Neoplasms

All Conditions

Symptoms and General Pathology

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Carcinoma

Recurrence

Endometrial Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Uterine Neoplasms

Genital Neoplasms, Female

Urogenital Neoplasms

Uterine Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Hypoglycemic Agents

All Drugs and Chemicals

Antineoplastic Agents

Anti-Infective Agents

Metformin

Everolimus

Letrozole

Sirolimus

Temsirolimus

MTOR Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Immunosuppressive Agents

Immunologic Factors

Aromatase Inhibitors

Estrogens

Estrogen Antagonists

Estrogen Receptor Antagonists

Hormones

Hormone Antagonists

Patients have a 7-10 day lead in period where they take Metformin alone. The starting dose of Metformin 500 mg by mouth daily for 4 days and then increased to 500 mg by mouth twice a day. Everolimus and Letrozole added and considered the start of Cycle #1.

Everolimus administered by mouth as once daily dose of 10 mg. Letrozole 2.5 mg tablet by mouth once daily. The oral dose of Everolimus should be taken together with the daily dose of Letrozole 2.5mg.

500 mg by mouth daily for 4 days on Days 1 - 4 of Cycle 0 and then 2 times a day (about 12 hours apart) every day after that. Metformin taken for 7 - 10 days in Cycle 0 before Cycle 1 begins.

2.5 mg tablet by mouth once daily in a 28 day cycle.

10 mg by mouth once daily in a 28 day cycle.

Pamela Soliman, MD

The goal of this clinical research study is to learn if the combination of everolimus, letrozole, and metformin can help to control recurrent or progressive endometrial cancer. The safety of this drug combination will also be studied.

Everolimus is designed to block a protein inside cancer cells that is involved in cancer growth.

Letrozole is designed to block a protein from making estrogen. This may interfere with the growth of cancer cells.

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 endometrial cancer cells.

Study Drug Administration:

If you are found to be eligible to take part in this study and you are not already taking metformin, you will take metformin before you begin the regular study cycles (Cycles 1 and beyond). This will be called "Cycle 0." You will take metformin by mouth 1 time a day on Days 1-4 of Cycle 0 and then 2 times a day (about 12 hours apart) every day after that. You will take metformin for 7-10 days in Cycle 0 before Cycle 1 begins. If you are already taking metformin, you will continue your regular dose and start Day 1 of Cycle 1. If you are already taking metformin but your dose is less than 1000mg/day, your dose will be slowly raised up to the study dose over the course of 7-10 days and then you will start Cycle 1. In Cycles 1 and beyond, all participants will take all 3 drugs at a time. You should take metformin with food.

Starting in Cycle 1, you will take everolimus 1 time a day by mouth at about the same time every day. You should take it either consistently with food every day or consistently without food every day.

Starting in Cycle 1, you will take letrozole 1 time a day by mouth at about the same time every day.

It is very important for you to take the study drugs just as the study doctor tells you. Do not skip any doses unless your study doctor tells you to skip doses. If you throw up after taking the study drugs, you should NOT take another tablet that day. Let your study doctor know that you got sick. If you forget to take the study drugs one day, do not take any extra doses the next day. Call your study doctor and ask for advice.

There are 4 weeks in each cycle (except Cycle 0).

Study Visits:

Every cycle (+/- 10 days):

* You will have a physical exam, including measurement of your vital signs and weight.
* Your performance status will be recorded.
* You will be asked about any side effects you may have had.
* Blood (about 2 tablespoons) will be drawn for routine tests.
* If the doctor thinks it is needed, blood (about 1 teaspoon) will be drawn to check for hepatitis.

After Cycles 2, 4, and 6 and then every 3 cycles after that (Cycles 9, 12, 15, and so on) (+/- 10 days):

* You will have scans such as a CT scan and/or MRI to check the status of the disease.
* If you have chest disease, you will have a CT scan of the chest.
* If the disease could be felt in the pelvis at the beginning of the study, you will have a pelvic exam

After every other cycle (Cycles 2, 4, and so on), blood (about 1 teaspoon) will be drawn for routine tests.

Length of Treatment:

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.

Your participation on the study will be over after the follow-up visits.

End-of-Treatment Visit:

Within 4 weeks after the last dose of study drugs:

* You will have a physical exam, including a pelvic exam and measurement of your vital signs and weight.
* Your performance status will be recorded.
* You will be asked about any side effects you may have had.
* Blood (about 2 tablespoons) will be drawn for routine tests.
* You will have scans such as a CT scan and/or MRI to check the status of the disease.
* If you have chest disease, you will have a CT scan of the chest.

Follow-Up:

You will have follow-up visits as often as the doctor thinks is needed. At every visit:

* You will have a physical exam, including measurement of your vital signs.
* Your performance status will be recorded.
* You will be asked about any side effects you may have had.
* If the doctor thinks it is needed, you will have scans such as a CT scan and/or MRI to check the status of the disease.
* If you have chest disease, you will have a CT scan of the chest.

As often as the doctor thinks is needed, the study staff will call you to ask about side effects you may have had. These calls should last 5-10 minutes.

.

This is an investigational study. Everolimus is FDA approved and commercially available to treat kidney, breast, and pancreatic cancers. Letrozole is FDA approved and commercially available to treat breast cancer and ovarian cancer. Metformin is FDA approved and commercially available to treat diabetes. The combination of everolimus, metformin, and letrozole in this study to treat endometrial cancer is investigational.

Up to 64 patients will be enrolled in this study. Up to 59 may take part at MD Anderson. Up to 5 patients per site may be enrolled at MD Anderson Cooper and Spartanburg Regional Healthcare System and Harris Health System.

A Phase II, Single-Arm Study of RAD001 (Everolimus), Letrozole, and Metformin in Patients With Advanced or Recurrent Endometrial Carcinoma

Clinical benefit rate (CBR) determined by combining the complete response rate, partial response rate, and stable disease rate. Response evaluated by repeat imaging (CT or MRI) using RECIST 1.1 at the completion of the second cycle (8 weeks + 7 days of treatment).

Survival determined by measuring the time from study entry (1st treatment) to progression (PFS) or death (OS). Progression-free survival (PFS) and overall survival (OS) estimated with the Kaplan-Meier product-limit estimator.

Novartis

National Cancer Institute (NCI)

M.D. Anderson Cancer Center

Gland and Hormone Related Diseases

Rare Diseases

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Fallopian Tube Neoplasms

Endocrine Gland Neoplasms

Ovarian Diseases

Adnexal Diseases

Endocrine System Diseases

Gonadal Disorders

Fallopian Tube Diseases

Ovarian Cancer

Ovarian Epithelial Cancer

Fallopian Tube Cancer

John J. Kavanagh, MD

Primary Objectives:

* To determine the objective response rate of Letrozole when administered to patients with advanced or recurrent borderline tumors or low-grade epithelial cancers from the ovary , fallopian tube or peritoneum.
* To determine the time to tumor progression of patients with advanced or recurrent borderline tumors or low-grade epithelial cancers from the ovary, fallopian tube or peritoneum.
* To identify the biological markers to predict response to Letrozole and study the aspects of the hormones in these types of tumors.

Letrozole is an anticancer hormone that is FDA approved for use in patients with advanced breast cancer.

Before you can be enrolled in this study, you must go through some screening tests to make sure you are eligible. The screening tests include a complete medical history and physical exam, including measurement of your pulse rate, breathing rate, temperature, height, weight, and blood pressure. The physical examination will also include measurement of any visible cancer lesions. You will be asked what medications you are taking, including over the counter medications, herbal medications, and vitamins. You will have chest x-rays and/or CT or MRI scans to measure the size of your tumors. You will have routine blood tests (about 2 and a 1/2 tablespoons) performed.

If you qualify for the study, you will take Letrozole once a day by mouth. Letrozole will be dispensed in the form of a tablet. Four to eight weeks worth of Letrozole will be prescribed to you by your treatment doctor at each visit. You will continue to receive Letrozole as long as you are responding to treatment.

You will be required to come back for check-up at least once every 2 months while on study for the first two years. You should contact the study doctor if you feel unwell or feel the need to see the doctor before your appointment earlier than your designated appointment.

At each follow-up visit, you will have a complete physical exam. The chest x-rays and/or CT or MRI scans will be repeated every 2 months, and at the time you complete the trial, or at any other time if necessary. Blood tests (about 1 tablespoon) will be performed every 2 months. Information about the medications you are taking, or medical problems you have had since your last visit will be collected. At each follow-up visit, you will also be asked to complete a one page, paper and pencil check off sheet. You will be asked to identify symptoms you may be having and to note the amount of distress each symptom is causing you.

You will be taken off study if the disease gets worse or intolerable side effects occur and your doctor will discuss possible treatment options with you.

However, as long as you continue to benefit from Letrozole treatment, you will continue on this treatment. If you are on letrozole treatment beyond two years, you will be followed up at three months interval. At these follow up visits, you will be asked questions about your medical history and have a physical exam. You will also have blood (about tablespoon) and urine tests, and/or radiological evaluation of the tumor. As long as you continue to benefit from letrozole treatment, you will be followed up.

Your status will be followed for as long as possible even after you are taken off the study drug. You will be contacted by phone or asked to come to the clinic for a routine visit. You will be contacted every 6 weeks for 1 year after the study and every 12 weeks for the rest of your life.

This is an investigational study. Letrozole is not approved by the FDA for the treatment of recurrent low grade or borderline ovarian, fallopian tube or primary peritoneal cancer. A total of up to 80 patients will take part in this study. All will be enrolled at M. D. Anderson.

Letrozole in Patients With Ovarian Tumors

Phase II Study of Letrozole in Patients With Recurrent Advanced Borderline Tumors or Low Grade Epithelial Cancers of the Ovary, Fallopian Tube and Primary Peritoneum

Using RECIST criteria, Objective Response evaluated every 2 months.

Age Continuous

Sex: Female, Male

United States

Region of Enrollment

John Kavanagh, MD / Professor

Complete Response

Partial Response

Stable Disease

Progressive Disease

Analysis was per protocol, only 9 of 12 eligible patients were evaluable for response.

Objective Response Rate Following Treatment With Letrozole

Overall Study

Sarcoma

Leiomyosarcoma

Neoplasms, Connective and Soft Tissue

Soft Tissue Sarcoma

Uterine Sarcoma

Letrozole 2.5 mg Tablet By Mouth Daily for 12 Weeks.

Patients receive no treatment. Follow up every 3 months.

2.5 mg Tablet By Mouth Daily for 12 Weeks.

Robert Coleman, MD

The goal of this clinical research study is learn if taking Femara (letrozole) after a hysterectomy (surgical removal of the uterus) for uterine leiomyosarcoma will delay or prevent the cancer from coming back.

Letrozole is an aromatase inhibitor. Aromatase is the enzyme that produces estrogen in post-menopausal women. By interfering with the production of estrogen triggered by aromatase, letrozole reduces the total amount of estrogen in the body. As a result, less estrogen can reach cancer cells, thus preventing their growth.

Before you can start treatment on this study, you will have "screening tests." These tests will help the doctor decide if you are eligible to take part in this study. These exams, tests, or procedures are part of regular cancer care and may be done even if you do not join the study. If you have had some of them recently, they may not need to be repeated. This will be up to your study doctor.

Your complete medical history will be recorded, and you will have a physical exam (including a pelvic exam). Your vital signs and blood pressure will be measured. Blood (about 2-3 teaspoons) will be drawn for routine tests. You will also have a blood test (1 teaspoon) to check your cholesterol. You will have an electrocardiogram (ECG -- a test that measures the electrical activity of the heart). You will also have a chest x-ray, and either a computed tomography (CT) scan or a magnetic resonance imaging (MRI) to check the status of the disease. Your doctors will test previously collected tumor tissue to learn if the estrogen receptor is positive or negative.

If you are found to be eligible to take part in this study, you will be randomly assigned (as in the toss of a coin) to 1 of 2 groups. Group 1 will receive letrozole by mouth once a day. Group 2 will receive no treatment. Both groups will be followed closely every 3 months. You will have an equal chance of being placed in either group.

If you are in Group 1, you will take letrozole by mouth every day for 12 weeks. Every 12 weeks is considered a study "cycle." You will only be given the amount of drug needed for 1 cycle of therapy at a time. You will keep a diary during the study that will list when and how much drug you took. This diary will be reviewed after each cycle of therapy by the research nurse or doctor and filed in your chart.

Every 12 weeks, all participants will have blood (about 3-4 teaspoons) drawn for routine tests. CT scan of the chest, abdomen (stomach area), and pelvis will be done every 24 weeks. In addition, all participants will have a physical exam (including a pelvic exam), and your vital signs and blood pressure will be measured.

You may remain on study for as long as you are benefitting. You will be taken off study if intolerable side effects occur.

Once you are off study, blood (about 2-3 teaspoons) will be drawn for routine tests and to measure your cholesterol level. You will have a physical exam (including a pelvic exam), and an MRI or CT scan.

This is an investigational study. Letrozole is approved by the FDA for treatment of some breast cancer patients after surgery. Its use in patients with leiomyosarcoma is experimental. Up to 80 patients will take part in this study. All will be enrolled at M. D. Anderson.

Letrozole Versus Observation in Patients With Newly Diagnosed Uterine Leiomyosarcoma

A Randomized Phase II Study of Letrozole Versus Observation in Patients With Newly Diagnosed Uterine Leiomyosarcoma

Number of participants progressed or death from study entry.

5 Participants was under observation and received no treatments

Letrozole 2.5 mg Tablet By Mouth Daily for 12 Weeks.

Letrozole: 2.5 mg Tablet By Mouth Daily for 12 Weeks.

Standard of Care

Standard of Care-Patients receive no treatment.

Total

Age, Categorical

Age, Continuous

Race (NIH/OMB)

Coleman,Robert,M.D. / Gyn Onc & Reproductive Medicine

1 out of 4 participants in the Letrozole arm progressed on study. 2 participants progressed in standard of care

Progression Free Survival (PFS)

letrozole 2.5 mg PO daily for 2-3 weeks prior to hysterectomy.

2.5 mg daily from the day of enrollment to the day before surgery, generally about 3 weeks

Lloyd H. Smith, MD, PhD

Some cases of endometrial cancer are dependent on estrogen for their growth. Letrozole blocks estrogen production in the body. The purpose of this study is to determine if the investigators can predict which patients might benefit from Letrozole treatment by studying the many different forms of the estrogen receptor molecule that exist within the cancer tissues. To participate in this study, the patients must be 40 years of age or older and have biopsy-proven endometrial carcinoma, either well differentiated or moderately differentiated forms. Also, to be eligible to participate in this study, the patients need to be healthy enough to have a hysterectomy. If the patients are less than age 60, they will need a blood test (FSH) to confirm that they have gone into menopause.

Letrozole as a Treatment of Endometrial Cancer

Predicting Aromatase Inhibitor Responsiveness in Endometrial Carcinoma

Changes in %Ki67 staining cells by immunoperoxidase of paraffin embedded, formalin fixed tissue

University of California, Davis

Adverse events for control arm not collected.

Letrozole 2.5 mg PO daily for 2-3 weeks prior to hysterectomy or re-biopsy.

Letrozole: 2.5 mg daily from the day of enrollment to the day before surgery (generally about 3 weeks) or to the day of repeat endometrial biopsy 9medical treatment arm).

Control

Grade 1 or 2 endometrial cancer treated 3 weeks before hysterectomy of repeat biopsy. Letrozole 2.5 mg PO daily.

Letrozole Arm

Subjects and controls selected to give groups similar in age and tumor grade. Four subjects excluded - wrong tumor type. One treatment arm completed but was excluded from analysis because of late completion.

Lloyd H. Smith MD, PhD

letrozole 2.5 mg PO daily for 2-3 weeks prior to hysterectomy.

Letrozole: 2.5 mg daily from the day of enrollment to the day before surgery, generally about 3 weeks

Subjects completing treatment who had confirmed histopathology compared to a non-randomized group of untreated control subjects. "Aromatase inhibitor responsiveness" was defined as a proportionate decline in %Ki67 staining of at least 70% between pre-treatment biopsy and hysterectomy 9or repeat biopsy).

Changes in Ki67 Expression After About 3 Weeks of Letrozole Treatment for Patients With Endometrial Cancer

Digestive System Diseases

Peritoneal Neoplasms

Abdominal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Peritoneal Diseases

Femara

Placebo capsule by mouth daily x 12 weeks

Placebo

Judith Wolf, MD

Primary Objective:

1. Evaluate the efficacy of letrozole to increase the duration of progression-free survival (defined as time to earliest occurrence of local or distant recurrence or clinically significant elevation in CA-125) when used as adjuvant treatment after completion of primary surgery and first line platinum containing chemotherapy in patients with optimally debulked (\< 1 cm residual disease) stage IIA-IIIC ovarian, fallopian tube, or primary peritoneal cancer.

Secondary Objective:

1. Observe the incidence of local and distant recurrences.

THE STUDY DRUG:

Letrozole is designed to block the enzyme that makes estrogen in post-menopausal women. By interfering with the production of estrogen made by the enzyme, letrozole decreases the total amount of estrogen in the body. As a result, less estrogen can reach cancer cells, which may prevent their growth.

SCREENING TESTS:

Before you can begin taking the study drug on this study, you will have "screening tests" to help the doctor decide if you are eligible to take part in this study. The following tests and procedures will be performed:

* Your complete medical history will be recorded.
* You will have a physical exam, including a pelvic exam and measurement of your vital signs (blood pressure, heart rate, temperature, and breathing rate).
* Blood (about 2-3 teaspoons) will be drawn for routine tests and to test for tumor markers.
* You will have a chest x-ray and a computed tomography (CT) scan or magnetic resonance imaging (MRI) scan to check the status of the disease.
* Your previously collected tumor tissue, if available, will be tested to learn if the estrogen receptor is positive or negative.
* You will be asked how well you are able to perform the normal activities of daily living (performance status evaluation).

STUDY GROUPS:

If you are found to be eligible to take part in this study, you will be randomly assigned (as in the flip of a coin) to 1 of 2 groups. Group 1 will take letrozole. Group 2 will take a placebo. A placebo is a substance that looks like the study drug but has no active ingredients. Neither the doctor nor you will know which group you will be in. However, if needed for your safety, the study staff and study doctor will be able to find out which group you are in.

