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The Impact of Obesity and Obesity Treatments on Breast Cancer: A Phase I Trial of Exemestane With Metformin and Rosiglitazone for Postmenopausal Obese Women With ER+ Metastatic Breast Cancer

Phase 1
18 Years
Not Enrolling
Breast Cancer

Thank you

Trial Information

The Impact of Obesity and Obesity Treatments on Breast Cancer: A Phase I Trial of Exemestane With Metformin and Rosiglitazone for Postmenopausal Obese Women With ER+ Metastatic Breast Cancer

The Study Drugs:

Exemestane decreases the ability of estrogen to help cancer cells grow. This could cause
the cancer cells to die.

Avandamet contains two drugs commonly used to control blood sugar levels in patients with
diabetes (metformin and rosiglitazone).

If you are found to be eligible to take part in this study, the dose of Avandamet you
receive will depend on when you joined this study. The first group of participants will
receive the lowest dose level of Avandamet. Each new group will receive a higher dose of
Avandamet than the group before it, if no intolerable side effects were seen. This will
continue until the highest tolerable dose of Avandamet is found.

All participants will receive the same dose level of exemestane.

Study Drug Administration:

The study drug(s) will be given in 28-day "cycles."

You will take an exemestane tablet by mouth every day. You will also take tablets of
Avandamet by mouth 1 or 2 times a day depending on the dose level to which you are assigned.
You should take Avandamet at meals.

Study Visits:

On Day 1 of Cycles 2, 3, and 4, and then every 3 months after that, the following tests and
procedures will be performed:

- 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.

- You will have a performance status evaluation.

- Blood (about 1-2 teaspoons) will be drawn for routine tests. This blood draw can be
done up to 3 days before each cycle.

- Blood (about 1 teaspoons) 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.

Every 3 months, you will have scans to check the status of the disease. The scan performed
will depend on where the disease is located in the body.

Every 3 months, you will also have an echocardiogram (ECHO) or a multi-gated acquisition
(MUGA) scan to test your heart function.

Additional Blood Draws:

Blood (about 1 teaspoon each time) will also be drawn for pharmacokinetic (PK) testing. PK
testing measures the amount of study drug(s) in the body at different time points. Blood
will be drawn for PK testing before you take the study drug(s) and 1, 3, 6, 12, and 23 hours
after you take the study drug(s) on Days 1, 8, and 15 of Cycle 1.

Length of Study:

You may take the study drug(s) for as long as the disease is stable and/or responding. You
may be taken off study if the disease gets worse or intolerable side effects occur.

This is an investigational study. Exemestane and Avandamet are FDA approved and
commercially available. Exemestane is approved for the treatment of metastatic breast
cancer. Avandamet is approved for the treatment of diabetes. The use of this drug
combination is investigational.

Up to 24 patients will take part in this study. All will be enrolled at M. D. Anderson.

Inclusion Criteria:

1. Overweight or obese postmenopausal women with a history of biopsy-proven estrogen
receptor positive and/or progesterone receptor positive breast cancer and clinical
evidence of metastatic disease. Overweight and obesity are defined by the WHO as a
BMI of 25 - 29.9 and >/= 30 kg/m^2 respectively. Postmenopausal status is defined by
one of the following: a) no spontaneous menses for over 1 year, in women >55 years;
Continued in inclusion criterion # 2.

2. Continuation from inclusion #1: b) no spontaneous menses within the past 1 year in
women 40
IU/L) or postmenopausal estradiol levels (<10 pg/mL); or c) bilateral oophorectomy.

3. Prior endocrine therapy, biologic therapy and chemotherapy are allowed, either in the
adjuvant setting or for metastatic breast cancer.

4. Prior exemestane, metformin, or rosiglitazone is allowed if taken longer than 7 days
prior to enrollment.

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

6. Performance status
7. Absolute neutrophil count (ANC) >/= 1000/µl, platelets >/= 75,000/µl, hemoglobin >/=
8.5 gm/dL; serum creatinine < 1.4 mg/dL; bilirubin < 1.8 mg/dL; ALT or AST ULN if no demonstrable liver metastases or metastases; alkaline phosphatase < 3 x upper limit of normal; calcium
8. Patients must be competent to give informed consent and to state that they understand
the investigational nature of the proposed treatment.

Exclusion Criteria:

1. Extensive radiotherapy within previous 4 weeks (greater than or equal to 30% of
marrow-bearing bone, e.g., whole pelvis or half spine).

2. Uncontrolled diabetes mellitus (hemoglobin A1C > 9 or random plasma glucose > 400

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

4. 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).

5. Concurrently receiving and are unwilling to discontinue hormonal (estrogen with or
without progesterone) replacement therapy.

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

7. Patients with known chronic liver disease (i.e., chronic active hepatitis, and

8. Laboratory results sustained at: International normalized ratio (INR) > 1.6; ALT or
AST > 2.5 x ULN if no demonstrable liver metastases or > 5 x ULN in presence of liver
metastasis; No more than 3 retests within screening period

9. Patients with known diagnosis of human immunodeficiency virus (HIV) infection.

10. Patients who received chemotherapy within 3 weeks (6 weeks for nitrosourea or
mitomycin-C). Acute toxicities from prior therapy must have resolved to Grade with the exception of fatigue, alopecia, or anemia.

11. Any severe concomitant condition which makes it undesirable for the patient to
participate in the study or which would jeopardize compliance with the protocol e.g.,
severe renal or hepatic impairment or currently unstable or uncompensated respiratory
or cardiac conditions.

12. History of hypersensitivity to active or inactive excipients of the study medications
- exemestane or metformin.

13. Untreated or clinically unstable central nervous system involvement. A patient with
adequately treated brain metastases would be eligible one month after completion of
surgery and/or radiation therapy if she is clinically stable.

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Dose-limiting toxicity (DLT)

Outcome Time Frame:

Day 1 of each cycle

Safety Issue:


Principal Investigator

Francisco J. Esteva, MD, PhD

Investigator Role:

Study Chair

Investigator Affiliation:

UT MD Anderson Cancer Center


United States: Institutional Review Board

Study ID:




Start Date:

July 2009

Completion Date:

Related Keywords:

  • Breast Cancer
  • Breast
  • Obese
  • Obesity Treatment
  • Exemestane
  • Aromasin
  • Metformin and Rosiglitazone
  • Avandamet
  • Postmenopausal
  • Hormone-sensitive
  • Hormone-receptive-positive breast cancer
  • Breast Neoplasms
  • Obesity



UT MD Anderson Cancer CenterHouston, Texas  77030