Evaluation of the Efficacy of Estramustine in Patient With Breast Cancer Progression After Treatment With Aromatase Inhibitor. (EFESE)

Despite advances in early detection and treatment strategy, about 25 to 40% of patients treated for breast cancer develop metastasis.

Some patients are in a therapeutic impasse situation. It is therefore necessary to consider all possible options. The Estramustine showed encouraging results in the treatment of metastatic breast cancer.

Given the clinical data, the answer rate of Estramustine and its impact on progression free survival deserve to be studied in earlier clinical situation.

This Phase II study evaluated the efficacy of Estramustine in women with breast cancer and metastates, already treated with aromatase inhibitors and for whom this treatment has failed.

Study Overview

• Status: Completed
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: Estramustine; Drug: Tamoxifen

• Study Type: Interventional
• Enrollment (Actual): 100
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Avignon, France, 84082
    • Institut Sainte Catherine
  • Besançon, France, 25030
    • CHU Besançon-Jean Minjoz
  • Blois, France, 41260
    • Polyclinique De Blois
  • Bobigny, France, 93009
    • CHU Avicenne
  • Bordeaux, France, 33077
    • Polyclinique Bordeaux Nord Aquitaine
  • Brest, France, 29200
    • CHRU Brest
  • Lille, France, 59020
    • Centre O. Lambret
  • Lyon, France, 69373
    • CLCC Léon Bérard
  • Marseille, France, 13009
    • Hôpital privé Clairval
  • Montbeliard, France, 25200
    • CHBM Site du Mittan
  • Montpellier, France, 34298
    • CLCC Val d'Aurel
  • Nantes, France, 44202
    • Centre Catherine de Sienne
  • Nice, France, 06189
    • Centre Antoine Lacassagne
  • Paris, France, 75908
    • Hopital Europeen Georges Pompidou
  • Paris, France, 75020
    • CHU Tenon
  • Reims, France, 51056
    • Institut Jean Godinot
  • Reims, France, 51100
    • Polyclinique Courlancy Reims
  • Saint Brieuc, France, 22015
    • Clinique Armoricaine
  • Strasbourg, France, 67000
    • Centre Paul Strauss
  • Strasbourg, France, 67085
    • Clinique Sainte Anne
  • Vandoeuvre-lès-Nancy, France, 54519
    • Institut de Cancérologie de Lorraine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Post-menopausal women or women receiving Luteinizing hormone-releasing hormone (LHRH) analogs
• Histologically confirmed metastatic breast cancer RH+
• Measurable metastatic breast cancer (modified RECIST criteria) or not measurable but evaluable

• Recurrence:

  • being treated with aromatase inhibitors (AIs)
  • after adjuvant treatment by AIs
  • after progression of the metastatic cancer in patients receiving AIs following positive response during at least 6 months
• Performance status ≤ 2
• Haematological test: polynuclear neutrophiles ≥ 1.5 × 109 /L, haemoglobin ≥ 9 g/dL, blood platelet ≥ 100 × 109 /L
• Hepatic function: albumin ≥ 2.5 g/dL, serum bilirubin ≤ 1.5 × N (except if Gilbert's Syndrome) , aminotransferases ≤ 3 × N (≤ 5 × N if hepatic metastases)
• Renal function: serum creatinine ≤ 1.5 mg/dL or clearance of creatinine ≥ 40 ml/min
• Women without endometrial pathology
• Ability to provide written informed consent before the start of any study specific procedures

Exclusion Criteria:

• Age < 18 years old
• Pre-menopausal, pregnant or pregnant or breast feeding females
• Patient who should exclusively be treated by chemotherapy
• Women previously treated with chemotherapy but not by AIs
• Women previously treated by tamoxifen for their metastatic breast cancer
• HER2+
• Concurrent anti-cancer treatment (chemotherapy, surgery, immunotherapy, biological therapy and tumour embolism)
• Concurrent treatment with protocol-defined prohibited medications
• Malabsorption syndrome , significant digestive dysfunction, gastrectomy, jejunectomy, hemorrhagic recto colon
• Concurrent disease or condition that may interfere with study participation, or any serious medical disorder that would interfere with the subject's safety (for example, active or uncontrolled infection or any psychiatric condition prohibiting understanding or rendering of informed consent)
• Any pathology, including severe psychiatric or psychologic disease that may harm patient's safety or participation in the study
• Serious or not cured or unstable toxicity due to the administration of another drug being involved in clinical trials
• Uncontrolled cardiovascular pathologies
• Previous history of thromboembolic event like deep vein thrombosis or pulmonary embolism recorded within one year before the inclusion date
• Active uncontrolled infection

• Existence of an increased risk of thromboembolic event, apart from the metastatic cancer condition, such as:

  • known presence of antiphospholipid antibody
  • family history of thrombophilia
  • existence of any clinical, genetic, or biological abnormality which can increase the risk of thromboembolic event according to the
• Participation to a clinical trial at least 4 weeks prior the start of the study

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: GROUP E (Estramustine); Patients with HER2-/RH+ breast cancer progressing after having already undergone a first line adjuvant treatment by estramustine	Drug: Estramustine; 140mg/4 caps/day; Other Names: estramustine phosphate
Other: GROUP T (Tamoxifen); Patients with HER2-/RH+ breast cancer progressing after having already undergone a first line adjuvant treatment by tamoxifen	Drug: Tamoxifen; 20mg/day

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival after a 6- month monotherapy with Estramustine in patients with HER2-/RH+ breast cancer progressing	proportion of patients in progression-free survival (PFS) after a 6-month treatment is defined as the duration of objective response or stabilisation of the disease according to the Recist criteria. The following events shall be considered as progressive : Relapse; Treatment intolerance leading to stop the treatment; Death	up to 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Risks of thrombosis	risks of thrombosis assessed by the analysis of biomarkers (D-Dimer, prothrombin fragment 1+2, von Willebrand factor, fibrinogen, Chain Reaction Protein)	up to 6 months
Clinical benefit of estramustine	clinical benefit of estramustine assessed by RECIST criteria	1 year
Correlation between the answer rate and biomarkers	answer rate (RECIST criteria) and level of biomarkers (Lactate déshydrogénase, Antigène carcino-embryonnaire and Cancer antigène 15-3)	1 year
Tolerance of estramustine treatment	Toxicity (Common Terminology Criteria for Adverse Events)	1 year
Tolerance of tamoxifen treatments	Toxicity (Common Terminology Criteria for Adverse Events)	1 year
Proportion of patients developing thromboembolic events	proportion of patients developing thromboembolic events assessed in the 2 groups every month during the one-year patient follow-up	1 year

Collaborators and Investigators

• Sponsor: Institut de Cancérologie de Lorraine
• Investigators: Principal Investigator: LUPORSI Elisabeth, MD, Institut de Cancérologie de Lorraine; Principal Investigator: GUASTALLA Jean Paul, MD, CLCC Léon Bérard

Study record dates

Study Major Dates

• Study Start (Actual): June 15, 2011
• Primary Completion (Actual): August 8, 2014
• Study Completion (Actual): August 28, 2015

Study Registration Dates

• First Submitted: August 8, 2016
• First Submitted That Met QC Criteria: August 10, 2016
• First Posted (Estimate): August 15, 2016

Study Record Updates

• Last Update Posted (Actual): March 9, 2020
• Last Update Submitted That Met QC Criteria: March 6, 2020
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Keywords: aromatase inhibitors; Metastases
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Antineoplastic Agents, Alkylating; Alkylating Agents; Hormone Antagonists; Bone Density Conservation Agents; Estrogen Antagonists; Selective Estrogen Receptor Modulators; Estrogen Receptor Modulators; Tamoxifen; Estramustine
• Other Study ID Numbers: 2009-017788-40

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No