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Breast CancerPhase 2NCT01627067

Exemestane-RAD001-Metformin

A Phase 2 study testing Everolimus, Exemestane and Metformin in people with Breast Cancer, run by M.D. Anderson Cancer Center at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 18 years and older, women only
Conditions the study is for
Breast Cancer
What is being tested?
Everolimus, Exemestane and Metformin
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
23 participants
Where
1 siteUnited States
Study dates
Sep 2012to 1 Feb 2019
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • Localized radiotherapy, which does not influence the signal of evaluable lesion, is allowed prior to the initiation of study medications.
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  • ECOG performance status </= 2.
  • 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.
  • 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.
  • Bisphosphonate treatment is permitted for the management of bone loss and/or bone metastases.
  • Patients must be competent to give informed consent and to state that they understand the investigational nature of the proposed treatment.

Who cannot join

  • HER2-overexpressing breast cancer (IHC 3+ staining or in situ hybridization positive).
  • Diabetes mellitus on active treatment or hemoglobin A1C >/= 6.5% or random plasma glucose > 200 mg/dL in patients without known diabetes.
  • Treatment with metformin in the 30 days prior to enrollment.
  • Known hypersensitivity or intolerance to metformin.
  • Previous treatment with exemestane or mTOR inhibitors.
  • Known hypersensitivity to mTOR inhibitors, e.g. sirolimus (rapamycin).
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  • History of acromegaly, Cushing's syndrome, Cushing's disease, Addison's disease (treated or untreated).
  • 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).
  • Other investigational drugs within the past 3 weeks or concurrently.
  • Patients with known chronic liver diseases (e.g., chronic active hepatitis, and cirrhosis).
  • 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.
  • 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.
  • History of brain or other central nervous system metastases.
  • Bilateral diffuse lymphangitic carcinomatosis.
  • 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.
  • 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.
  • 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
  • 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.
  • 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.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • University of Texas MD Anderson Cancer Center

    Houston, Texas, 77030

Other trials in United States

About this study

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

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.

Read more

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.

Read the detailed description

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.

Conditions
Breast Cancer
Being tested
Everolimus, Exemestane, Metformin
Keywords
Breast Cancer, Hormone Receptor Positive Metastatic Breast Cancer, Hormone-sensitive, Postmenopausal, Body Mass Index, BMI, Everolimus, Afinitor, RAD001, Exemestane, Aromasin, Metformin
Medical subject headings
Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • EverolimusDrug

    Also called Afinitor, RAD001

    10 mg by mouth once daily.

  • ExemestaneDrug

    Also called Aromasin

    25 mg by mouth once daily.

  • MetforminDrug

    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.

Study groups in NCT01627067
Study groupRoleWhat they receive
Everolimus + Exemestane + MetforminExperimentalPatients 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.
Receives: Drug: Everolimus; Drug: Exemestane; Drug: Metformin

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Progression-Free Survival (PFS)

    The primary end point of this study was progression-free survival (PFS), defined as the time from study enrollment to disease progression or death from any cause, whichever occurred first. Data for PFS were censored at the time of a patient's removal from study. All other analyses were post-hoc and should be regarded as such.

    Measured: From the registration until disease progression, death, unacceptable toxicity, or withdraw of study consent, whichever occurred first assessed up to 67 months

  2. Compare Progression Free Survival (PFS) Between the Number of Obese and Overweight Participants

    The primary end point of this study was progression-free survival (PFS), defined as the time from study enrollment to disease progression or death from any cause, whichever occurred first. Data for PFS were censored at the time of a participants removal from study. Compare PFS between overweight patients (n=11; BMI </=25 kg/m2) and obese patient ( n=11; BMI >/=25 kg/m2) on univariable cox regression analysis.

    Measured: From the registration until disease progression, death, unacceptable toxicity, or withdraw of study consent, whichever occurred first assessed up to 67 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted25 Jun 2012 (estimated)
  2. Study startSep 2012
  3. Primary completion1 Feb 2019
  4. Study completion1 Feb 2019

Why it stopped: Komen Foundation Funding Terminated

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
23 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01627067
Sponsor's protocol ID
2011-1239
Other IDs
NCI-2012-01164
Status last verified
Jun 2020
First submitted
21 Jun 2012
Last updated
19 Jun 2020
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Everolimus, Exemestane and Metformin in people with Breast Cancer, run by M.D. Anderson Cancer Center at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 19 Jun 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 19 Jun 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression-Free Survival (PFS) (time frame: From the registration until disease progression, death, unacceptable toxicity, or withdraw of study consent, whichever occurred first assessed up to 67 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01627067.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Jun 2020; AzTrials last refreshed its copy on 1 Nov 2026.

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