Neoplasms

All Conditions

Symptoms and General Pathology

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

Rare Diseases

Carcinoma

Adenocarcinoma

Recurrence

Endometrial Neoplasms

Carcinoma, Endometrioid

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Disease Attributes

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

Ovarian Neoplasms

Ovarian Diseases

Adnexal Diseases

Gonadal Disorders

Endocrine System Diseases

Ovarian Cancer

Antineoplastic Agents

All Drugs and Chemicals

Anti-Infective Agents

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 receive ribociclib PO QD, everolimus PO QD, and letrozole PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Patients receive everolimus PO QD and letrozole PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Ribociclib

Pamela T Soliman

This phase II trial studies how well everolimus and letrozole with or without ribociclib work in treating participants with endometrial cancer that has spread to other areas of the body or has come back. Ribociclib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs such as everolimus and letrozole have been shown to be effective at stopping tumor growth either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving ribociclib, everolimus, and letrozole may work better than everolimus and letrozole in treating participants with endometrial cancer.

PRIMARY OBJECTIVE:

I. To determine if the addition of ribociclib (LEE011) to everolimus and letrozole improves progression free survival in patients with advanced or recurrent endometrial carcinoma.

SECONDARY OBJECTIVES:

I. To determine clinical benefit and the median duration of progression-free survival (PFS) and overall survival (OS) in patients with advanced or recurrent endometrial carcinoma treated with ribociclib (LEE011), everolimus and letrozole versus everolimus and letrozole alone.

II. To determine the frequency and severity of toxicities associated with ribociclib (LEE011), everolimus (RAD001), and letrozole in this cohort of patients.

III. To determine the presence of a CTNNB1 mutation is associated with response to ribociclib (LEE011), everolimus (RAD001), and letrozole.

IV. To determine if liquid biopsies at baseline and 8 weeks correlate with presence of a tissue mutation or response to therapy.

EXPLORATORY OBJECTIVE:

I. To examine the pharmacokinetic and pharmacodynamic effects of ribociclib in patients with advanced or recurrent endometrial carcinoma.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients receive ribociclib orally (PO) once daily (QD), everolimus PO QD, and letrozole PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive everolimus PO QD and letrozole PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, participants are followed up at 30 days and then every 3 months.

A Phase II, Two-Arm Study of Everolimus and Letrozole, +/- Ribociclib (Lee011) in Patients With Advanced or Recurrent Endometrial Carcinoma

A Phase II, Randomized Two-Arm Study of Everolimus and Letrozole, +/- Ribociclib (LEE011) in Patients With Advanced or Recurrent Endometrial Carcinoma

Per Response Evaluation Criteria in Solid Tumors version 1.1. This will be determined by combining the complete response rate, partial response rate, and stable disease rate. Response will be evaluated by repeat imaging (computed tomography or magnetic resonance imaging). Fisher's exact test will be used to compare patients with/without CTNNB1 mutation with respect to CBR.

M.D. Anderson Cancer Center

Cystadenocarcinoma, Serous

Adenocarcinoma, Clear Cell

Cystadenocarcinoma

Neoplasms, Cystic, Mucinous, and Serous

Adenocarcinoma of the Appendix

Reproductive Control Agents

Anastrozole

Progesterone

Onapristone

Progestins

Antineoplastic Agents, Hormonal

Patients receive onapristone PO BID and anastrozole PO QD on days 1-28. Treatment repeats every 28 days for up to 24 cycles (24 months) until November 30, 2023 or in the absence of disease progression or unacceptable toxicity.

Extended-release Onapristone

Quality-of-Life Assessment

Questionnaire Administration

Immunohistochemistry (IHC):Integral : Tissue

Estrogen Receptor Positive (Positive Estrogen Receptor; ESR Positive; ESR1 Positive; ER Positive; Estrogen Receptor Alpha Positive)

Progesterone Receptor Positive ( PGR Positive; PR Positive)

Russell Schilder, MD

This phase II trial studies the effect of onapristone and anastrozole in treating patients with hormone receptor positive endometrial cancer that has not responded to previous treatment (refractory). Progesterone and estrogen are hormones that can cause the growth of endometrial cancer cells. Onapristone blocks the use of progesterone by the tumor cells. Anastrozole is a drug that blocks the production of estrogen in the body. Giving onapristone with anastrozole may work better than anastrozole alone in treating patients with hormone receptor positive endometrial cancer.

PRIMARY OBJECTIVE:

I. To evaluate the activity and safety of a pure progesterone receptor (PR) antagonist, extended-release onapristone (onapristone), with anastrozole to treat women with recurrent metastatic estrogen receptor positive (ER+)/progesterone receptor positive (PR+) endometrial carcinoma.

SECONDARY OBJECTIVES:

I. To estimate the disease control rate (DCR). II. To describe duration of response (DOR). III. To evaluate the safety and tolerability. IV. To evaluate quality of life using the Edmonton Symptom Assessment questionnaire.

EXPLORATORY OBJECTIVES:

I. To characterize the ER and PR expression by immunohistochemistry (IHC) pre- and post-treatment.

OUTLINE:

Patients receive onapristone orally (PO) twice daily (BID) and anastrozole PO once daily (QD) on days 1-28. Treatment repeats every 28 days for up to 24 cycles (24 months) in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for up to 1 year after last treatment administration.

Onapristone and Anastrozole for the Treatment of Refractory Hormone Receptor Positive Endometrial Cancer

A Phase II Clinical Trial Evaluating the Combination of Onapristone With Anastrozole for Women With Refractory Hormone Receptor Positive Endometrial Cancer

Assessed by immunohistochemistry and represented as a percentage prior to trial initiation and at progression.

Defined by the percentage of patients with tumor response (complete response \[CR\] or partial response \[PR\]) as defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.

4 month PFS is defined as a binary endpoint, from first dose of onapristone and anastrozole to 4 months of therapy as "confirmed progression-free" or "not progression-free" (including cancer progression or censored subjects). Will use the date of first documented disease progression or recurrence, as assessed by using RECIST 1.1 criteria, or death due to any cause, whichever occurs first.

Defined as best overall response of CR, PR, or stable disease lasting for \>= 24 weeks, per RECIST 1.1.

Adverse events will be graded for severity according to the Common Terminology Criteria for Adverse Events version 5.0.

Quality of life and pain scores are defined by the Edmonton Symptom Assessment System using nine subjective patient measures of well-being including pain, tiredness, nausea, depression, anxiety, drowsiness, appetite, well-being, shortness of breath.

Context Therapeutics Inc.

Thomas Jefferson University

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
A Phase II, Two-Arm Study of Everolimus and Letrozole, +/- Ribociclib (Lee011) in Patients With Advanced or Recurrent Endometrial Carcinoma	NCT03008408	Recurrent Endom... Recurrent Endom... Refractory Endo... Refractory Endo... Stage III Uteri... Stage IIIA Uter... Stage IIIB Uter... Stage IIIC Uter... Stage IIIC1 Ute... Stage IIIC2 Ute... Stage IV Uterin... Stage IVA Uteri... Stage IVB Uteri...	Everolimus Letrozole Ribociclib	18 Years -	M.D. Anderson Cancer Center
Onapristone and Anastrozole for the Treatment of Refractory Hormone Receptor Positive Endometrial Cancer	NCT04719273	Refractory Endo... Refractory Endo... Refractory Endo... Refractory Endo... Refractory Endo... Refractory Endo... Refractory Endo...	Extended-releas... Anastrozole Quality-of-Life... Questionnaire A... Estrogen Recept... Progesterone Re...	18 Years -	Thomas Jefferson University

Spots Global Cancer Trial Database for refractory endometrial endometrioid adenocarcinoma