Hormone receptor-positive advanced metastatic breast cancer in postmenopausal patients who have progressed on anastrozole or letrozole.
Conditions
Interventions
Trade Name: Afinitor
Product Name: N/A
Product Code: N/A
Pharmaceutical Form: Tablet
INN or Proposed INN: everolimus
CAS Number: 159351-69-6
Other descriptive name: EVEROLIMUS
Concentration unit: mg m
Sponsors
VU University Medical Center
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Adult women (= 18 years of age) with metastatic or locally advanced breast cancer not amenable to curative treatment by surgery or radiotherapy. 2. Histological or cytological confirmation of estrogen-receptor positive (ER+) breast cancer 3. Postmenopausal women. Postmenopausal status is defined either by: - Age = 55 years and one year or more of amenorrhea - Age =65 years) yes F.1.3.1 Number of subjects for this age range 87
Exclusion criteria
Exclusion criteria: 1. HER2-overexpressing patients by local laboratory testing (IHC 3+ staining or in situ hybridization positive). 2. Previous treatment mTOR inhibitors. 3. 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. 4. Currently receiving hormone replacement therapy, unless discontinued prior to enrollment. 5. Patients receiving concomitant immunosuppressive agents or chronic corticosteroids use, at the time of study entry except in cases outlined below: - Topical applications (e.g. rash), inhaled sprays (e.g. obstructive airways diseases), eye drops or local injections (e.g. intra-articular) are allowed. - Patients on stable low dose of corticosteroids for at least two weeks before enrollment are allowed in case of treatment of brain metastases. 6. Bilateral diffuse lymphangitic carcinomatosis or metastasis of the lung as the only manifestation of disease (>50% of lung involvement). 7. Evidence of metastases estimated as more than a third of the liver as defined by sonogram and/or CT scan. 8. Patients with a known history of HIV seropositivity. 9. 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) 10. 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 (except for hepatitis B and C positive patients) 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 significantly alter the absorption of study drugs (e.g., ulcerative disease, 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. 11. 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 – see also 1.4) 12. 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 13. History of non-compliance to medical regimens 14. Patients unwilling to or unable to comply with the protocol
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 1. compare progression-free survival on the combination of everolimus and exemestane between patients whose metastatic tumor expresses markers of PI3K pathway activation versus patients whose metastatic tumor does not express PI3K pathway activation. 2. immunohistochemistry on activated members of the PI3K pathway in primary tumor tissue of patients treated with everolimus and exemestane and compare the findings with the outcome of treatment and more specifically, with the results from other side-studies. 3. associate protein expression/ phosphorylation by proteomics in tumor biopsies to cancer mutations, PI3K pathway activation and progression-free survival on the exemestane and everolimus combination. 4. establish the incidence of mutations in PIK3CA and AKT in peripheral blood of advanced breast cancer patients amenable for treatment with everolimus and exemestane and to explore whether the presence of such mutations is associated with outcome to treatment in these patients. ;Secondary Objective: N/A;Primary end point(s): Progression Biomarker ;Timepoint(s) of evaluation of this end point: Preferably on a 4-weekly basis patients should be seen and data should be collected in the patient’s file which is standard GCP. All patients must be followed for 28 days after the last dose of everolimus for safety assessment and SAEs that might be related to everolimus should be reported. Radiological assessment of target and non-target lesions will be repeated preferable on a 12-weekly basis with the use of tests similar to those used at baseline. A bone scan should not be repeated earlier than 6 months. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): N/A;Timepoint(s) of evaluation of this end point: N/A | — |
Countries
Netherlands
Contacts
Public ContactProf. Dr. Epie Boven
VU University Medical Center
Outcome results
None listed