FJE_Exemestane-RAD001-Metformin

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Susan G. Komen Breast Cancer Foundation
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT01627067
First received: June 21, 2012
Last updated: July 14, 2014
Last verified: July 2014
  Purpose

The goal of this clinical research study is to learn if exemestane and everolimus combined with metformin can help to control breast cancer in patients who are obese or overweight and post-menopausal with hormone-receptor-positive breast cancer that has spread to other parts of the body.

Exemestane is designed to decrease the ability of estrogen to help cancer cells grow. This could cause the cancer cells to die.

Metformin is commonly used to control blood sugar levels in patients with diabetes. It is designed to lower insulin levels, which may slow or stop the growth of breast cancer cells.

Everolimus is designed to block cells from dividing. This may cause cancer cells to die. Everolimus may also stop the growth of new blood vessels that help tumors grow.


Condition Intervention Phase
Breast Cancer
Drug: Everolimus
Drug: Exemestane
Drug: Metformin
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Single Blind (Investigator)
Primary Purpose: Treatment
Official Title: Circulating FGF21 Levels and Efficacy of Exemestane, Everolimus and Metformin in Postmenopausal Women With Hormone Receptor Positive Metastatic Breast Cancer and BMI >/= 25

Resource links provided by NLM:


Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:
  • Progression-Free Survival (PFS) [ Time Frame: 2 months ] [ Designated as safety issue: No ]
    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.


Estimated Enrollment: 40
Study Start Date: September 2012
Estimated Primary Completion Date: September 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Everolimus + Exemestane + Metformin
Patients take one 25 mg tablet of exemestane once daily, everolimus 10 mg orally per day and metformin 500 mg orally per day for three days. If there are no dose limiting toxicities, dose of metformin will be increased by 500 mg orally every three days to reach the target dose of 1,000 mg orally twice daily. Drugs will be taken immediately after a meal at the same time each day.
Drug: Everolimus
10 mg by mouth once daily.
Other Names:
  • Afinitor
  • RAD001
Drug: Exemestane
25 mg by mouth once daily.
Other Name: Aromasin
Drug: Metformin
500 mg by mouth per day for three days. If there are no dose limiting toxicities, the dose of metformin will be increased by 500 mg orally every three days to reach the target dose of 1,000 mg orally twice daily.

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  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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 </= 2.
  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 </= 5 if hepatic metastases are present); alkaline phosphatase < 3 x upper limit of normal; calcium </= 11.0 mg/dL.
  9. Fasting serum cholesterol </= 300 mg/dl or 7.75 mmol/L and fasting triglycerides </= 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 </= 6 months 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01627067

Locations
United States, Texas
UT MD Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
Susan G. Komen Breast Cancer Foundation
Investigators
Principal Investigator: Vicente Valero, MD M.D. Anderson Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT01627067     History of Changes
Other Study ID Numbers: 2011-1239, NCI-2012-01164
Study First Received: June 21, 2012
Last Updated: July 14, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by M.D. Anderson Cancer Center:
Breast Cancer
Hormone Receptor Positive Metastatic Breast Cancer
Hormone-sensitive
Postmenopausal
Body Mass Index
BMI
Everolimus
Afinitor
RAD001
Exemestane
Aromasin
Metformin

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Metformin
Exemestane
Sirolimus
Everolimus
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Aromatase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents

ClinicalTrials.gov processed this record on August 28, 2014