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

Information source: M.D. Anderson Cancer Center
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Endometrial Cancer

Intervention: Metformin (Drug); Letrozole (Drug); Everolimus (Drug)

Phase: Phase 2

Status: Recruiting

Sponsored by: M.D. Anderson Cancer Center

Official(s) and/or principal investigator(s):
Pamela Soliman, MD, Principal Investigator, Affiliation: M.D. Anderson Cancer Center

Overall contact:
Pamela Soliman, MD, Phone: 713-745-2352

Summary

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.

Clinical Details

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

Study design: Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: Clinical Benefit Rate (CBR)

Secondary outcome: Progression-Free Survival (PFS)

Detailed description: Study Drug Administration: If participant is found to be eligible to take part in this study and they are not already taking metformin, they will take metformin before they begin the regular study cycles (Cycles 1 and beyond). This will be called "Cycle 0." Participant 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. Participant will take metformin for 7-10 days in Cycle 0 before Cycle 1 begins. If participant is already taking metformin, they will continue their regular dose and start Day 1 of Cycle 1. If participant is already taking metformin but their dose is less than 1000mg/day, their dose will be slowly raised up to the study dose over the course of 7-10 days and then they will start Cycle 1. In Cycles 1 and beyond, all participants will take all 3 drugs at a time. Participant should take metformin with food. Starting in Cycle 1, participant will take everolimus 1 time a day by mouth at about the same time every day. Participant should take it either consistently with food every day or consistently without food every day. Starting in Cycle 1, participant will take letrozole 1 time a day by mouth at about the same time every day. It is very important for participant to take the study drugs just as the study doctor tells them. Participant should not skip any doses unless their study doctor tells them to skip doses. If participant throws up after taking the study drugs, they should NOT take another tablet that day. Participant should let their study doctor know that they got sick. If participant forgets to take the study drugs one day, they should not take any extra doses the next day. Participant should call their study doctor and ask for advice. There are 4 weeks in each cycle (except Cycle 0). Study Visits: Every cycle (+/- 10 days):

- Participant will have a physical exam, including measurement of their vital signs and

weight. This will include a pelvic exam if the disease can be felt in the pelvis.

- Participant's performance status will be recorded.

- Participant will be asked about any side effects they 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):

- Participant will have scans such as a CT scan and/or MRI to check the status of the

disease.

- If participant has chest disease, they will have a chest x-ray.

Length of Treatment: Participant may continue taking the study drugs for as long as the doctor thinks it is in their 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 they are unable to follow study directions. Patient's participation on the study will be over after the follow-up visits. End-of-Treatment Visit: After participant is finished taking the study drugs:

- Participant will have a physical exam, including a pelvic exam and measurement of their

vital signs and weight.

- Participant's performance status will be recorded.

- Participant will be asked about any side effects they may have had.

- Blood (about 2 tablespoons) will be drawn for routine tests.

- Participant will have scans such as a CT scan and/or MRI to check the status of the

disease.

- If participant has chest disease, they will have a chest x-ray.

Follow-Up Visits: Participant will have follow-up visits as often as the doctor thinks is needed. At every visit:

- Participant will have a physical exam, including measurement of their vital signs.

- Participant's performance status will be recorded.

- Participant will be asked about any side effects they may have had.

- If the doctor thinks it is needed, participant will have scans such as a CT scan and/or

MRI to check the status of the disease.

- If participant has chest disease, they will have a chest x-ray.

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

Eligibility

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria: 1. Patients must have histologically-confirmed advanced or recurrent endometrial carcinoma (endometrioid and mixed tumors, any grade) that is refractory to curative therapy or established treatments 2. Patients must have had no more than two prior chemotherapeutic regimens for recurrent management of endometrial carcinoma. Chemotherapy administered in conjunction with primary radiation as a radio-sensitizer is not counted as a prior treatment for recurrent or advanced disease 3. Prior radiation therapy of any kind is allowed 4. All patients must have measurable disease per RECIST 1. 1 defined as at least one target lesion that can be accurately measured in at least one dimension (>/=10mm longest dimension to be recorded; Lymph nodes must be >/=15 mm per short axis). Each lesion must be > 20 mm when measured by palpation or conventional imaging techniques

(CT or MRI - based on primary physician preference) or >10 mm with spiral CT scan.

Measurable lesions must be at least 2 times the slice thickness in millimeters. Tumors within a previously irradiated field will be designated as non-target lesions unless progression is documented. Ascites and pleural effusions are not considered measurable disease. If the measurable disease is confined to a solitary lesion, its neoplastic nature should be confirmed by cytology/histology 5. Patients must not be of child-bearing potential. Patients are considered not of child-bearing potential if they are surgically sterile (they have undergone a total hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or they are postmenopausal for greater than 12 months. Patients in whom ovaries are present and were not previously menopausal at the time of hysterectomy, should have a serum estradiol <10 pm/mL to confirm ovarian senescence. 6. Patients must be off all other anti-tumor therapies (including immunologic or hormonal agents) for at least four weeks prior to study registration. 7. Age >/= 18 years 8. GOG performance status /= 1. 5 x 10^9/L, Platelets >/= 100 x 10^9/L, Hb >9 g/dL 10. Adequate liver function as shown by: a. serum bilirubin 60 mL/min; Fasting serum cholesterol 10. CONTINUED FROM 10 - e. Liver disease such as cirrhosis or severe hepatic impairment

(Child-Pugh class C). Note: A detailed assessment of Hepatitis B/C medical history and risk factors must be done at screening for all patients. HBV DNA and HCV RNA PCR testing are required at screening for all patients with a positive medical history based on risk factors and/or confirmation of prior HBV/HCV infection; f. A known history of HIV seropositivity; g. Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of everolimus (e. g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or small bowel resection); h. Patients with an active, bleeding diathesis 11. Female patients who are pregnant or breast feeding, or adults of reproductive potential who are not using effective birth control methods. Adequate contraception must be used throughout the trial and for 8 weeks after the last dose of study drug, by both sexes. (Women of childbearing potential must have a negative urine or serum pregnancy test within 7 days prior to administration of everolimus) 12. Patients who have received prior treatment with an mTOR inhibitor (e. g., sirolimus, temsirolimus, everolimus). 13. Patients with a known hypersensitivity to everolimus or other rapamycins (e. g., sirolimus, temsirolimus) or to its excipients 14. History of noncompliance to medical regimens 15. Patients unwilling to or unable to comply with the protocol. 16. Patients with isolated recurrences (vaginal, pelvic, or paraaortic) that are amenable to potentially curative treatment with radiation therapy or surgery. 17. Patients with acute or chronic metabolic acidosis, lactic acidosis, or ketoacidosis. Note: during the study, metformin must be discontinued for 24 hours before and 48 hours after imaging involving IV contrast to minimize risk of lactic acidosis. 18. Patients who have hypoglycemia with a value of

Locations and Contacts

Pamela Soliman, MD, Phone: 713-745-2352

Sacred Heart Health Systems, Pensacola, Florida 32504, United States; Recruiting

MD Anderson Cooper Cancer Center, Township, New Jersey 08043, United States; Recruiting

Spartanburg Regional Health Care System, Spartanburg, South Carolina 29303, United States; Recruiting

Lyndon B Johnson General Hospital, Houston, Texas 77026, United States; Recruiting

Memorial City Medical Center, Houston, Texas 77024, United States; Recruiting

The Woman's Hospital of Texas, Houston, Texas 77054, United States; Recruiting

University of Texas MD Anderson Cancer Center, Houston, Texas 77030, United States; Recruiting

Additional Information

University of Texas MD Anderson Cancer Center Website

Starting date: October 2013
Last updated: May 12, 2015

Page last updated: August 23, 2015

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