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Circulating FGF21 Levels and Efficacy of Exemestane, Everolimus and Metformin in Postmenopausal Women With Hormone Receptor Positive Metastatic Breast Cancer and BMI >/= 25


Phase 2
18 Years
N/A
Open (Enrolling)
Female
Breast Cancer

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Trial Information

Circulating FGF21 Levels and Efficacy of Exemestane, Everolimus and Metformin in Postmenopausal Women With Hormone Receptor Positive Metastatic Breast Cancer and BMI >/= 25


Study Drug Administration:

If you are found to be eligible to take part in this study, you will take an exemestane and
everolimus tablet by mouth every day. You will also take tablets of metformin by mouth 2
times a day. The drugs should be taken at about the same time each day.

The study drugs will be given in 28-day cycles.

Study Visits:

On Day 1:

- You will have a physical exam, including a measurement of your weight and vital signs.

- You will be asked about any side effects you may be having.

- You will be asked about any drugs you may have taken or may be taking.

- Your performance status will be recorded.

- Blood (about 1-2 teaspoons) will be drawn for routine tests.

- Blood (about 1 teaspoon) will be drawn for blood sugar tests. If you have a history of
diabetes, you will need to fast for 8 hours before these blood sugar tests.

At Weeks 4 and 12:

- You will have a physical exam, including a measurement of your vital signs.

- You will be asked about any side effects you may be having.

- You will be asked about any drugs you may have taken or may be taking.

- Blood (about 1-2 teaspoons) will be drawn for routine tests.

- Blood (about 1 teaspoon) will be drawn for blood sugar tests. If you have a history of
diabetes, you will need to fast for 8 hours before these blood sugar tests.

At Weeks 8, 16 and then every 2 months after that, and after your last dose of study drugs:

- You will have a physical exam, including a measurement of your vital signs.

- You will be asked about any side effects you may be having.

- You will be asked about any drugs you may have taken or may be taking.

- Blood (about 1-2 teaspoons) will be drawn for routine tests.

- Blood (about 4 teaspoons) will be drawn for biomarker testing (at weeks 8, 16 and 24
only).

- Blood (about 1 teaspoon) will be drawn for blood sugar tests. If you have a history of
diabetes, you will need to fast for 8 hours before these blood sugar tests.

- You will have imaging scans to check the status of the disease.

Length of Study:

You may continue taking the study drugs for as long as the doctor thinks it is in your best
interest. You will no longer be able to take the study drugs if the disease gets worse, if
intolerable side effects occur, or if you are unable to follow study directions.

This is an investigational study. Exemestane is FDA approved and commercially available for
the treatment of metastatic breast cancer. Metformin is FDA approved and commercially
available for the treatment of diabetes. Everolimus is FDA approved and commercially
available to treat metastatic breast cancer, advanced kidney cancer in some patients and a
certain type of brain tumor. The use of this drug combination is investigational.

Up to 40 patients will take part in this study. All will be enrolled at MD Anderson.


Inclusion Criteria:



1. Postmenopausal overweight or obese women with a history of biopsy-proven hormone
receptor-positive breast cancer and clinical evidence of metastatic disease.
Overweight is defined as body mass index (BMI) of 25 - 29.9 kg/m2 while obese is
defined as BMI >/= 30 kg/m2. Postmenopausal status is defined by one of the
following: a) no spontaneous menses for over 1 year, in women >/=55 years; b) no
spontaneous menses within the past 1 year in women < 55 years with postmenopausal
gonadotrophin levels (LH and FSH levels > 40 IU/L) or postmenopausal estradiol levels
(by local laboratory range); or c) bilateral oophorectomy.

2. Prior hormonal therapy for metastatic breast cancer is allowed. Patients who develop
progressive metastatic disease on a non-steroidal aromatase inhibitor are eligible.
Patients who develop metastatic disease while receiving a non-steroidal aromatase
inhibitor in the adjuvant setting are eligible.

3. One prior chemotherapy line for metastatic breast cancer is allowed if there is
evidence of progressive disease. Patients treated with chemotherapy to best response
and no evidence of progression are not eligible.

4. Prior tamoxifen, LH/RH agonist, anastrozole or letrozole therapy in the adjuvant
and/or neoadjuvant settings is allowed. Prior adjuvant and/or neoadjuvant
chemotherapy is allowed.

5. Patients must have: [1] at least one lesion that can be accurately measured in at
least one dimension >/= 20 mm with conventional imaging techniques or >/= 10 mm with
spiral CT or MRI; or [2] bone lesions: lytic or mixed (lytic + sclerotic) in the
absence of measurable disease; the following will be considered disease progression
among these patients: a) the appearance of one or more new lytic lesions in bone; b)
the appearance of one or more new lesions outside of bone; c) unequivocal progression
of existing bone lesions.

6. Localized radiotherapy, which does not influence the signal of evaluable lesion, is
allowed prior to the initiation of study medications.

7. ECOG performance status
8. Absolute neutrophil count (ANC) >/= 1000/microliter, platelets >/= 75,000/microliter,
hemoglobin >/= 8.5 gm/dL; creatinine clearance >60 mg/dL; bilirubin < 1.5 mg/dL ( 3 × ULN for patients known to have Gilbert Syndrome); ALT <3 x upper limit of normal
(or of normal; calcium
9. Fasting serum cholesterol 2.5 × ULN. In case one or both of these thresholds are exceeded, the patient can only
be included after initiation of statin therapy and when the above mentioned values
have been achieved.

