Neoplasms

All Conditions

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Skin and Connective Tissue Diseases

Rare Diseases

Sarcoma

Sarcoma, Endometrial Stromal

Endometrial Stromal Tumors

Neoplasms, Connective and Soft Tissue

Neoplasms by Histologic Type

Endometrial Neoplasms

Uterine Neoplasms

Uterine Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Genital Neoplasms, Female

Urogenital Neoplasms

Neoplasms, Connective Tissue

Soft Tissue Sarcoma

Endometrial Stromal Sarcoma

Antineoplastic Agents

All Drugs and Chemicals

Exemestane

Letrozole

Anastrozole

Aromatase Inhibitors

Enzyme Inhibitors

Estrogens

Estrogen Antagonists

Estrogen Receptor Antagonists

Hormones

Hormone Antagonists

Interruption of aromatase inhibitors until progression disease. At disease progression, AI can be reintroduced.

Maintenance of AI versus interruption of AI

Séverine METZGER

Isabelle RAY-COQUARD, MD PhD

Loic CHAIGNEAU, MD

FLOQUET Anne

Sabine NOAL, MD

Pascale DUBRAY-LONGERAS

Nicolas PENEL, MD

VENAT-BOUVET Laurence

Florence DUFFAUD

Florence DUFFAUD, MD

BERTUCCI François

Michel FABBRO

Esma SAADA-BOUZID

Jean-Philippe SPANO

ALEXANDRE Jérôme

WATSON Sarah, MD

SAVOYE Aude-Marie

GUILLEMET Cécile

Emmanuelle BOMPAS

FOURNEL Pierre, MD

Olivier COLLARD, MD

Hélène VEGAS

Patricia PAUTIER, MD

The primary objective is to compare the progression-free survival (PFS) between aromatase inhibitors interruption and aromatase inhibitors maintenance strategies in patients with a locally advanced or metastatic Low Grade Endometrial Stromal Sarcoma (LGESS).

Uterine sarcomas are rare tumors with an incidence of 1.7/100 000 women per year, including 20% of endometrial stromal sarcomas (ESS). Patients with low grade ESS (LGESS) have a good prognosis with a 5-year overall survival rates ranging from 66 to 98%, depending on the stage of the disease.

Majority of LGESS report estrogen receptor (ER) and/or progesterone receptor positive and a chromosomal translocation with JAZF1-SUZ12.

Based on the current European Society of Medical Oncology (ESMO)guidelines, the standard treatment for patients with early/non metastatic ESS is total hysterectomy plus or less bilateral salpingo-oophorectomy. The use of hormonal therapy (HT) for advanced or metastatic disease is recommended based on retrospective data from small series providing evidence that HT have an anti-tumor activity on LGESS. HT includes aromatase inhibitors (AI), progestins and gonadotrophin-releasing hormone.

Very few data are available in this rare disease, but retrospective analyses show that AI may provide response rates of 46 to 67% in metastatic LGESS patients (7% complete response, 60% partial response), with a mean duration of response of 24 months.

Even if AI are effective and well tolerated, chronical mild to moderate (grade 1-2) side-effects (arthritis, hot-flashes, osteoporosis, hypercholesterolemia, cardiac events) have a negative impact on patient's well-being because of the treatment long term duration and need to be balanced in such long term survival.

To date, the question of the optimal duration of HT in LGESS is still pending. The investigator propose an open-label, randomized, multicenter phase II study aiming at determining the feasibility of interruption of AI in patients with locally advanced or metastatic LGESS after long term stabilization or response to AI. The study will use a sequential bayesian design allowing for continuous monitoring of the main efficacy outcome, thus leading to a smaller more informative trial, and specifically tied to decision making. This design is particularly suited to characterize efficacy signals in the context of a very rare pathology. Moreover JAZF1-JJAZ1 fusion gene is not identified in all LGESS.

Ancillary studies will provide precious data aiming at:

* Identifying predictive factors of prolonged response to HT or late resistance (Next Generation Sequencing and Comparative Genome Hybridization).
* Evaluating sociobehavioral (only for French sites) of patients by following questionnaire: Zimbardo Time Perspective Inventory (ZTPI) , Functional, Communicative and Critical Health Literacy/ 14-item Health Literacy Scale (FCCHL/HLS14), VICAN, Fear of Cancer Recurrence (FCR) and Patient-Generated Index (PGI).

Phase II comparative multicentre prospective randomised (1:1 ratio) open-label study

Evaluation of Clinical Impact of Interruption VS Maintenance of AI in Patients With Locally Advanced/ Metastatic Low Grade Endometrial Stromal Sarcoma (LGESS)

Randomized Comparative Prospective Multicentre Phase II Trial Evaluating Clinical Impact of Interruption VS Maintenance of AI in Patients With Locally Advanced/ Metastatic LGESS

Time to first subsequent chemotherapy/treatment or death

Proportion of patients with a best overall response of Partial Response (PR) or Complete Response (CR) after AI reintroduction in the experimental arm

Progression free survival after reintroduction of AI in the experimental arm

Duration of response to AI after reintroduction

Safety and Tolerability assessed according to the NCI-CTC AE version 5

Quality of Life using EORTC QLQ-C30 questionnaire. 64 questions related to cancer impact on health and daily activities composed this questionnaire. Each item has to be graded from 1 to 4 ( 1 = not at all; 4 = very much). More the score is high, worst the quality of life is.

Centre Leon Berard

Symptoms and General Pathology

Adenocarcinoma

Recurrence

Reproductive Control Agents

Mifepristone

Contraceptive Agents

Contraceptives, Oral

Contraceptive Agents, Female

Contraceptives, Postcoital

Contraceptive Agents, Hormonal

Lois M. Ramondetta, MD

Primary Objectives:

1. To determine the antitumor activity of Mifepristone (RU-486) in patients with advanced or recurrent endometrioid adenocarcinoma or low grade endometrial stromal sarcoma (LGESS).
2. To evaluate the quantitative and qualitative toxicities of Mifepristone in this patient population.
3. To evaluate at a tissue level the effect of Mifepristone on estrogen and progesterone receptors post treatment and to evaluate other markers that may reflect effects of Mifepristone on cancer cell growth.
4. To evaluate the effect of the agent and dosing schedule on the patient's quality of life.

Mifepristone is a drug that has been approved for use in the termination of pregnancy. It has been studied in women with breast and ovarian cancer.

Before treatment starts, patients will have a complete checkup, blood tests, a CT scan, and a chest x-ray. Women able to have children must have a negative urine pregnancy test. Blood tests and a complete checkup will also be done within 3 days of starting each course of therapy and a month after treatment ends. Tumors will be measured by CT scans once every 2-3 months and at the end of treatment.

Patients in this study will take Mifepristone in the form of a pill by mouth every day. Each course of therapy is 4 weeks long. Patients will see their doctor for an exam and blood tests before they begin each 4 week course of therapy. The dose of Mifepristone may be lowered if the patient has side effects. Patients who have a complete response (there is no evidence of cancer by physical exam or x-ray) will continue taking Mifepristone for 2 years after this response is documented. Other patients will take Mifepristone for as long as it benefits them.

This is an investigational study. At least 12 and as many as 37 patients will take part in this study. Patients from MD Anderson Cancer Center and Gynecologic Oncology of Houston, P.A. will be enrolled.

Mifepristone for Patients With Endometrial Cancer and LGESS

Phase II Study of Mifepristone (RU-486) in the Treatment of PR Positive Advanced/Recurrent Endometrioid Adenocarcinoma and Low Grade Endometrial Stromal Sarcoma (LGESS)

Overall Response = Complete and Partial Responses

M.D. Anderson Cancer Center

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Evaluation of Clinical Impact of Interruption VS Maintenance of AI in Patients With Locally Advanced/ Metastatic Low Grade Endometrial Stromal Sarcoma (LGESS)	NCT03624244	Low Grade Endom...	Aromatase Inhib...	18 Years -	Centre Leon Berard
Mifepristone for Patients With Endometrial Cancer and LGESS	NCT00505739	Endometrial Can...	Mifepristone	-	M.D. Anderson Cancer Center
Mifepristone for Patients With Endometrial Cancer and LGESS	NCT00505739	Endometrial Can...	Mifepristone	-	M.D. Anderson Cancer Center
Evaluation of Clinical Impact of Interruption VS Maintenance of AI in Patients With Locally Advanced/ Metastatic Low Grade Endometrial Stromal Sarcoma (LGESS)	NCT03624244	Low Grade Endom...	Aromatase Inhib...	18 Years -	Centre Leon Berard

Spots Global Cancer Trial Database for low grade endometrial stromal sarcoma