Exemestane in Treating Post-menopausal Patients with Recurrent or Advanced Non-small Cell Lung Cancer

This phase II trial studies how well exemestane works in treating post-menopausal patients with non-small cell lung cancer that has come back (recurrent) or that has spread to other places in the body and usually cannot be cured or controlled with treatment (advanced). Exemestane blocks an enzyme that helps create estrogen. It has been used in treating breast cancer and may also be effective in treating advanced lung cancer while causing fewer side effects than traditional chemotherapy.

Inclusion Criteria

• Recurrent or progressive advanced stage non-small cell lung cancer (no small cell component); NOTE: pathology reports documenting the diagnosis of NSCLC are required to be reviewed to confirm outside diagnosis
• Sufficient tumor tissue available from original diagnosis or subsequent biopsy for analysis of estrogen receptor and aromatase – tumor block or a minimum of 5 unstained slides
• Failed at least 1 prior chemotherapy regimen for advanced NSCLC
• Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
• Post-menopausal defined as * Age >= 55 years and 1 year or more of amenorrhea * Age < 55 years and 1 year or more of amenorrhea with an estradiol assay < 20 pg/mL * Surgical menopause with bilateral oophorectomy
• Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2
• Absolute neutrophil count (ANC) >= 1500/mm^3
• Platelets >= 100,000/mm^3
• Hemoglobin >= 8 g/dL
• International normalized ratio (INR) =< 1.5 or prothrombin time (PT)/partial thromboplastin time (PTT) within normal limits (WNL) of the institution
• Total bilirubin within normal institutional limits
• Aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase (SGOT) and alanine aminotransferase (ALT)/serum glutamic pyruvic transaminase (SGPT) =< 2.5 x upper limit of normal (ULN), except if there is known hepatic metastasis, wherein transaminases may be =< 5 x institutional ULN
• Serum creatinine =< 1.5 mg/dl or glomerular filtration rate > 50 ml/min
• Must have recovered to Common Terminology Criteria for Adverse Events (CTCAE) grade 1 or better from the acute effects of any prior surgery, chemotherapy or radiation therapy; chronic residual toxicity (i.e. peripheral neuropathy) is permitted
• A minimum time period must elapse between the end of a previous treatment and start of study therapy: * 1 week from the completion of radiation therapy for brain metastases * 4 weeks from the completion of chemotherapy or any experimental therapy * 4 weeks from prior major surgery (such as open biopsy or significant traumatic injury)
• Voluntary written consent before any research related procedures or therapy

Exclusion Criteria

• Known active central nervous system (CNS) disease - If patient has history of brain metastases, the brain lesions must have been treated with radiation and/or surgery- patients should be neurologically stable and on a stable or tapering dose of corticosteroids
• Inability or unwilling to swallow study drug
• Any gastrointestinal condition causing malabsorption or obstruction (eg, celiac sprue, gastric bypass surgery, strictures, adhesions, history of small bowel resection, blind loop syndrome)
• Currently using hormone replacement therapy (oral or patch) or/and phytoestrogen supplements (i.e. black cohosh)
• Known hypersensitivity to exemestane or its excipients
• Any serious underlying medical condition that, in the opinion of the enrolling physician, would impair the ability of the patient to receive protocol treatment
• Prior malignancy, with the exception of curatively treated squamous cell or basal carcinoma of the skin or in situ cervical cancer, unless there is a 3-year disease-free interval
• Concomitant use of strong cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) inducers such as rifampicin, phenytoin, carbamazepine, phenobarbital, or St. John’s wort

PRIMARY OBJECTIVES:

I. To determine a preliminary estimate of response of daily oral exemestane for the treatment of previously treated, advanced non-small cell lung cancer (NSCLC) in post-menopausal women.

SECONDARY OBJECTIVES:

I. To determine the toxicity profile of daily exemestane in this patient population.

II. To estimate the disease control rate, progression-free survival (PFS), and overall survival (OS) of exemestane for up to 1 year from study enrollment in post-menopausal women with previously treated advanced NSCLC.

III. To estimate quality of life at baseline and every 3 weeks while on study drug.

TERTIARY OBJECTIVES:

I. To conduct an exploratory biomarker correlative study of clinical outcome utilizing baseline tumor tissue and serum collected at baseline and serially during therapy.

II. To examine biomarkers in tissue post-treatment at the time of re-biopsy, if performed.

OUTLINE:

Patients receive exemestane orally (PO) once daily (QD) on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 4 weeks and for 1 year.

Lead Organization
University of Minnesota / Masonic Cancer Center

Principal Investigator
Manish Patel

Primary ID 2015LS095
Secondary IDs NCI-2015-02027
Clinicaltrials.gov ID NCT02666105