10. Bisphosphonate treatment is permitted for the management of bone loss and/or bone
metastases.

11. Patients must be competent to give informed consent and to state that they understand
the investigational nature of the proposed treatment.

Exclusion Criteria:

1. HER2-overexpressing breast cancer (IHC 3+ staining or in situ hybridization
positive).

2. Diabetes mellitus on active treatment or hemoglobin A1C >/= 6.5% or random plasma
glucose > 200 mg/dL in patients without known diabetes.

3. Treatment with metformin in the 30 days prior to enrollment.

4. Known hypersensitivity or intolerance to metformin.

5. Previous treatment with exemestane or mTOR inhibitors.

6. Known hypersensitivity to mTOR inhibitors, e.g. sirolimus (rapamycin).

7. History of acromegaly, Cushing's syndrome, Cushing's disease, Addison's disease
(treated or untreated).

8. Patients with unstable angina, uncontrolled ischemic cardiac disease or symptomatic
congestive heart failure (e.g. Class III or IV New York Heart Association's
Functional Classification).

9. Other investigational drugs within the past 3 weeks or concurrently.

10. Patients with known chronic liver diseases (e.g., chronic active hepatitis, and
cirrhosis).

11. Another malignancy within 5 years prior to registration, with the exception of
adequately treated in-situ carcinoma of the cervix, uteri, basal or squamous cell
carcinoma or non-melanomatous skin cancer.

12. Radiotherapy within four weeks prior to registration except in case of localized
radiotherapy for analgesic purpose or for lytic lesions at risk of fracture which can
then be completed within two weeks prior to registration. Patients must have
recovered from radiotherapy toxicities.

13. History of brain or other central nervous system metastases.

14. Bilateral diffuse lymphangitic carcinomatosis.

15. Presence of life-threatening metastatic visceral disease, defined as extensive
hepatic involvement, or any degree of brain or leptomeningeal involvement (past or
present), or symptomatic pulmonary lymphangitic spread. Subjects with discrete
pulmonary parenchymal metastases are eligible, provided their respiratory function is
not compromised as a result of disease.

16. Patients receiving concomitant immunosuppressive agents or chronic corticosteroids
use, at the time of study entry except in cases outlined below: Topical applications
(e.g. rash), inhaled sprays (e.g. obstructive airways diseases), eye drops or local
injections (e.g. intra-articular) are allowed. Patients on stable low dose of
corticosteroids for at least two weeks before enrollment are allowed.

17. Any severe and / or uncontrolled medical conditions such as: Unstable angina
pectoris, symptomatic congestive heart failure, myocardial infarction prior to enrollment, serious uncontrolled cardiac arrhythmia; Uncontrolled diabetes
as defined by fasting serum glucose > 1.5 × ULN; Acute and chronic, active infectious
disorders (except for Hep B and Hep C positive patients) and nonmalignant medical
illnesses that are uncontrolled or whose control may be jeopardized by the
complications of this study therapy; Impairment of gastrointestinal function or who
have gastrointestinal disease that may significantly alter the absorption of study
drugs (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea,
malabsorption syndrome); Active skin, mucosa, ocular or GI disorders of Grade > 1

18. Significant symptomatic deterioration of lung function. If clinically indicated,
pulmonary function tests including measures of predicted lung volumes, DLco, O2
saturation at rest on room air will be considered to exclude restrictive pulmonary
disease, pneumonitis or pulmonary infiltrates.

19. Patients being treated with drugs recognized as being strong inhibitors or inducers
of the isoenzyme CYP3A (Rifabutin, Rifampicin, Clarithromycin, Ketoconazole,
Itraconazole, Voriconazole, Ritonavir, Telithromycin) within the last 5 days prior to
registration.

Type of Study:

Interventional

Study Design:

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Single Blind (Investigator), Primary Purpose: Treatment

Outcome Measure:

Progression-Free Survival (PFS)

Outcome Description:

Progression-free survival (PFS), defined as time from date of registration to date of first documented progression or death due to any cause. Tumor response assessed every 8 weeks (± 1 week) until disease progression and until further anti-cancer therapy is initiated.

Outcome Time Frame:

2 months

Safety Issue:

No

Principal Investigator

Francisco J. Esteva, MD,PHD

Investigator Role:

Principal Investigator

Investigator Affiliation:

UT MD Anderson Cancer Center

Authority:

United States: Food and Drug Administration

Study ID:

2011-1239

NCT ID:

NCT01627067

Start Date:

September 2012

Completion Date:

Related Keywords:

  • Breast Cancer
  • Breast Cancer
  • Hormone Receptor Positive Metastatic Breast Cancer
  • Hormone-sensitive
  • Postmenopausal
  • Body Mass Index
  • BMI
  • Everolimus
  • Afinitor
  • RAD001
  • Exemestane
  • Aromasin
  • Metformin
  • Breast Neoplasms

Name

Location

UT MD Anderson Cancer CenterHouston, Texas  77030