement is
permitted only if the patient is not currently on steroid therapy or has remained on
a stable, unchanged dose of steroid for >= 3 weeks)
- Recent major surgery within the prior 4 weeks; (mediastinoscopy or placement of a
central venous access will be allowed as long as placement was more than 7 days prior
to receiving study drug)
- Any prior or concurrent investigational or standard therapy for treatment of
metastatic NSCLC including radiation therapy, chemotherapy, biological therapy (with
the exception of a single treatment regimen of a tyrosine kinase inhibitor as a
single agent, which must be completed 28 days prior to day 1), hormonal therapy, or
immunotherapy; (palliative-targeted radiotherapy for brain or bone metastases is
permitted providing it has been at least 14 days prior to day 1)
- History of hormone replacement therapy (estrogens with or without progestin) or an
aromatase inhibitor (anastrazole, letrozole, exemestane) within 8 weeks prior to day
1
- Osteoporosis complicated by pathologic fracture
- Concurrent investigational agents for non-malignant disease or prior investigational
agents for non-malignant disease within 4 weeks or 5 half-lives (whichever is
shorter) prior to day 1
- Concurrent cytotoxic or immunosuppressive therapy for non-malignant disease (e.g.,
for rheumatoid arthritis or lupus)
- Absolute neutrophil count (ANC) < 1500/mL
- Platelet count < 100,000/mL
- Hemoglobin < 9.0 g/dL
- Serum bilirubin > 1.5 x upper limits of normal (ULN)
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) > 2.5 x ULN (AST
and ALT > 5 x ULN for subjects with liver metastasis)
- Glomerular filtration rate (GFR) =< 50
- Albumin =< 2.5 g/dL
- Known history of or positive test result for human immunodeficiency virus (HIV)
- Active infection (including HIV/acquired immune deficiency syndrome [AIDS], hepatitis
B, or hepatitis C infection) requiring systemic antibiotics, antivirals, or
antifungals
- History of myocardial infarction within 12 months prior to day 1 or clinically
significant coronary disease
- New York Heart Association grade II or greater congestive heart failure
- Unstable coronary disease or clinically significant electrocardiogram (ECG) (12-lead)
abnormalities, as determined by the investigator
- Inability to comply with study and follow-up procedures
- Any other disease, metabolic dysfunction, physical examination finding, or clinical
laboratory finding that leads to reasonable suspicion of a disease or condition that
contraindicates the use of an investigational drug or that may affect the
interpretation of the results or render the subject at high risk from treatment
complications
- Other unspecified reasons that, in the opinion of the investigator or sponsor, make
the subject unsuitable for enrollment