Exemestane in Post-Menopausal Women With NSCLC

• Status: Recruiting
• Trial end date: 2022-02-01
• Target enrollment: 0
• Participant gender: Female

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).

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Masonic Cancer Center, University of Minnesota
• Treatments: Exemestane

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