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

NCT ID: NCT02511639

Last Updated: 2020-12-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 110 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-07-30
• Study Completion Date: 2020-07-31

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

Conditions

Breast Cancer Metastatic

Keywords

Hormone receptor positive; HER2 negative

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm A: Everolimus & Aromatase inhibitors

Everolimus 10 mg po daily + Aromatase inhibitors (Exemestane 25 mg po daily or Letrozole 2.5 mg po daily or Anastrozole 1 mg po daily)

Group Type: EXPERIMENTAL

Everolimus

Intervention Type: DRUG

Everolimus is formulated as tablets of 10 mg strength for oral administration.

Aromatase Inhibitors

Intervention Type: DRUG

Anastrozole is formulated as tablets of 1 mg strength for oral administration. Letrozole is formulated as tablets of 2.5 mg strength for oral administration. Exemestane is formulated as tablets of 25 mg strength for oral administration.

Arm B: Aromatase inhibitors

Aromatase inhibitors (Exemestane 25 mg po daily or Letrozole 2.5 mg po daily or Anastrozole 1 mg po daily)

Group Type: ACTIVE_COMPARATOR

Aromatase Inhibitors

Intervention Type: DRUG

Anastrozole is formulated as tablets of 1 mg strength for oral administration. Letrozole is formulated as tablets of 2.5 mg strength for oral administration. Exemestane is formulated as tablets of 25 mg strength for oral administration.

Interventions

Everolimus

Everolimus is formulated as tablets of 10 mg strength for oral administration.

Intervention Type: DRUG

Aromatase Inhibitors

Anastrozole is formulated as tablets of 1 mg strength for oral administration. Letrozole is formulated as tablets of 2.5 mg strength for oral administration. Exemestane is formulated as tablets of 25 mg strength for oral administration.

Intervention Type: DRUG

Other Intervention Names

Exemestane; Letrozole; Anastrozole

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

University of Padova

OTHER

Sponsor Role: collaborator

Istituto Oncologico Veneto IRCCS

OTHER

Sponsor Role: lead

Responsible Party

Pierfranco Conte

MD, PhD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Pierfranco Conte, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Medical Oncology 2, Istituto Oncologico Veneto

Locations

Azienda Ospedaliero-Universitaria Ospedali Riuniti di Ancona

Ancona, AN, Italy

Ospedale Papa Giovanni XXIII

Bergamo, Bg, Italy

Policlinico Sant'Orsola Malpighi

Bologna, BO, Italy

ASL Brindisi "Antonio Perrini"

Brindisi, BR, Italy

Azienda Spedali Civili di Brescia

Brescia, BS, Italy

A.S.O. S.Croce e Carle di Cuneo

Cuneo, CN, Italy

Azienda Ospedaliero - Universitaria "Policlinico - Vittorio Emanuele"

Catania, CT, Italy

Azienda Ospedaliero-Universitaria di Ferrara - Arcispedale Sant'Anna

Cona, FE, Italy

Ospedale Misericordia di Grosseto

Grosseto, GR, Italy

Istituto Nazionale dei Tumori IRCCS

Milan, MI, Italy

Azienda Ospedaliera Universitaria di Parma

Parma, PR, Italy

IRCCS - Azienda Ospedaliera S.M. Nuova

Reggio Emilia, RE, Italy

Ospedale Civile Santa Chiara

Trento, TN, Italy

Azienda Ospedaliero-Universitaria "Santa Maria della Misericordia"

Udine, UD, Italy

Ospedale Sacro Cuore - Don Calabria

Negrar, VR, Italy

Ospedale dell'Angelo

Mestre, , Italy

Countries

Italy

Other Identifiers

2013-004153-24

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CRAD001JIT36T

Identifier Type: -

Identifier Source: org_study_id