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

• ClinicalTrials.gov Identifier: NCT02511639
• Recruitment Status: Completed
• First Posted: July 30, 2015
• Last Update Posted: December 3, 2020
• Sponsor: Istituto Oncologico Veneto IRCCS
• Collaborator: University of Padova
• Information provided by (Responsible Party): Pierfranco Conte, Istituto Oncologico Veneto IRCCS

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Breast Cancer Metastatic	Drug: Everolimus; Drug: Aromatase Inhibitors	Phase 3

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

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 110 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: July 30, 2014
• Actual Primary Completion Date: February 28, 2020
• Actual Study Completion Date: July 31, 2020

Arms and Interventions

Arm	Intervention/treatment
Experimental: 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)	Drug: Everolimus; Everolimus is formulated as tablets of 10 mg strength for oral administration.; 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.; Other Names: Exemestane; Letrozole; Anastrozole
Active Comparator: Arm B: Aromatase inhibitors; Aromatase inhibitors (Exemestane 25 mg po daily or Letrozole 2.5 mg po daily or Anastrozole 1 mg po daily)	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.; Other Names: Exemestane; Letrozole; Anastrozole

Outcome Measures

Primary Outcome Measures :

1. Progression free survival [ Time Frame: Up to 2 years after randomisation ]
   PFS is defined as the time from randomization to the first documentation of objective disease progression or death from any cause

Secondary Outcome Measures :

1. Overall survival [ Time Frame: Up to 2 years after randomisation ]
   Overall survival is defined as the interval between the date of randomization and the date of patient death due to any cause, or the last date the patient was known to be alive
2. Response rate [ Time Frame: Every 12 weeks during treatment, up to 2 years after randomisation ]
   Responses will be assessed according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria only for patients with measurable disease at the time of study entry.
3. Safety profile [ Time Frame: Baseline and every 4 weeks during treatment, up to 2 years after randomisation ]
   Toxicity will be assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI -CTCAE), version 4.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

Italy

Azienda Ospedaliero-Universitaria Ospedali Riuniti di Ancona

Ancona, AN, Italy, 60020

Ospedale Papa Giovanni XXIII

Bergamo, Bg, Italy

Policlinico Sant'Orsola Malpighi

Bologna, BO, Italy, 40138

ASL Brindisi "Antonio Perrini"

Brindisi, BR, Italy, 72100

Azienda Spedali Civili di Brescia

Brescia, BS, Italy, 25123

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

Cuneo, CN, Italy, 12100

Azienda Ospedaliero - Universitaria "Policlinico - Vittorio Emanuele"

Catania, CT, Italy, 95123

Azienda Ospedaliero-Universitaria di Ferrara - Arcispedale Sant'Anna

Cona, FE, Italy, 44124

Ospedale Misericordia di Grosseto

Grosseto, GR, Italy, 58100

Istituto Nazionale dei Tumori IRCCS

Milano, MI, Italy, 20133

Azienda Ospedaliera Universitaria di Parma

Parma, PR, Italy, 43126

IRCCS - Azienda Ospedaliera S.M. Nuova

Reggio Emilia, RE, Italy, 42123

Ospedale Civile Santa Chiara

Trento, TN, Italy

Azienda Ospedaliero-Universitaria "Santa Maria della Misericordia"

Udine, UD, Italy, 33100

Ospedale Sacro Cuore - Don Calabria

Negrar, VR, Italy, 37042

Ospedale dell'Angelo

Mestre, Italy, 30174

Sponsors and Collaborators

Istituto Oncologico Veneto IRCCS

University of Padova

Investigators

• Principal Investigator: Pierfranco Conte, MD, PhD; Medical Oncology 2, Istituto Oncologico Veneto

More Information

• Responsible Party: Pierfranco Conte, MD, PhD, Istituto Oncologico Veneto IRCCS
• ClinicalTrials.gov Identifier: NCT02511639
• Other Study ID Numbers: CRAD001JIT36T; 2013-004153-24 ( EudraCT Number )
• First Posted: July 30, 2015
• Last Update Posted: December 3, 2020
• Last Verified: December 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

Keywords provided by Pierfranco Conte, Istituto Oncologico Veneto IRCCS:

Hormone receptor positive; HER2 negative

Additional relevant MeSH terms:

Breast Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Everolimus; Letrozole; Anastrozole; Exemestane; Aromatase Inhibitors; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Steroid Synthesis Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Estrogen Antagonists; Hormone Antagonists; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal