Exemestane-RAD001-Metformin

NCT01627067 | Terminated Phase 2 Results FDA Drug

• 2 other identifiers: 2011-1239NCI-2012-01164
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Breast Cancer

Keywords

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

Outcome Measures

Primary Outcomes (2)

• 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.

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

• 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.

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

Study Arms (1)

Everolimus + Exemestane + Metformin

EXPERIMENTAL

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; Drug: Exemestane; Drug: Metformin

Interventions

Everolimus DRUG

10 mg by mouth once daily.

Also known as: Afinitor, RAD001

Everolimus + Exemestane + Metformin

Exemestane DRUG

25 mg by mouth once daily.

Also known as: Aromasin

Everolimus + Exemestane + Metformin

Metformin DRUG

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.

Everolimus + Exemestane + Metformin

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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).
• 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.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• Susan G. Komen Breast Cancer Foundation: collaborator

Study Sites (1)

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• University of Texas MD Anderson Cancer Center Website

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Everolimus; exemestane; Metformin

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals; Biguanides; Guanidines; Amidines

Results Point of Contact

• Title: Dr. Vicente Valero, MD/ Professor, Breast Medical Oncology
• Organization: UT MD Anderson Cancer Center

vvalero@mdanderson.org

713- 563-0751

Study Officials

• Vicente Valero, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 21, 2012
• First Posted: June 25, 2012
• Study Start: September 1, 2012
• Primary Completion: February 1, 2019
• Study Completion: February 1, 2019
• Last Updated: June 19, 2020
• Results First Posted: June 19, 2020

Record last verified: 2020-06

Locations

US (1)