STUDY DRUG ADMINISTRATION:

You will take letrozole or the placebo by mouth 1 time every day of each 12-week study "cycle". It should be taken around the same time every day and can be taken with or without food and/or water. You will be given the amount of study drug/placebo needed for 1 cycle of therapy at a time.

You will keep a drug "diary" during the study. In this diary you will list when and how much study drug/placebo you took. This diary will be reviewed after each cycle.

STUDY VISITS:

Within 4 weeks before your first dose of study drug/placebo, you will have a bone scan to test your bones and to watch for any signs of osteoporosis (weakened bones) that can be caused by decreased estrogen levels. You will be separately consented for this bone scan, which will describe the procedure and its risks in detail.

Every 12 weeks, the following tests and procedures will be performed:

* Blood (about 2-3 teaspoons) will be drawn for routine tests and to test for tumor markers.
* You will have a CT scan of the chest, abdomen, and pelvis to check the status of the disease.
* You will have a physical exam, including a pelvic exam and measurement of your vital signs and weight.
* You will have a performance status evaluation.
* You will be asked if you have experienced any side effects.

Every 6 months, you will have a chest x-ray.

Every year, you will have a bone scan to check for osteoporosis.

LENGTH OF STUDY:

You may remain on the study for as long as you are not experiencing intolerable side effects and the disease has not gotten worse. In that case, you will be taken off study. The total length of the study is five (5) years. At the end of the study, if you are still on active treatment, you and your doctor may or may not decide to continue treatment off-study.

END-OF-STUDY VISIT:

On the last day that you take the study drug/placebo, you will have an end-of-study visit. The following tests and procedures will be performed:

* Blood (about 2-3 teaspoons) will be drawn for routine tests and to test for tumor markers.
* You will have a physical exam, including a pelvic exam and measurement of your vital signs and weight.
* You will have an MRI scan or CT scan to check the status of the disease.
* You will have a performance status evaluation.
* You will be asked if you have experienced any side effects.

This is an investigational study. Letrozole is commercially available and FDA approved for the treatment of some types of breast cancer. Its use in patients with ovarian cancer is experimental. While you are on study, letrozole or the placebo will be provided at no cost to you.

Up to 50 patients will take part in this study. All will be enrolled at M. D. Anderson.

Femara (Letrozole) Versus Placebo for Patients With Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

A Phase II, Double-Blinded, Randomized Evaluation of Femara (Letrozole) Versus Placebo for Adjuvant Treatment After Completion of First-Line Chemotherapy for Patients With Optimally Debulked and Chemoresponsive Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

PFS defined as time to earliest occurrence of local or distant recurrence or clinically significant elevation in CA-125. Biochemical progression is defined as two serially rising serum values of CA-125 greater than or equal to two times the upper limits of normal (ULN \>35 U/ML) performed at least one week apart, regardless of CT scan results.

Novartis Pharmaceuticals

2.5 mg daily by mouth every day, at same time as Everolimus.

RAD001 (Everolimus)

Pamela T. Soliman, MD

The goal of this clinical research study is to learn if the combination of RAD001 (everolimus) and Femara (letrozole) can help to control recurrent or progressive endometrial cancer. The safety of this drug combination will also be studied.

The Study Drugs:

Everolimus is designed to stop cancer cells from multiplying. It may also stop the growth of new blood vessels that help tumor growth, which may cause the tumor cells to die.

Letrozole is designed to block chemical pathways that are necessary for tumor growth.

Study Drug Administration:

If you are found to be eligible to take part in this study, you will take 2 pills of everolimus by mouth 1 time every day. You should not open everolimus until you are about to take it because it absorbs moisture and is sensitive to light. You will also take 1 pill of letrozole by mouth 1 time every day. You should take letrozole at the same time as everolimus.

Everolimus should be taken the same time every day on an empty stomach (fasting state) or after no more than a light, fat-free meal. You should wait at least 6 hours after a eating a regular (not fat-free meal) before taking everolimus. You should not eat fatty foods for at least 1 hour after taking everolimus.

If you cannot swallow the tablets, the tablets should be dissolved in a glass of about 2 tablespoons of water just before being taken. The tablets should then be stirred gently (for a maximum of 7 minutes) until the tablets are dissolved. The contents should then be drunk. If you vomit after taking the study drug, you should not take another tablet that day. If you forgot to take the drug one day, you should not take an extra dose the next day but instead contact your doctor for advice.

You will be given a diary where you will record the pills you take each day. You must bring this diary to each visit.

While you are on study, you should avoid grapefruit, grapefruit juice, and other products containing grapefruit. There are also certain drugs you cannot take during this study. You should not take any drugs during the study without asking the study doctor first.

Study Visits:

Every 4 weeks, the following tests and procedures will be performed:

* You will have a physical exam, including measurement of your weight and vital signs (blood pressure, heart rate, breathing rate, and temperature).
* Your performance status will be recorded.
* Blood (about 2 tablespoons) will be drawn for routine tests, including checking your liver and kidneys and measuring the levels of sugar in your blood, and levels of fat in your blood.
* You will asked about any side effects you have experienced.
* If the disease is in the pelvis, you will have a pelvic exam.
* If the doctor thinks it is needed, blood (about 1 teaspoon) will be drawn for hepatitis testing.
* Your pills will be counted.

At Week 8, the following tests and procedures will be performed:

* You will have a physical exam, including a pelvic exam.
* You will have a CT and/or MRI scan of your chest, abdomen, and pelvis. Other areas will be scanned if the doctor thinks it is needed.
* Any tumors will be measured. The doctor will either feel the tumor or a CT, x-ray, and/or MRI will be used.
* If the disease is in your chest, you will have chest CT and/or MRI scan to check the status of the disease.
* You will asked about any side effects you have experienced.

After the Week 8 Visit, you will have the following tests and procedures. (If the disease has partially or completely responded to the study drugs, these tests will be done around Week 12. If the disease is stable, these tests will be done around Week 16.)

* You will have a physical exam.
* You will have a CT and/or MRI scan of your chest, abdomen, and pelvis. Other areas will be scanned if the doctor thinks it is needed.
* Any tumors will be measured. The doctor will either feel the tumor or a CT scan, x-ray, and/or MRI will be used.
* If the disease is in your chest, you will have a chest CT and/or MRI scan to check the status of the disease.

After the Week 12 or 16 visit, every 12 weeks, the following tests and procedures will be performed:

* You will have a pelvic exam.
* You will have a CT and/or MRI scan of your chest, abdomen, and pelvis. Other areas will be scanned if the doctor thinks it is needed.

I-f the disease is in your chest, you will have chest CT and/or MRI scan to check the status of the disease.

Length of Study:

You may continue receiving additional cycles of study treatment. You will be taken off study if you experience intolerable side effects, the disease gets worse, the disease completely responds, or the doctor thinks it is in your best interest.

End of Treatment Visit:

Within 4 weeks after the last dose of study drugs, you will have an end-of-treatment visit. At this visit, the following tests and procedures will be performed:

* You will have a physical exam, including measurement of your weight and vital signs.
* You will have a pelvic exam.
* Your performance status will be recorded.
* Blood (about 2 tablespoons) will be drawn for routine tests, including checking your liver and kidneys and measuring the levels of sugar in your blood, and levels of fat in your blood.
* You will have a CT and/or MRI scan of your chest, abdomen, and pelvis. Other areas will be scanned if the doctor thinks it is needed.
* If the disease is in your chest, you will have chest CT and/or MRI scan to check the status of the disease.
* Your pills will be counted and any unused study drug will be returned.

Long Term Follow-up:

After you are off study, you will be followed by your doctor on a regular basis. How often these visits occur are up to you and your doctor. The following tests and procedures will be performed:

* You will have a physical exam, including measurement of your weight and vital signs.
* You will have a pelvic exam.
* Your performance status will be recorded.
* You will be asked if you have experienced any intolerable side effects.
* You will have a CT and/or MRI scan of your chest, abdomen, and pelvis. Other areas will be scanned if the doctor thinks it is needed.
* If the disease is in your chest, you will have chest CT and/or MRI scan to check the status of the disease.

This is an investigational study. Everolimus is not FDA approved or commercially available. At this time, everolimus is only being used in research. Letrozole is FDA approved and commercially available for the treatment of breast cancer and ovarian cancer. The combination of everolimus and letrozole in this study for the treatment of endometrial cancer is also investigational. Up to 42 patients will take part in the multicenter study. Up to 42 will be enrolled at MD Anderson.

Letrozole and RAD001 With Advanced or Recurrent Endometrial Cancer

A Phase II Study of Letrozole and RAD001 (Everolimus) in Patients With Advanced or Recurrent Endometrial Cancer

Objective response or stable disease rate monitored as patients accrue and are evaluated following the example of Thall and Simon. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR

PFS is the time from first dose of study treatment until the first date of either objective disease progression or death due to any cause. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 30% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. Median PFS was estimated using the Kaplan-Meier method.

OS is defined as the interval from first dose of study treatment to the date of death, irrespective of the cause of death; subjects still alive will be censored at the date of the last contact

Toxicity was assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events (version 3.0).

RAD001 10 mg oral tablet daily + Letrozole 2.5 oral tablet daily for 28 days

RAD001 + Letrozole

Ethnicity (NIH/OMB)

All participants were included in the analysis

Dr. Pamela Soliman,Professor, Gyn Onc & Reproductive Med

Complete Response (CR)

Partial Response (PR)

Number of Participants With Objective Response Rate

Median Progression Free Survival (PFS)

Median Overall Survival (OS)

Number of Participants With Disease Progression

Number of Participants With Adverse Events (All Grades)

Skin and Connective Tissue Diseases

Breast Neoplasms

Breast Diseases

Skin Diseases

Anastrozole

Pazopanib

Hope Rugo, M.D.

The purpose of this study is to evaluate the clinical benefit rate at 12 weeks from the addition of pazopanib to a non-steroidal aromatase inhibitor (NSAI) (letrozole or anastrozole) in patients with hormone receptor positive advanced breast cancer progressing on the same NSAI hormone therapy.

In this trial, the investigators propose to evaluate the role of VEGFR blockade with the tyrosine kinase inhibitor pazopanib in combination with nonsteroidal aromatase inhibitors (NSAI) in patients who are progressing or have relapsed on the same NSAI hormone therapy given for advanced or early stage breast cancer. If this trial demonstrates clinical benefit, this all oral combination could be tested in both the neoadjuvant and metastatic settings in a randomized phase II design.

In order to investigate potential factors predicting response or resistance to pazopanib and NSAIs, several translational studies have been incorporated into this trial.

The prognostic value of circulating tumor cells (CTC) has been demonstrated in several studies in breast cancer, especially in advanced stage \[35-38\]. At University of California, San Francisco (UCSF) in the laboratory of Dr. John Park, the investigators have demonstrated expertise in the measurement of CTC in patients with advanced stage breast cancer by IC/FC assay. CTC are first enriched with immunomagnetic beads coated with EpCAM, then EpCAM+, CD45-, nucleic acid+ cells are detected by flow cytometry. This technique is highly sensitive and reproducable, and allows sorting of cells for molecular analysis as well as analysis of cell surface markers\[39\]. In this trial, the investigators will collect patient's peripheral blood samples every 4 weeks while on treatment and follow any reduction of CTC.

The mechanisms of hormonal resistance includes intrinsic and acquired pathways: decreased ER expression accounts for intrinsic resistance and the increased receptor tyrosine kinase pathway relates to acquired resistance \[40-42\]. The investigators plan to analyze the mutation of PI3K/Akt and deletion of PTEN by sequencing in CTC (depending on numbers of cells, which in turn determines feasibility), in order to make a preliminary assessment of potential markers of response to pazopanib.

The tumor microenvironment plays an important role in cancer development and progression. Clinical studies have revealed that the increased T regulatory cells (Treg), high ratios of CD4/CD8 T lymphocytes, and extra follicular B cells in primary tumors correlated with worse overall survival \[43-45\]. Recently, studies from preclinical models have shown that tumor associated macrophages (TAM) can promote pulmonary metastases in breast cancer animal models, and in both the preclinical and clinical settings are associated with worse clinical outcome \[46-48\]. TGFβ has been linked to hormonal resistance in breast cancer. The activation of TGFβ leads to increased regulatory CD4+ T cells and decreased cytotoxic CD8+ T cells in the tumor microenvironment \[49\]. A recent study in non-small cell lung cancer suggests that baseline and post-treatment levels of cytokines, particularly IL-4 and IL-12 correlated with response to pazopanib\[50\]. In this study, the investigators will collect patient's serum to monitor the level of cytokines at baseline and during treatment, the investigators will compare the change of cytokine level with pazopanib in each patient, and also compare between responders and non-responders. This information may help us to identify biomarkers that would predict response to antiangiogenic therapy and to identify possible mechanisms of resistance.

Reversing Hormone Resistance in Advanced Breast Cancer With Pazopanib

For the purpose of this study, participants who obtained a complete response (CR), partial response (PR), or stable disease (SD) at 12 weeks per Response Evaluation Criteria in Solid Tumors (RECIST) guidelines version 1.1 were defined as having a clinical benefit from the treatment. An overall response rate of 20% was considered to be clinically meaningful. All participants who take at least two weeks of study drug and the non-steroidal aromatase inhibitor were evaluated for toxicity and efficacy

Evaluate progression free survival with ongoing evaluations at 12 week intervals until progression or up to 2 years, whichever is first.

All patients who take at least two weeks of study drug and the non-steroidal aromatase inhibitor will be evaluable for treatment-related toxicity by ongoing evaluations at 4 week intervals until progression or up to 2 years, whichever is first.

GlaxoSmithKline

Hope Rugo, MD

Clinical Professor

Non-randomized, open label

Pazopanib: Oral, 800mg tablet daily per cycle

Pazopanib in Combination With a NSAI

40-49 years

50-59 years

60-69 years

70-79 years

Age, Customized

Dr. Hope Rugo, MD

Twenty-eight patients met the 2 weeks of treatment minimum needed to be considered evaluable for this endpoint.

Number of Participants With Clinical Benefit (CB)

Progression Free Survival

Number of Participants Experiencing Any Treatment-related Adverse Events (AE)

Women treated for breast cancer who will be starting Arimidex or Femara

Pamela Taxel, MD

Aromatase Inhibitors (AI) are effective for secondary prevention of breast cancer and may soon replace tamoxifen as first-line therapy in the treatment of hormone-sensitive breast cancer. However, because these medications produce a marked reduction in serum estrogen levels, this is likely to result in an increased rate of bone loss and risk of developing osteoporosis and fractures in postmenopausal women treated with these agents. Indeed, substantial bone loss has been reported in several large clinical trials of AIs. Osteoporosis drugs are available that could prevent this loss, but they have frequent side effects and are expensive. Thus, treating all women receiving AIs might not be the most appropriate and cost-effective approach. A better approach might be to select women at highest risk of bone loss and only treat them with antiresorptive agents.

The proposed pilot study will evaluate women who receive anastrozole or letrozole therapy, are receiving adequate amounts of calcium and vitamin D and have baseline normal or moderately low bone mass in order to determine if early changes in bone turnover markers correlate with bone loss at one year. If data from this pilot protocol support our hypothesis, then we would propose a larger trial to confirm it. The ultimate aim is to predict which women are at higher risk of bone loss and therefore treat them earlier with bone-sparing agents, while those with lower risk could be monitored on conservative therapy.

Anastrozole and Letrozole

Effect Of Anastrozole And Letrozole On Bone Turnover Markers And Bone Mineral Density In Postmenopausal Women With Primary Breast Cancer: A Pilot Study

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Phase II, Single-Arm Study of RAD001 (Everolimus), Letrozole, and Metformin in Patients With Advanced or Recurrent Endometrial Carcinoma	NCT01797523	Endometrial Can...	Metformin Letrozole Everolimus	18 Years -	M.D. Anderson Cancer Center
Letrozole in Patients With Ovarian Tumors	NCT00505661	Ovarian Cancer Fallopian Tube ... Peritoneal Canc...	Letrozole	18 Years -	M.D. Anderson Cancer Center
Letrozole Versus Observation in Patients With Newly Diagnosed Uterine Leiomyosarcoma	NCT00414076	Leiomyosarcoma Uterine Neoplas...	Letrozole	18 Years -	M.D. Anderson Cancer Center
Letrozole as a Treatment of Endometrial Cancer	NCT00997373	Endometrial Car...	Letrozole	40 Years -	University of California, Davis
Femara (Letrozole) Versus Placebo for Patients With Ovarian, Fallopian Tube, or Primary Peritoneal Cancer	NCT00634894	Ovarian Cancer Fallopian Tube ... Peritoneal Canc...	Femara Placebo	-	M.D. Anderson Cancer Center
Letrozole and RAD001 With Advanced or Recurrent Endometrial Cancer	NCT01068249	Endometrial Can...	Letrozole RAD001 (Everoli...	18 Years -	M.D. Anderson Cancer Center
Letrozole in Patients With Ovarian Tumors	NCT00505661	Ovarian Cancer Fallopian Tube ... Peritoneal Canc...	Letrozole	18 Years -	M.D. Anderson Cancer Center
Reversing Hormone Resistance in Advanced Breast Cancer With Pazopanib	NCT01466972	Breast Cancer Breast Neoplasm	Pazopanib	18 Years -	University of California, San Francisco
Reversing Hormone Resistance in Advanced Breast Cancer With Pazopanib	NCT01466972	Breast Cancer Breast Neoplasm	Pazopanib	18 Years -	University of California, San Francisco
Reversing Hormone Resistance in Advanced Breast Cancer With Pazopanib	NCT01466972	Breast Cancer Breast Neoplasm	Pazopanib	18 Years -	University of California, San Francisco
Letrozole and RAD001 With Advanced or Recurrent Endometrial Cancer	NCT01068249	Endometrial Can...	Letrozole RAD001 (Everoli...	18 Years -	M.D. Anderson Cancer Center
Anastrozole and Letrozole	NCT00762294	Breast Cancer		40 Years -	UConn Health

Spots Global Cancer Trial Database for femara

Every month we try and update this database with for femara cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for femara

Every month we try and update this database with for femara cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for femara cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.