Exemestane in Post-Menopausal Women With NSCLC

Study Overview
=================
Brief Summary
-----------------
This is a phase II therapeutic study of adding exemestane therapy in post-menopausal women with advanced non-small cell lung cancer (NSCLC) who are progressing while on treatment with an immune checkpoint antibody (pembrolizumab, atezolizumab, or nivolumab).

Official Title
-----------------
Phase II Trial of Exemestane in Previously Treated Post-Menopausal Women With Advanced Non-Small Cell Lung Cancer

Conditions
-----------------
Non-Small Cell Lung Cancer

Intervention / Treatment
-----------------
* Drug: Exemestane


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria Recurrent or progressive advanced stage non-small cell lung cancer (no small cell component) with most recent treatment being an 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. Patients with EGFR/ALK/ROS1 rearrangements should have received an FDA-approved TKI prior to enrollment on this trial. Measureable disease by 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 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 Adequate organ function within 14 days of study enrollment defined as: Hematology: ** Absolute neutrophil count (ANC) ≥ 1500/mm³, Platelets ≥ 100,000/mm³, Hemoglobin ≥ 8 g/dL Biochemistry: Total Bilirubin within normal institutional limits AST/SGOT and ALT/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 CTCAE 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 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 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 (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 CYP3A4 inducers such as rifampicin, phenytoin, carbamazepine, phenobarbital, or St. John's wort as these may significantly reduce the availability of exemestane
Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Exemestane Therapy<br> | Drug: Exemestane<br>* One 25 mg tablet once daily for a minimum of 6 weeks<br>* Other names: Aromasin;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease Response (RECIST) | Initial disease response will be assessed from 6 weeks to 1 year after the start of exemestane using the Response Criteria in Solid Tumors (RECIST). Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. | 6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Toxicity Assessment | Toxicity will be assessed from the 1st dose to Post Treatment Day 30, up to 22 weeks. Toxicity severity will be graded using the Common Toxicity Criteria for Adverse Events (CTCAE) version 4. | Post Treatment Day 30 | 
| Progression-free Survival | progression-free survival will be assessed until 1 year after study enrollment based on the definitions found in RECIST 1.1 | 1 year after enrollment | 
| Quality of Life Assessment | Quality of life will be assessed by use of Patient-Reported Outcomes Measurement Information System 29 (PROMIS-29) at baseline, every 3 weeks from the 1st dose to Post Treatment Day 30, up to 22 weeks. Patient's report on a number of subjects on a 0-10 scale. The scores range from 28 to 150. 50 is the average score, 28 is the best health and 150 is the worst health. | Baseline, Treatment, End of Treatment, and 1 Month Post-Treatment | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
NSCLC