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

Vorinostat

Histone Deacetylase Inhibitors

Anti-Bacterial Agents

Antibiotics, Antitubercular

Clotrimazole

Miconazole

Antifungal Agents

Escalation Phase: Vorinostat starting dose 100 mg by mouth on Days 7 - 28 of Cycle 1; For all other cycles, dose of 100 mg Days 1-28.

Expansion Phase starting dose: MTD from Escalation Phase.

Escalation Phase: Sirolimus starting dose1 mg by mouth on Days 1 - 28.

Expansion Phase starting dose: MTD from Escalation Phase.

Escalation and Expansion Phase: Vorinostat dose 300 mg by mouth on Days 7 - 28. Rest of cycles: 300 mg by mouth on Days 1 - 28.

Escalation Phase: Everolimus starting dose 5 mg by mouth on Days 1 - 28.

Expansion Phase: MTD from Escalation Phase.

Escalation and Expansion Phase: Vorinostat dose 300 mg by mouth on Days 7 - 28. Rest of cycles: 300 mg by mouth on Days 1 - 28.

Escalation Phase: Temsirolimus starting dose 12.5 mg by vein on Days 1, 8, 15, 22.

Expansion Phase: MTD from Escalation Phase.

Escalation Phase: Sirolimus starting dose1 mg by mouth on Days 1 - 28.

Expansion Phase starting dose: MTD from Escalation Phase.

Arm A - Escalation Phase: Vorinostat starting dose 100 mg by mouth on Days 7 - 28 of Cycle 1; For all other cycles, dose of 100 mg Days 1-28.

Expansion Phase starting dose: MTD from Escalation Phase.

Arm B + Arm C - Escalation and Expansion Phase: Vorinostat dose 300 mg by mouth on Days 7 - 28. Rest of cycles: 300 mg by mouth on Days 1 - 28.

Escalation Phase: Everolimus starting dose 5 mg by mouth on Days 1 - 28.

Expansion Phase: MTD from Escalation Phase.

Escalation Phase: Temsirolimus starting dose 12.5 mg by vein on Days 1, 8, 15, 22.

Expansion Phase: MTD from Escalation Phase.

Filip Janku, MD, PHD

The goal of this clinical research study is to find the highest tolerable dose of the combination vorinostat given in combination with either sirolimus, everolimus or temsirolimus that can be given to patients with advanced cancer. The safety of this drug combination will also be studied.

The Study Drugs:

Vorinostat is designed to prevent or slow down the growth of cancer cells by blocking proteins.

Everolimus is designed to stop cells from dividing. This may stop or slow the growth or spread of cancer cells.

Temsirolimus is designed to block a protein called mTOR (a protein that is thought to cause cancer cells to grow) inside the cancer cell. This may interfere with the growth or spread of cancer cells or possibly kill them.

Sirolimus is designed to block a protein called mTOR inside the cancer cell. This may interfere with the growth or spread of cancer cells or possibly kill the cancer cells.

This is an investigational study. Sirolimus is FDA approved and commercially available as an anti-rejection drug for kidney transplant recipients. Everolimus is FDA-approved and commercially available for the treatment of pancreatic neuroendocrine tumor, subependymal giant cell astrocytoma, and renal cell carcinoma. Temsirolimus is FDA approved and commercially available for the treatment of renal cell carcinoma. Vorinostat is FDA approved and commercially available for the treatment of cutaneous T-cell lymphoma. The combination of these drugs is investigational.

Up to 249 patients will take part in this study. All will be enrolled at MD Anderson.

Study Drug Groups:

If you are found to be eligible to take part in this study, you will be assigned to a dose level of vorinostat and either sirolimus, everolimus, or temsirolimus based on when you joined this study. Up to 9 dose levels of sirolimus and vorinostat will be tested. Up to 3 dose levels of everolimus and vorinostat will be tested. Up to 3 dose levels of temsirolimus and vorinostat will be tested. Three (3) to 9 participants will be enrolled at each dose level. The first group of participants will receive the lowest dose level of the study drug combination. Each new group will receive a higher dose than the group before it, if no intolerable side effects were seen. This will continue until the highest tolerable dose of the combination vorinostat and sirolimus, everolimus, or temsirolimus is found.

Once the highest tolerated dose of the combinations are found, up to 14 participants with the tumor type that is most likely to respond to the study drug combinations will receive the study drugs at that dose level.

