Clinical trial NCT02511639: Maintenance Aromatase Inhibitors (AIs)+ Everolimus vs AIs in Hormone Receptor Positive Metastatic Breast Cancer Patients
Official title: MAINtenance Afinitor: A Randomized Trial Comparing Maintenance Aromatase Inhibitors (AIs) + Everolimus (Afinitor) vs AIs in Hormone Receptor Positive (HR+) Metastatic Breast Cancer Patients With Disease Control After First Line Chemotherapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Breast Cancer Metastatic
Keywords: Hormone receptor positive
HER2 negative
Lead sponsor: Istituto Oncologico Veneto IRCCS
Sponsor class: OTHER
Collaborators: name: University of Padova
First posted: 2015-07-30
Enrollment: 110
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: 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.

Detailed description: The purpose of this study is:

* to compare the progression free survival (PFS) of AIs/everolimus to AIs administered as maintenance therapy in HR+ advanced breast cancer patients with disease control (Complete Response (CR), Partial Response (PR) or Stable Disease (SD))after 1st line chemotherapy.
* To evaluate the overall survival
* To assess the safety profile
* To evaluate the response rate

Eligibility 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

Primary outcomes:
measure: Progression free survival
timeFrame: Up to 2 years after randomisation
Secondary outcomes:
measure: Overall survival
timeFrame: Up to 2 years after randomisation
measure: Response rate
timeFrame: Every 12 weeks during treatment, up to 2 years after randomisation
measure: Safety profile
timeFrame: Baseline and every 4 weeks during treatment, up to 2 years after randomisation
Other outcomes:
Locations:
city: Ancona
country: Italy
facility: Azienda Ospedaliero-Universitaria Ospedali Riuniti di Ancona
state: AN
city: Bergamo
country: Italy
facility: Ospedale Papa Giovanni XXIII
state: Bg
city: Bologna
country: Italy
facility: Policlinico Sant'Orsola Malpighi
state: BO
city: Brindisi
country: Italy
facility: ASL Brindisi "Antonio Perrini"
state: BR
city: Brescia
country: Italy
facility: Azienda Spedali Civili di Brescia
state: BS
city: Cuneo
country: Italy
facility: A.S.O. S.Croce e Carle di Cuneo
state: CN
city: Catania
country: Italy
facility: Azienda Ospedaliero - Universitaria "Policlinico - Vittorio Emanuele"
state: CT
city: Cona
country: Italy
facility: Azienda Ospedaliero-Universitaria di Ferrara - Arcispedale Sant'Anna
state: FE
city: Grosseto
country: Italy
facility: Ospedale Misericordia di Grosseto
state: GR
city: Milano
country: Italy
facility: Istituto Nazionale dei Tumori IRCCS
state: MI
city: Parma
country: Italy
facility: Azienda Ospedaliera Universitaria di Parma
state: PR
city: Reggio Emilia
country: Italy
facility: IRCCS - Azienda Ospedaliera S.M. Nuova
state: RE
city: Trento
country: Italy
facility: Ospedale Civile Santa Chiara
state: TN
city: Udine
country: Italy
facility: Azienda Ospedaliero-Universitaria "Santa Maria della Misericordia"
state: UD
city: Negrar
country: Italy
facility: Ospedale Sacro Cuore - Don Calabria
state: VR
city: Mestre
country: Italy
facility: Ospedale dell'Angelo
Study officials:
affiliation: Medical Oncology 2, Istituto Oncologico Veneto
name: Pierfranco Conte, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: