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

August 31, 2023 updated by: Centre Leon Berard

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

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).

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

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).

Study Type

Interventional

Enrollment (Estimated)

40

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Age≥18 years;
  • Histological confirmation of low grade ESS;
  • Locally advanced or metastatic disease at diagnosis or patient experiencing a tumor effraction during hysterectomy;
  • Treatment with aromatase inhibitors (Anastrozole or Exemestane or Letrozole ) initiated either: for at least 24 months (in patients with no residual disease or non-measurable disease at the last AI initiation) OR for at least 36 months (in patients with measurable disease at the last AI initiation);
  • Disease must be controlled at the time of the randomisation (objective response or stable disease) by the aromatase inhibitor initiated either for at least 24 or 36 months
  • Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) ≤ 2
  • Covered by a medical insurance;
  • Signed informed consent prior to any study-specific procedure.

Exclusion Criteria:

  • Pregnant or breastfeeding woman;
  • Patient concurrently using other approved or investigational antineoplastic agents;
  • Major concurrent disease affecting cardiovascular system, liver, kidneys, hematopoietic system or else considered as clinically important by the investigator and that could be incompatible with patient's participation in this trial or would likely interfere with study procedures or results;
  • Prior history of malignancies other than study disease (except for basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix) unless the patient has been free of the disease for at least 3 years;
  • Patients using prohibited concomitant and/or concurrent medications
  • Contra-indication according to SmPCs.
  • Patient requiring tutorship or curatorship.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Interruption of aromatase inhibitors
Interruption of aromatase inhibitors until progression disease. At disease progression, AI can be reintroduced.
Drug: Aromatase Inhibitors
Maintenance of AI versus interruption of AI
Other Names:
  • ANASTRAZOLE, ARIMIDEX, AROMASINE, EXEMESTANE, FEMARA, LETROZOLE
Other: Maintenance of aromatase inhibitors
Drug: Aromatase Inhibitors
Maintenance of AI versus interruption of AI
Other Names:
  • ANASTRAZOLE, ARIMIDEX, AROMASINE, EXEMESTANE, FEMARA, LETROZOLE

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression free survival
Time Frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 months
Progression free survival
From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall survival
Time Frame: From date of randomization to death due to any cause, assessed up to 60 months
Overall survival
From date of randomization to death due to any cause, assessed up to 60 months
Time to first subsequent chemotherapy/treatment or death
Time Frame: From date of randomization to the earliest date of chemotherapy/treatment start date following study treatment discontinuation, or death due to any cause, whichever came first, assessed up to 60 months
Time to first subsequent chemotherapy/treatment or death
From date of randomization to the earliest date of chemotherapy/treatment start date following study treatment discontinuation, or death due to any cause, whichever came first, assessed up to 60 months
Objective response rate after reintroduction of AI in the experimental arm
Time Frame: From the date of AI reintroduction in the experimental arm to the date of subsequent progression or date of death due to any cause, whichever came first, assessed up to 60 months
Proportion of patients with a best overall response of Partial Response (PR) or Complete Response (CR) after AI reintroduction in the experimental arm
From the date of AI reintroduction in the experimental arm to the date of subsequent progression or date of death due to any cause, whichever came first, assessed up to 60 months
Progression free survival after reintroduction of AI in the experimental arm
Time Frame: From the date of AI reintroduction in the experimental arm to the date of subsequent progression or date of death due to any cause, whichever came first, assessed up to 60 months
Progression free survival after reintroduction of AI in the experimental arm
From the date of AI reintroduction in the experimental arm to the date of subsequent progression or date of death due to any cause, whichever came first, assessed up to 60 months
Duration of response to AI after reintroduction
Time Frame: From the date of first objective response following the reintroduction of AI to the date of the first subsequent documented radiological progression or death due to any cause, whichever came first, assessed up to 60 months
Duration of response to AI after reintroduction
From the date of first objective response following the reintroduction of AI to the date of the first subsequent documented radiological progression or death due to any cause, whichever came first, assessed up to 60 months
Incidence of Treatment-Emergent Adverse Events
Time Frame: From date of randomization to follow-up visit Month 36 or death due to any cause, whichever came first, assessed up to 60 months
Safety and Tolerability assessed according to the NCI-CTC AE version 5
From date of randomization to follow-up visit Month 36 or death due to any cause, whichever came first, assessed up to 60 months
Quality of Life using European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30)
Time Frame: Every 6 months until the 36th month for each patient
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.
Every 6 months until the 36th month for each patient

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Centre Leon Berard

Investigators

  • Principal Investigator: Isabelle RAY-COQUARD, MD PhD, Centre Leon Berard

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 23, 2019

Primary Completion (Estimated)

January 1, 2025

Study Completion (Estimated)

January 1, 2028

Study Registration Dates

First Submitted

July 18, 2018

First Submitted That Met QC Criteria

August 8, 2018

First Posted (Actual)

August 10, 2018

Study Record Updates

Last Update Posted (Actual)

September 1, 2023

Last Update Submitted That Met QC Criteria

August 31, 2023

Last Verified

August 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ET17-200 BRF-ESS

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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