Exemestane in Treating Post-menopausal Patients with Recurrent or Advanced Non-small Cell Lung Cancer
Inclusion Criteria
- Recurrent or progressive advanced stage non-small cell lung cancer (no small cell component) with most recent treatment being a Food and Drug Administration (FDA) approved immune checkpoint inhibitor (pembrolizumab, atezolizumab, or nivolumab); 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 FDA approved treatment 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
- Life expectancy of 3 months or more in the opinion of the enrolling investigator and documented in the medical record
- Absolute neutrophil count (ANC) >= 1500/mm^3 (within 14 days of study enrollment)
- Platelets >= 100,000/mm^3 (within 14 days of study enrollment)
- Hemoglobin >= 8 g/dL (within 14 days of study enrollment)
- Total bilirubin within normal institutional limits (within 14 days of study enrollment)
- 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 (within 14 days of study enrollment)
- Serum creatinine =< 1.5 mg/dl or glomerular filtration rate > 50 ml/min (within 14 days of study enrollment)
- Must have recovered to Common Terminology Criteria for Adverse Events (CTCAE) version (v) 4 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 requiring =< 10mg oral prednisone equivalence of steroids per day
- Any toxicity from immune-related toxicity from prior immune therapy that would preclude further treatment with anti-PD-1/PDL-1 inhibitor or ongoing immune-related (IR) toxicity >= grade 2
- Requiring > 10 mg prednisone equivalence of steroids per day for immune-related toxicity
- Inability or unwilling to swallow study drug
- Any gastrointestinal condition causing malabsorption or obstruction (e.g., 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 CYP3A4 inducers such as rifampicin, phenytoin, carbamazepine, phenobarbital, or St. John’s wort as these may significantly reduce the availability of exemestane
Minnesota
Minneapolis
PRIMARY OBJECTIVE:
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 receiving and progressing on immune checkpoint blockade (ICB) therapy.
SECONDARY OBJECTIVES:
I. To determine the toxicity profile of daily exemestane in combination with immune checkpoint blockade therapy 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 during study treatment and for one month following discontinuation of study treatment.
CORRELATIVE OBJECTIVES:
I. To conduct an exploratory biomarker correlative study of clinical outcome utilizing archival 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.
III. To examine serum biomarkers of the peripheral immune response after aromatase inhibition.
OUTLINE:
Patients receive exemestane orally (PO) once daily (QD) on days 1-21. Cycles 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.
Trial Phase Phase II
Trial Type Treatment
Lead Organization
University of Minnesota / Masonic Cancer Center
Principal Investigator
Manish Patel
- Primary ID 2015LS095
- Secondary IDs NCI-2015-02027
- Clinicaltrials.gov ID NCT02666105