Overview

The Impact of Obesity and Obesity Treatments on Breast Cancer

Status:
Completed

Trial end date:
2012-08-01

Target enrollment:
0

Participant gender:
Female

Summary

The goal of this clinical research study is to find the highest tolerable dose of Avandamet that can be given in combination with exemestane to patients who are obese and postmenopausal with hormone-receptive-positive breast cancer that has spread to other parts of the body.

Phase:

Phase 1

Accepts Healthy Volunteers?

Details

Lead Sponsor:

M.D. Anderson Cancer Center

Collaborator:

Susan G. Komen Breast Cancer Foundation

Treatments:

Exemestane
Metformin
Rosiglitazone

Criteria

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
mg/dL).

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
cirrhosis).

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.