Study Drug Administration:

Each study "cycle" is 28 days.

There are 3 arms in this study, Arm A, Arm B, and Arm C. You will be assigned to an arm depending on when you enroll in the study and what your doctor thinks you will benefit from. You will take vorinostat either with sirolimus (Arm A), with everolimus (Arm B), or with temsirolimus (Arm C).

Everyday, you will take sirolimus by mouth 1 time a day. You should take it at about the same time each day with food and a cup (8 ounces) of water.

If you are in Arm A, on Day 7 of Cycle 1, you will start taking vorinostat by mouth 1 time a day. You should take it at about the same time each day with food and a cup (8 ounces) of water.

If your are in Arm B, you will take everolimus by mouth at the same time every day with or without food, swallowed whole with a glass (8 ounces) of water. Do not chew, break, or crush everolimus.

If you are in Arm C, you will receive temsirolimus by vein over 30-60 minutes on Days 1, 8, 15, and 22 of each cycle. You will be given standard drugs to help decrease the risk of side effects. You may ask the study staff for information about how the drugs are given and their risks.

Study Visits:

At every study visit, you will be asked about any current health conditions you have, drugs you may be taking, and if you have had any side effects.

About Days 8 and 22 of Cycle 1:

* You will have a physical exam.
* Blood (about 2 teaspoons) will be drawn for routine tests.

If you are enrolled in Arm B and have Hodgkin lymphoma, on Days 8 and 28 of Cycle 1:

* You will have a needle tumor biopsy. This biopsy will be used for DNA testing and to check for a response to the study drugs, as described above in the "Screening Tests" section.
* Blood (about 1 tablespoon) will be drawn for biomarker testing.

About Day 15 of Cycle 1, blood (about 2 teaspoons) will be drawn for routine tests.

About Day 22 of Cycles 2 and beyond:

You will have a physical exam. Blood (about 2 teaspoons) will be drawn for routine tests.

Every 4 weeks, you will have a blood (about 1 teaspoon) drawn or urine collected for a pregnancy test if you are able to become pregnant.

Every 8 weeks, you will have an x-ray, CT scan, MRI, and/or PET/CT to check the status of the disease. If the study doctor thinks it is needed, they will be performed more often.

If you are enrolled in Arm B and have Hodgkin lymphoma, at any point that the disease appears to get worse:

* You will have a needle tumor biopsy. This biopsy will be used for DNA testing and to check for a response to the study drugs, as described above in the "Screening Tests" section.
* Blood (about 1 tablespoon) will be drawn for biomarker testing.

Length of Study:

You may continue taking the study drugs for as long as you are benefitting. You will be taken off study if you experience intolerable side effects, the study doctor thinks it is in your best interest, or the disease gets worse.

Sirolimus or Everolimus or Temsirolimus and Vorinostat in Advanced Cancer

A Phase I Trial of Sirolimus or Everolimus or Temsirolimus (mTOR Inhibitor) and Vorinostat (Histone Deacetylase Inhibitor) in Patients With Advanced Cancer

Maximum tolerated dose (MTD) defined by dose-limiting toxicities (DLTs) that 1) occur during the first four weeks of therapy, 2) are related to the study medications (attributions: possible, probable, and likely) and 3) fulfill one of the following criteria (as graded by the NCI Common Terminology Criteria for Adverse Events). MTD is defined as highest dose level in which 6 patients have been treated with less than 2 DLTs.

Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD.

Progressive Disease (PD): at least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.

Stable Disease (SD): neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started.

Digestive System Diseases

Rare Diseases

Liver Neoplasms

Neuroendocrine Tumors

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Liver Diseases

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms, Nerve Tissue

Neuroendocrine Tumor

Neuroepithelioma

Hematinics

Liver Extracts

Each cycle is 28 days. Target dose of TheraSphere is fixed at 120 Gy to entire tumor bearing portion of liver given at a single session on Cycle 1 Day 15. The dose of everolimus will be escalated in 2 sequential cohorts of 6 TheraSphere-treated patients each. Starting dose of everolimus is 5 mg by mouth daily for cycles 1 and 2. Patients will receive standard dose of Everolimus at 10 mg PO daily starting cycle 3 day 1.

Once DLT is defined or dose level 2 has been completed, a dose expansion cohort of 10 patients with advanced low to intermediate grade neuroendocrine tumor will be enrolled.

