Clinical trial NCT02866955: Evaluation of the Efficacy of Estramustine in Patient With Breast Cancer Progression After Treatment With Aromatase Inhibitor.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Breast Cancer
Keywords: aromatase inhibitors
Metastases
Lead sponsor: Institut de Cancérologie de Lorraine
Sponsor class: OTHER
First posted: 2016-08-15
Enrollment: 100
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Progression-free survival after a 6- month monotherapy with Estramustine in patients with HER2-/RH+ breast cancer progressing
timeFrame: up to 6 months
Secondary outcomes:
measure: Risks of thrombosis
timeFrame: up to 6 months
measure: Clinical benefit of estramustine
timeFrame: 1 year
measure: Correlation between the answer rate and biomarkers
timeFrame: 1 year
measure: Tolerance of estramustine treatment
timeFrame: 1 year
measure: Tolerance of tamoxifen treatments
timeFrame: 1 year
measure: Proportion of patients developing thromboembolic events
timeFrame: 1 year
Other outcomes:
Locations:
city: Avignon
country: France
facility: Institut Sainte Catherine
city: Besançon
country: France
facility: CHU Besançon-Jean Minjoz
city: Blois
country: France
facility: Polyclinique de Blois
city: Bobigny
country: France
facility: CHU Avicenne
city: Bordeaux
country: France
facility: Polyclinique Bordeaux Nord Aquitaine
city: Brest
country: France
facility: CHRU Brest
city: Lille
country: France
facility: Centre O. Lambret
city: Lyon
country: France
facility: CLCC Léon Bérard
city: Marseille
country: France
facility: Hôpital Privé Clairval
city: Montbeliard
country: France
facility: CHBM Site du Mittan
city: Montpellier
country: France
facility: CLCC Val d'Aurel
city: Nantes
country: France
facility: Centre Catherine de Sienne
city: Nice
country: France
facility: Centre Antoine Lacassagne
city: Paris
country: France
facility: CHU Tenon
city: Paris
country: France
facility: Hôpital Européen Georges Pompidou
city: Reims
country: France
facility: Institut Jean Godinot
city: Reims
country: France
facility: Polyclinique Courlancy Reims
city: Saint Brieuc
country: France
facility: Clinique armoricaine
city: Strasbourg
country: France
facility: Centre Paul Strauss
city: Strasbourg
country: France
facility: Clinique Sainte Anne
city: Vandoeuvre-lès-Nancy
country: France
facility: Institut de Cancérologie de Lorraine
Study officials:
affiliation: Institut de Cancérologie de Lorraine
name: LUPORSI Elisabeth, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: CLCC Léon Bérard
name: GUASTALLA Jean Paul, MD
role: PRINCIPAL_INVESTIGATOR
References: