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

Participants will receive a fixed dose of selinexor 60 milligrams (mg) oral tablets once weekly (QW) on Days 1, 8, 15, and 22 of each 28-day cycle.

Participants will receive matching placebo for selinexor oral tablets QW on Days 1, 8, 15, and 22 of each 28-day cycle.

Dose: 60 mg (3 tablets); Dosage form: film-coated, immediate-release tablet of 20 mg each; Route of administration: oral

Selinexor

Dose:60 mg (3 tablets); Dosage form: film-coated, immediate-release tablet of 20 mg each; Route of administration: oral

Matching Placebo for selinexor

Karyopharm Medical Information

Anna Wilbanks

Michael Toboni

Mei Yu

Lyndsay Willmott

Rachel Gray

Carolyn Haunschild

Laura Macias

Milan Sheth

Vanessa Lopez

Krishnansu Tewari

Bela Shah

Jonathan Berek

Julia Rivera Penafiel

John Chan

Michael Wacker

Bradley Corr

Toni Rodriquez

Scott Jordan

Krystal Olivera

Brian Slomovitz

Nina Kimball

Susan Modesitt

Trena Davis

Chelsea Chandler

Laura Lozano

Urszula Sobol

Cynthia Cruz Rivera

Michael Callahan

Amie Lake

LaToya Perry

Tammy Hines

Sobia Ozair

Cambri Moeller

Tara Castellano

Carrie Kay

Destin Black

Jill Marshall

Sarah Paraghamian

Allison Wolgast

Radhika Gogoi

Khadijra Lockwood

Christen Haygood

Megan Werner

Kristopher (Shawn) LyBarger

Jacky Amador

Nicola M Spirtos

Shannon Pierpoint

Peter Lim

Nicolina Suriano

Joyce Barlin

Karen Estok

Bhavana Pothuri

Neha Kumarley

Monica Prasad

Keith Kallas

Jennifer Mewshaw

Angeles A. Secord

Cara King

Amanda Jackson

Nancy Zangmeister

Emily Whitman-Purves

Kendra Mann

Natalie Walkup

Christine Pappaterra

Debra Richardson

Nora Auston

Christopher Darus

Siobhan Guyach

Sarah Crafton

Teri Kayl

David Starks

Kimberly Donelson

Stephen DePasquale

Amy Lange

Todd Tillmanns

Krissy Bolig

Larry Kilgore

Dominique Marquez

Brandon Sawyer

Annette Paulsen

David Miller

Jaya Kamath

Pedro Ramirez

Ben Singh

Antonio Santillan

Taryn Davis

Christine Lee

Angela Jennings

Anna Priebe

Rachel Lacy

Linda Duska

Claire Kostechka

Ellen Hartenbach

Paul Subarna

Elizabeth Hopp

Jacqui McBurnie

Christopher Steer

Jacquie Harvey

Michelle Harrison

Richard Clayton

Craig Kukard

Julie Charlton

Janine Lombard

Meenal Rai

Bo Gao

Monica Reay

Michael Slancar

Elizabeth Ratcliffe

Baskhar Karki

Holly Price

Allison Black

Karen Lim

Geraldine Goss

Karen Gillett

Kate Webber

Judi Clarke

Yoland Antill

Koby Scarff

Gary Richardson

Marian Lieschke

Linda Mileshkin

Anne Milton

Sudarsha Selva-Nayagam

Florence Fontaine

Jean-Francois Baurain

Sarah Van Damme

Daphne Serruys

Lauren van den Eynde

Toon Van Gorp

Marianne Blockmans

Nathalie Cornez

Benedicte Hyernaux

Stephanie Henry

Alison Avery

Katharina Kieser

Nithla Mohanathas

Al Covens

Bonny Choy

Vanessa Samouëlian

Nathalie Nguyen-Phuong-Nam

Lucy Gilbert

Katerina Polanska

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
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
Selinexor in Maintenance Therapy After Systemic Therapy for Participants With p53 Wild-Type, Advanced or Recurrent Endometrial Carcinoma	NCT05611931	Endometrial Can...	Selinexor Matching Placeb...	18 Years -	Karyopharm Therapeutics Inc

Spots Global Cancer Trial Database for advanced or recurrent endometrial carcinoma