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

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ClinicalTrials.gov Identifier: NCT03624244
Recruitment Status : Recruiting
First Posted : August 10, 2018
Last Update Posted : April 17, 2020
Sponsor:
Information provided by (Responsible Party):
Centre Leon Berard

Brief Summary:
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).

Condition or disease Intervention/treatment Phase
Low Grade Endometrial Stromal Sarcoma Drug: Aromatase Inhibitors Phase 2

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).

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Phase II comparative multicentre prospective randomised (1:1 ratio) open-label study
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Randomized Comparative Prospective Multicentre Phase II Trial Evaluating Clinical Impact of Interruption VS Maintenance of AI in Patients With Locally Advanced/ Metastatic LGESS
Actual Study Start Date : January 23, 2019
Estimated Primary Completion Date : October 2023
Estimated Study Completion Date : October 2023


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 Name: ANASTRAZOLE, ARIMIDEX, AROMASINE, EXEMESTANE, FEMARA, LETROZOLE

Maintenance of aromatase inhibitors
Maintenance of aromatase inhibitors
Drug: Aromatase Inhibitors
Maintenance of AI versus interruption of AI
Other Name: ANASTRAZOLE, ARIMIDEX, AROMASINE, EXEMESTANE, FEMARA, LETROZOLE




Primary Outcome Measures :
  1. 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


Secondary Outcome Measures :
  1. Overall survival [ Time Frame: From date of randomization to death due to any cause, assessed up to 60 months ]
    Overall survival

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Gender Based Eligibility:   Yes
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03624244


Contacts
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Contact: Séverine METZGER +33478782786 severine.metzger@lyon.unicancer.fr
Contact: Isabelle RAY-COQUARD, MD PhD +33478782828 isabelle.ray-coquard@lyon.unicancer.fr

Locations
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Sponsors and Collaborators
Centre Leon Berard
Investigators
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Principal Investigator: Isabelle RAY-COQUARD, MD PhD Centre Leon Berard
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Responsible Party: Centre Leon Berard
ClinicalTrials.gov Identifier: NCT03624244    
Other Study ID Numbers: ET17-200 BRF-ESS
First Posted: August 10, 2018    Key Record Dates
Last Update Posted: April 17, 2020
Last Verified: April 2020

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Centre Leon Berard:
Low Grade Endometrial Stromal Sarcoma
Aromatase inhibitors
Additional relevant MeSH terms:
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Sarcoma
Sarcoma, Endometrial Stromal
Endometrial Stromal Tumors
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Complex and Mixed
Endometrial Neoplasms
Uterine Neoplasms
Uterine Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Urogenital Neoplasms
Neoplasms, Connective Tissue
Letrozole
Exemestane
Aromatase Inhibitors
Antineoplastic Agents
Steroid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Estrogen Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs