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

Phase 2

Completed

• Conditions: Breast Cancer
• Interventions: Drug: Estramustine; Drug: Tamoxifen

• Registration Number: NCT02866955
• Lead Sponsor: Institut de Cancérologie de Lorraine

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2011-06-15
• Primary Completion: 2014-08-08
• Study Completion: 2015-08-28
• Study First Submitted: 2016-08-08
• Study First Submitted QC: 2016-08-10
• Study First Posted: 2016-08-15
• Status Verified: 2020-03
• Last Update Submitted: 2020-03-06
• Last Update Posted: 2020-03-09

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 100

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
GROUP E (Estramustine)	Estramustine	Patients with HER2-/RH+ breast cancer progressing after having already undergone a first line adjuvant treatment by estramustine
GROUP T (Tamoxifen)	Tamoxifen	Patients with HER2-/RH+ breast cancer progressing after having already undergone a first line adjuvant treatment by tamoxifen

Primary Outcome Measures

Name	Time	Method
Progression-free survival after a 6- month monotherapy with Estramustine in patients with HER2-/RH+ breast cancer progressing	up to 6 months	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

Secondary Outcome Measures

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

Trial Locations

Locations (21)

Institut Sainte Catherine; 🇫🇷 Avignon, France

Institut de Cancérologie de Lorraine; 🇫🇷 Vandoeuvre-lès-Nancy, France

CHU Besançon-Jean Minjoz; 🇫🇷 Besançon, France

CLCC Léon Bérard; 🇫🇷 Lyon, France

Polyclinique de Blois; 🇫🇷 Blois, France

CHU Avicenne; 🇫🇷 Bobigny, France

Polyclinique Bordeaux Nord Aquitaine; 🇫🇷 Bordeaux, France

CHRU Brest; 🇫🇷 Brest, France

Hôpital Privé Clairval; 🇫🇷 Marseille, France

Centre O. Lambret; 🇫🇷 Lille, France

CLCC Val d'Aurel; 🇫🇷 Montpellier, France

CHBM Site du Mittan; 🇫🇷 Montbeliard, France

Centre Catherine de Sienne; 🇫🇷 Nantes, France

Centre Antoine Lacassagne; 🇫🇷 Nice, France

CHU Tenon; 🇫🇷 Paris, France

Hôpital Européen Georges Pompidou; 🇫🇷 Paris, France

Polyclinique Courlancy Reims; 🇫🇷 Reims, France

Institut Jean Godinot; 🇫🇷 Reims, France

Clinique Sainte Anne; 🇫🇷 Strasbourg, France

Clinique armoricaine; 🇫🇷 Saint Brieuc, France

Centre Paul Strauss; 🇫🇷 Strasbourg, France