Everolimus and Fulvestrant therapy in postmenopausal metastatic Breast Cancer at patient treated with fulvestrant and who progressed on or after mTor inhibitor based treatment

• Conditions: postmenopausal women with hormone receptor-positive, Her2 negative AI and fulvestrant treated, locally advanced or metastatic breast cancer, who progressed on prior fulvestrant and also received prior treatment with everolimus and exemestane. The treatment with fulvestrant is not required to be the last treatment administered as long as at some point in time a progression on fulvestrant has been ascertained.; MedDRA version: 14.1Level: LLTClassification code 10027475Term: Metastatic breast cancerSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2013-000665-36-BE
• Lead Sponsor: Z Brussel

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2013-07-16
• Last Update Posted: 7 October 2014

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: Female
• Target Recruitment: Not specified

Inclusion Criteria

1. Postmenopausal women. Postmenopausal status is defined either by:
- Age = 55 years and one year or more of amenorrhea
- Age < 55 years and one year or more of amenorrhea, with an estradiol assay < 20 pg/ml
- Surgical menopause with bilateral oophorectomy
2. Organ function:
- ALT/AST <2.5 ULN or <5 if hepatic metastases
- Bilirubine less than 2.5 ULN
- PLT > 100.000 10*6/L
- WBC >3.5 and ANC> 1.5 10*9 g/L
- Hb > 9.0 g/dL
- INR < 2
- Creatinine clearance > 30 ml/min or Serum creatinine < 1.5xULN
3. Fasting serum cholesterol = 300 mg/dl or 7.75 mmol/L and fasting triglycerides = 2.5 ×ULN. In case one or both of these thresholds are exceeded, the patient can only be included after initiation of statin therapy or other lipid lowering drugs (eg fibrates), and when the above mentioned values have been achieved
4. Written informed consent obtained before any screening procedure and according to local applications.
5. Written informed consent for the analysis of germline DNA needed for translational analysis.
6. A new biopsy of tumor tissue with consent of the patient at the moment of progressive disease is preferable with the confirmation of hormone receptor positivity. If possible also frozen, for later translational investigations. In these patients 2 samples of 10 ml EDTA tubes should be taken to make germline DNA analysis possible. If a tumor biopsy is not possible at the baseline for this study due to lack of consent of the patient or for technical or safety reasons, an earlier biopsy should be available for subsequent biomarker analysis.
7. Adult women (> 18 years of age) with metastatic advanced breast cancer who relapse after adjuvant treatment treated with maximum of 3 lines of endocrine treatment.
8. For patients who present with metastatic disease at first diagnosis up to 4 lines of hormonal treatment before inclusion in the trial are accepted
9. Patients treated with maximum 1 line of chemotherapy for advanced disease.
10. Patient with histological or cytological confirmation of estrogen-receptor positive (ER+) or progesterone receptor positive (PR+) breast cancer
11. Patient with an ECOG Performance Status < 2
12. Patients who received prior sequential, but not necessary continuous Fulvestrant and exemestane plus everolimus treatment after progression disease
13. Measurable disease is not mandatory.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 40
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1.HER2-overexpressing patients by local laboratory testing (FISH positive).
2.Known hypersensitivity to mTOR inhibitors.
3.Currently receiving hormone replacement therapy.
4.Patients receiving concomitant immunosuppressive agents or chronic systemic corticosteroid use;
5.Patients with symptomatic visceral disease in need of urgent disease control: e.g. significant dyspnea related to pulmonary lymphangitic carcinomatosis or lung metastases or clinically meaningful symptomatic liver metastasis at the judgment of treating investigator.
6.Metastases estimated as more than a third of the liver as defined by sonogram and/or CT scan.
7. Symptomatic brain or other CNS metastases. Previously treated symptomatic brain metastases are allowed provided the patient is free of symptoms, prior radiotherapy for brain metastasis was more than four weeks before enrollment and the dose of corticosteroids is low and stable for at least two weeks prior to enrollment.
8. Patients with a known immunodeficiency disease.
9. Radiotherapy within four weeks prior to enrollment except in case of localized radiotherapy for analgesic purpose or for lytic lesions at risk of fracture which can then be completed within two weeks prior to enrollment. Patients must have recovered from radiotherapy toxicities prior to enrollment.
10. Patients with a known history of HIV seropositivity.
11. Active, bleeding diathesis, or on oral anti-vitamin K medication (except low dose warfarin and acetylsalicylic acid or equivalent, as long as the INR is = 2.0)
12. Any severe and / or uncontrolled medical conditions such as:
• Unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction =6 months prior to enrollment, serious uncontrolled cardiac arrhythmia
• Uncontrolled diabetes as defined by fasting serum glucose > 1.5 × ULN
• Acute and chronic, active infectious disorders and nonmalignant medical illnesses that are uncontrolled or whose control may be jeopardized by the complications of this study therapy
• Impairment of gastrointestinal function or gastrointestinal disease that may uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome)
• Significant symptomatic deterioration of lung function. If clinically indicated, pulmonary function tests including measures of predicted lung volumes, DLco, O2 saturation at rest on room air should be considered to exclude restrictive pulmonary disease, pneumonitis or pulmonary infiltrates.
13. Patients who test positive for hepatitis B or C. (Patients who test negative for HBV-DNA, HBsAg, and HBcAb but positive for HBsAb with prior history of vaccination against Hepatitis B will be eligible)
14. Patients being treated with drugs recognized as being strong inhibitors or inducers of the isoenzyme CYP3A (Rifabutin, Rifampicin, Clarithromycin, Ketoconazole, Itroconazole, Voriconazole, Ritinavir, Telithromycin) within the last 5 days prior to enrollment
15. History of non-compliance to medical regimens
16. Patients unwilling to or unable to comply with the protocol.
17. ECOG score >2
18. Diagnosis of concurrent malignancy within 5 years of study enrollment, except for an adequately treated cervical carcinoma in situ and a basal or squamous cell carcinoma of the skin.
19. Patients with more than one line of prior chemotherapy for advanced disease
20. Patients with more than 3 lines of endocrine treatment for metastatic disease who relapse after adjuvant treatment

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified