Clinical trial NCT02666105: Exemestane in Post-Menopausal Women With NSCLC
Official title: Phase II Trial of Exemestane in Previously Treated Post-Menopausal Women With Advanced Non-Small Cell Lung Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Non-Small Cell Lung Cancer
Keywords: NSCLC
Lead sponsor: Masonic Cancer Center, University of Minnesota
Sponsor class: OTHER
First posted: 2016-01-28
Enrollment: 6
Sex: FEMALE
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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).


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

Primary outcomes:
measure: Disease Response (RECIST)
timeFrame: 6 weeks
Secondary outcomes:
measure: Toxicity Assessment
timeFrame: Post Treatment Day 30
measure: Progression-free Survival
timeFrame: 1 year after enrollment
measure: Quality of Life Assessment
timeFrame: Baseline, Treatment, End of Treatment, and 1 Month Post-Treatment
Other outcomes:
Locations:
city: Albert Lea
country: United States
facility: Mayo Clinic Health System
state: Minnesota
city: Brainerd
country: United States
facility: Essentia Health St. Joseph's Medical Center
state: Minnesota
city: Deer River
country: United States
facility: Essentia Health Deer River
state: Minnesota
city: Detroit Lakes
country: United States
facility: Essentia Health St. Mary's Detroit Lakes
state: Minnesota
city: Duluth
country: United States
facility: Essentia Health Cancer Center
state: Minnesota
city: Fosston
country: United States
facility: Essentia Health Fosston
state: Minnesota
city: Grand Rapids
country: United States
facility: Fairview Grand Itasca Clinic & Hospital
state: Minnesota
city: Hibbing
country: United States
facility: Essentia Health Hibbing
state: Minnesota
city: Hibbing
country: United States
facility: Fairview Range Medical Center
state: Minnesota
city: Mankato
country: United States
facility: Mayo Clinic Health System
state: Minnesota
city: Minneapolis
country: United States
facility: Masonic Cancer Center, University of Minnesota
state: Minnesota
city: Monticello
country: United States
facility: Monticello Cancer Center (MMCORC)
state: Minnesota
city: Park Rapids
country: United States
facility: Essentia Health Park Rapids
state: Minnesota
city: Princeton
country: United States
facility: Fairview Northland Medical Center
state: Minnesota
city: Sandstone
country: United States
facility: Essentia Health Sandstone
state: Minnesota
city: Thief River Falls
country: United States
facility: Sanford Thief River Falls Medical Center
state: Minnesota
city: Virginia
country: United States
facility: Essentia Health Virginia
state: Minnesota
city: Worthington
country: United States
facility: Sanford Worthington Medical Center
state: Minnesota
Study officials:
affiliation: University of Minnesota Masonic Cancer Center
name: Manish Patel, DO
role: PRINCIPAL_INVESTIGATOR
References: