Overview

Maintenance Aromatase Inhibitors (AIs)+ Everolimus vs AIs in Hormone Receptor Positive Metastatic Breast Cancer Patients

Status:
Completed
Trial end date:
2020-07-31
Target enrollment:
0
Participant gender:
Female
Summary
The purpose of this study is to compare maintenance Aromatase Inhibitors (AIs) + everolimus with Aromatase Inhibitors alone after 1st line chemotherapy in patients with HR+ metastatic breast cancer.
Phase:
Phase 3
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
Istituto Oncologico Veneto IRCCS
Collaborator:
University of Padova
Treatments:
Anastrozole
Aromatase Inhibitors
Everolimus
Exemestane
Hormones
Letrozole
Sirolimus
Criteria
Inclusion Criteria:

1. >18 years old women with metastatic breast cancer

2. Histological confirmation of hormone-receptor positive (defined as at least 10% of
estrogen receptor (ER) and/or progesterone receptor (PgR) positivity) and human
epidermal growth factor receptor 2 (HER2) negative (score 0-1+ in immunohistochemistry
or FISH negativity) breast cancer

3. Postmenopausal status

4. One line of chemotherapy for metastatic disease; patients must have received a minimum
of 6 cycles of chemotherapy in order to be eligible, and must have obtained disease
control (CR or PR od SD)

5. Eastern Cooperative Oncology Group (ECOG) Performance status < 2

6. Adequate bone marrow and coagulation function

7. Adequate liver function

8. Adequate renal function

9. Fasting serum cholesterol ≤ 300 mg/dl or 7.75 mmol/L and fasting triglycerides ≤ 2.5 ×
upper limit of normal (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

10. Fasting glucose < 1.5 × ULN

11. Written informed consent obtained before any screening procedure and according to
local guidelines.

Exclusion Criteria:

1. HER2-overexpressing patients by local laboratory testing (immunohistochemistry 3+
staining or in situ hybridization positive)

2. Previous treatment with mammalian target of rapamycin (mTOR) inhibitors

3. Known hypersensitivity to mTOR inhibitors, e.g. sirolimus (rapamycin)

4. More than one chemotherapy line for metastatic disease

5. Treatment with angiogenetic compounds as maintenance therapy (eg. bevacizumab)

6. 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

7. Symptomatic central nervous system metastases

8. Patients with a known history of HIV positivity

9. Active, bleeding diathesis, or on oral anti-vitamin K medication (except low dose
warfarin and acetylsalicylic acid or equivalent, as long as the international
normalized ratio (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 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, diffusion
capacity of lung for carbon monoxide (DLco) and 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
hepatitis B virus (HBV)-DNA, HBsAg, and HBcAb but positive for HBsAb with prior
history of vaccination against Hepatitis B will be eligible)

12. Patients being treated with drugs recognized as being strong inhibitors or inducers of
the isoenzyme Cytochrome P3A (Rifabutin, Rifampicin, Clarithromycin, Ketoconazole,
Itraconazole, Voriconazole, Ritonavir, 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