At least 1 time a week by phone or at the clinic for up to 30 days after last everolimus dose, study staff will follow up. Patient asked about any side effects they may have had.

TheraSphere glass microspheres containing Y-90 injected into catheter, and will deliver 120 Gy to entire tumor bearing portion of the liver given at a single session on Cycle 1 Day 15.

TheraSphere

Starting dose: is 5 mg by mouth daily for cycles 1 and 2. Patients will receive standard dose of Everolimus at 10 mg by mouth daily starting cycle 3 day 1.

Dose Expansion Cohort Starting Dose: Maximum tolerated dose from dose escalation cohort.

At least 1 time a week by phone or at the clinic for up to 30 days after last everolimus dose, study staff will follow up. Patient asked about any side effects they may have had. The call should last about 10-15 minutes.

Phone Call

Nageshwara V. Dasari, MBBS

The goal of this clinical research study is to find the highest tolerable dose of the combination of everolimus with TheraSphere that can be given to patients with advanced NETs that have spread to the liver. The safety of everolimus and TheraSphere will also be studied.

Everolimus is designed to block a protein inside the cancer cells, which is also involved in cancer growth.

TheraSphere is a medical device containing a radioactive material called yttrium-90 (Y-90). Tiny glass beads called microspheres are filled with Y-90 and then injected through an artery directly into the liver. This allows a large dose of radiation to be given directly to the tumor, which may lower the risk of side effects from the radiation to other parts of the body and/or to healthy liver tissue. The radiation from TheraSphere stays in the body and begins to lose its effect within 12 days. The glass microspheres will stay in the body from that point on. The radiation will eventually decay (go away). By the time a participant leaves the hospital, the amount of radiation outside of the body will be low enough to not be a threat to others.

Study Groups:

If patient is are found to be eligible to take part in this study, they will be assigned to a dose level of everolimus based on when they joined this study. Up to 3 dose levels of everolimus will be tested. Up to 6 participants will be enrolled at each dose level. The first group of participants will receive the low dose level. Each new group will receive a higher dose than the group before it, if no intolerable side effects were seen. If intolerable side effects are seen, the dose may be lowered. This will continue until the highest tolerable dose of everolimus is found. After that, 10 additional participants will be enrolled at the highest tolerable dose that was found.

All participants will receive the same dose level of TheraSphere.

Study Drug Administration:

Each study cycle is 28 days.

On Day 1 of Cycle 1, 2 weeks before the TheraSphere procedure, patient will start taking everolimus.

Patient will take 1-2 tablets of everolimus by mouth 1 time every day. Patient will take the everolimus tablets with a glass of water in the morning at the same time every day. The tablets should be swallowed whole and not chewed or crushed. The tablets may be taken either always with or always without food.

If patient vomits after taking their dose, they should not take another tablet that day. It is very important that patients take the tablets given to them just as the study doctor tells them and that they do not miss any tablets. If patient does forget to take it one day, they should not take any extra doses the next day. Instead, patient should contact their doctor and ask for advice.

On the days of patient's study visits, they should take their dose of everolimus at the clinic, not at home.

TheraSphere Administration:

About 2 weeks before the TheraSphere procedure, patient will have an angiogram. An angiogram is an imaging test that uses contrast dye to help the doctor look at the body's blood vessels. Patient will be given drugs by vein in their arm or hand to help them relax, but patient will stay awake during the procedure. An area in patient's groin will be numbed with anesthetic.

During the procedure, the doctor will insert a catheter into a blood vessel in patient's groin that leads to their liver. Dye will be injected into the catheter, and a series of x-rays will be taken that will allow the doctor to see the blood vessels in patient's liver. At the end of the procedure, the catheter will be removed from patient's groin area. The x-rays taken will be looked at by patient's doctor to plan for their TheraSphere procedure. The angiogram procedure should take about 1½ to 3 hours.

On Day 15 of Cycle 1, patient will receive TheraSphere. Before the procedure, patient will be given drugs by vein in their arm or hand to help them relax, but patient will stay awake during the procedure. An area in patient's groin will be numbed with anesthetic. Patient may ask the study staff for information about how the anesthesia drugs are given and their risks.

The doctor will insert a catheter into a blood vessel in patient's groin that leads to their liver. Based on the planning from patient's angiogram procedure, the doctor will guide the catheter to the target blood vessel. Once the catheter is in the proper blood vessel, the TheraSphere microspheres containing Y-90 will be injected into the catheter to reach the tumor in the liver. After the TheraSphere microspheres are injected, the catheter will be removed from patient's groin. The entire procedure will take about 1½ to 3 hours.

After receiving the TheraSphere microspheres, patient will stay in the recovery area for several hours so that the staff can check patient for possible side effects. If patient has any serious side effects, they may be admitted to the hospital to be checked on and for treatment, if needed.

Study Visits:

Before all visits, patient must fast starting at midnight the night before.

On Day 1 of Cycle 1, if the tests have not been done in the last 5 days:

* Patient will have a physical exam, including measurement of their weight and vital signs.
* Patient will be asked about any symptoms they may have had and any drugs they may be taking.
* Patient's performance status will be recorded.
* Blood (about 4 tablespoons) will be drawn for routine tests and tumor marker testing.
* Urine will be collected for routine tests.
* If patient's doctor thinks it is needed, blood (about 2 teaspoons) will be drawn to check for hepatitis B and/or C.

On Day 14 or 15 of Cycle 1:

* Patient will have a physical exam, including measurement of their weight and vital signs.
* Patient will be asked about any side effects they may have had.
* Patient's performance status will be recorded.
* Blood (about 3 tablespoons) will be drawn for routine tests.

On Day 1 of Cycles 2 and beyond:

* Patient will have a physical exam, including measurement of their weight and vital signs.
* Patient will be asked about any side effects they may have had and any drugs they may be taking.
* Patient's performance status will be recorded.
* Blood (about 1 tablespoon) will be drawn for routine tests.

On Day 1 of Cycles 2 and 3 and every 3-6 weeks after that, blood (about 2 teaspoons) will be drawn to check for hepatitis B and/or C if the doctor thinks it is needed.

On Day 1 of Cycles 2, 4, and every 3 cycles after that, blood (about 2 tablespoons) will be drawn for tumor marker testing and additional routine tests.

On Day 1 of Cycles 4 and beyond, urine will be collected for routine tests.

On Day 1 of Cycle 4 and every 3 cycles after that, patient will have a CT scan, MRI, and/or x-ray to check the status of the disease.

Length of Dosing:

Patient will receive TheraSphere on Day 15 of Cycle 1 and they may continue taking everolimus for up to 12 cycles, as long as the doctor thinks it is in patient's best interest. Patient will no longer be able to take everolimus if the disease gets worse, if intolerable side effects occur, or if they are unable to follow study directions.

Patient's participation on the study will be over once they have completed the follow-up.

End-of-Dosing Visit:

Within 1 week after patient stops taking the study drug, the following tests and procedures will be performed. Patient must fast starting at midnight the night before this visit.

* Patient will have a physical exam, including measurement of their weight and vital signs.
* Patient will be asked about any side effects they may have had.
* Patient's performance status will be recorded.
* Blood (about 3 tablespoons) will be drawn for routine tests and tumor marker testing. This blood draw will include a pregnancy test if patient can become pregnant.
* Urine will be collected for routine tests.
* Patient will have a CT scan, MRI, and/or x-ray to check the status of the disease.

Follow-up:

At least 1 time a week by phone or at the clinic for up to 30 days after patient's last everolimus dose, the study staff will follow up with patient. Patient will be asked about any side effects they may have had. The call should last about 10-15 minutes.

If patient left the study because of a side effect, they will continue to be contacted by the study staff until the side effect has gone away or become stable.

This is an investigational study. Everolimus is commercially available and FDA approved to treat advanced pancreatic NETs and other types of cancer. The combination of everolimus and TheraSphere in this study is investigational.

TheraSphere is commercially available and FDA approved as a radiation treatment for liver cancer. The use of TheraSphere in this study is investigational.

Up to 22 participants will be enrolled in this study. All will take part at MD Anderson.

Phase 1 TheraSphere + Everolimus With Neuroendocrine Tumors (NETs) + Liver Only or Liver Dominant Disease

Phase I Study of TheraSphere and Everolimus Among Patients With Neuroendocrine Tumors and Liver Only or Liver Dominant Disease

Dose limiting toxicity (DLT) defined as any toxicity occurring during the first 56 days of therapy with definite, possible or probable attribution to TheraSphere and/or Everolimus and meets CTCAE version 4.0 criteria.

BTG International Inc.

Novartis Pharmaceuticals

Adenocarcinoma

Esophageal Neoplasms

Head and Neck Neoplasms

Esophageal Diseases

Esophageal Cancer

Dose Escalation: Everolimus at a dose of 10 mg by mouth daily with dose escalation of LDE 225 from 200 mg - 800mg by mouth daily. Study cycle is 28 days.

Dose Expansion: Everolimus at a dose of 10 mg by mouth daily. LDE 225 at MTD from Dose Escalation. Study cycle is 28 days.

Induction and Dose Expansion Phase: 10 mg by mouth daily in a 28 day cycle.

Induction Phase Starting Dose: 400 mg by mouth daily in a 28 day cycle.

Expansion Phase Starting Dose: Maximum tolerated dose from Induction Phase.

LDE 225

Jaffer Ajani, MD

The goal of this clinical research study is to find the highest tolerable dose of LDE225 that can be given in combination with everolimus to patients with esophageal or GEJ cancer. The safety of the drug combination will also be studied.

Study Groups:

If participant is found to be eligible to take part in this study, participant will be assigned to a combination dose level of the study drugs based on when participant joins this study. Up to 6 participants will be enrolled at each dose level. The first group of participants will receive the lowest dose level of LDE225. Each new group will receive a higher dose than the group before it, if no intolerable side effects were seen. All participants will receive the same dose level of everolimus. This will continue until the highest tolerable combination dose of LDE225 and everolimus is found. Up to 24 participants will be enrolled in this part of the study.

Once the highest tolerable dose of the combination of LDE225 and everolimus is found, up to 18 participants will receive the combination dose level that was found to be well tolerated in the earlier part of the study.

Study Drug Administration:

Every study cycle is 28 days.

Participant will take up to 4 capsules or tablets of LDE225 by mouth 1 time every day. Participant's doctor will tell participant how many capsules/tablets participant will need to take. Participant should take the study drug each time with a glass of water (about 8 ounces total) at the same time every day. Participant should swallow the study drug whole, one capsule/tablet every 2 minutes, without chewing or opening the study drug. Participant should eat a light breakfast (such as toast and jam) at least 2 hours before taking the study drug, then participant should not eat or drink anything for at least 1 hour after the dose.

Participant will take up to 2 tablets of everolimus by mouth 1 time every day with the LDE225 capsules without food. Participant will take the tablets each time with a glass of water at the same time every day. The tablets should be swallowed whole and not chewed or crushed.

If participant cannot swallow the everolimus tablets, the tablets should be dissolved in water just before taking them. Add about 2 tablespoons of water into a glass. The tablets should then be added and stirred gently until the tablets are dissolved. This mixture should then be drunk. Afterwards, the glass should be rinsed with an additional 2 tablespoons of water and drunk. Participant's doctor will discuss this with participant.

If participant vomits after taking participant's dose of study drugs, participant should not take another dose that day.

It is very important that participant takes the study drugs given to participant just as the study doctor tells participant and that participant does not miss any dose. If participant forgets to take a dose of LDE225, participant should take it as soon as participant remembers (within 6 hours of the missed dose). If more than 6 hours have passed, participant should skip that dose and take participant's next dose the next day as planned. If participant forgets to take a dose of everolimus, participant should skip that dose and take participant's next dose the next day as planned.

If participant has a study visit that day, participant should take participant's dose of study drugs at the clinic.

Participant will need to store LDE225 in participant's refrigerator at all times. Everolimus can be stored at room temperature. Participant should not share participant's supply of LDE225 and everolimus with anyone. Participant will keep a study drug diary to help participant keep track of participant's study drug doses. If participant misses or delays a dose, participant should write it down in the diary. Participant should bring the diary to every study visit.

At the end of each cycle and when participant stops taking part in the study, participant will return any leftover study drugs to the study nurse.

Study Visits:

On Day 1 of every cycle:

* Participant will have a physical exam.
* Blood (about 2 teaspoons) will be drawn for routine tests.
* If participant can become pregnant, blood (about 1 teaspoon) or urine will be collected for a pregnancy test.

Every week during Cycle 1 only, the study staff will call and ask participant how participant is doing.

On Day 1 of Cycle 2 and every 2 cycles after that, participant will have an EKG.

On Day 1 of Cycle 3 and every 2 cycles after that, participant will have a CT scan or MRI of the chest, abdomen, and pelvis to check the status of the disease.

If the doctor thinks it is needed, extra blood may be drawn to follow up on any side effects.

Length of Study:

Participant may continue taking the study drugs for as long as the doctor thinks it is in participant's best interest. Participant will no longer be able to take the study drugs if the disease gets worse, if intolerable side effects occur, or if participant is unable to follow study directions.

Participation on the study will be over after the follow-up visit (described below).

End-of-Study Visit:

Within 14 days after participant's last dose of study drugs:

* Participant will have a physical exam.
* Blood (about 2 tablespoons) will be drawn for routine tests, to check the cholesterol levels in participant's blood, and to check how well participant's blood clots. Participant will need to fast for at least 8 hours before this blood draw.
* Participant will have an EKG.
* Participant will have a CT scan or MRI of the chest, abdomen, and pelvis to check the status of the disease, if the doctor thinks it is needed.
* If participant can become pregnant, blood (about 1 teaspoon) or urine will be collected for a pregnancy test.

Follow-Up Visit:

At 30 days after the end-of-study visit:

* Participant will have a physical exam.
* Blood (about 2 tablespoons) will be drawn for routine tests.
* Participant will have an EKG.
* If participant can become pregnant, blood (about 1 teaspoon) or urine will be collected for a pregnancy test.

About 3 months after the follow-up visit, participant will be contacted by the study staff by telephone and/or seen in the clinic. Participant will be asked about any drugs participant may be taking and about participant's general health. If participant is called, the call will take about 5-10 minutes.

This is an investigational study. LDE225 is not FDA approved or commercially available. Everolimus is FDA approved and commercially available to treat kidney, breast, and pancreatic cancers. The combination of LDE225 and everolimus to treat esophageal or GEJ cancer is investigational.

The study doctor can explain how the study drugs are designed to work.

Up to 42 participants will be enrolled in this study. All will take part at MD Anderson.

LDE225 + Everolimus in Advanced Gastroesophageal Adenocarcinoma

A Phase I Study of LDE225 in Combination With Everolimus in Patients With Advanced Gastroesophageal Adenocarcinoma

Maximum tolerated dose (MTD) defined as highest dose level for the combination therapy with no more than 1 out of 6 patients experiencing dose limiting toxicity (DLT). DLT defined as an adverse event (AE) or abnormal laboratory value assessed as at least possibly related to the study medication, occurs ≤56 days following the first dose of LDE225 (DLT assessment period).

A Bayesian method by Thall, Simon, and Estey \[37\] used for safety monitoring, starting from the 5th patient. The monitoring rule for toxicity is Pr (P(Tox) \> 0.25 \| data) \> 0.80, where P(Tox) is the proportion of patients that experience DLT and it has a prior distribution of beta (0.5, 1.5).

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
Sirolimus or Everolimus or Temsirolimus and Vorinostat in Advanced Cancer	NCT01087554	Advanced Cancer	Sirolimus Vorinostat Everolimus Temsirolimus	-	M.D. Anderson Cancer Center
Phase 1 TheraSphere + Everolimus With Neuroendocrine Tumors (NETs) + Liver Only or Liver Dominant Disease	NCT01864070	Liver Cancer	TheraSphere Everolimus Phone Call	18 Years -	M.D. Anderson Cancer Center
Sirolimus or Everolimus or Temsirolimus and Vorinostat in Advanced Cancer	NCT01087554	Advanced Cancer	Sirolimus Vorinostat Everolimus Temsirolimus	-	M.D. Anderson Cancer Center
LDE225 + Everolimus in Advanced Gastroesophageal Adenocarcinoma	NCT02138929	Esophageal Canc...	Everolimus LDE 225	18 Years -	M.D. Anderson Cancer Center
Phase 1 TheraSphere + Everolimus With Neuroendocrine Tumors (NETs) + Liver Only or Liver Dominant Disease	NCT01864070	Liver Cancer	TheraSphere Everolimus Phone Call	18 Years -	M.D. Anderson Cancer Center
LDE225 + Everolimus in Advanced Gastroesophageal Adenocarcinoma	NCT02138929	Esophageal Canc...	Everolimus LDE 225	18 Years -	M.D. Anderson Cancer Center

Spots Global Cancer Trial Database for zortress

Every month we try and update this database with for zortress 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 zortress

Every month we try and update this database with for zortress 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 zortress 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.