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

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

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.

Study Overview

• Status: Completed
• Conditions: Breast Cancer Metastatic
• Intervention / Treatment: Drug: Everolimus; Drug: Aromatase Inhibitors

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 Type: Interventional
• Enrollment (Actual): 110
• Phase: Phase 3

Contacts and Locations

Study Locations

• Italy
  • Mestre, Italy, 30174
    • Ospedale dell'Angelo
  • AN
    • Ancona, AN, Italy, 60020
      • Azienda Ospedaliero-Universitaria Ospedali Riuniti di Ancona
  • BO
    • Bologna, BO, Italy, 40138
      • Policlinico Sant'Orsola Malpighi
  • BR
    • Brindisi, BR, Italy, 72100
      • ASL Brindisi "Antonio Perrini"
  • BS
    • Brescia, BS, Italy, 25123
      • Azienda Spedali Civili di Brescia
  • Bg
    • Bergamo, Bg, Italy
      • Ospedale Papa Giovanni XXIII
  • CN
    • Cuneo, CN, Italy, 12100
      • A.S.O. S.Croce e Carle di Cuneo
  • CT
    • Catania, CT, Italy, 95123
      • Azienda Ospedaliero - Universitaria "Policlinico - Vittorio Emanuele"
  • FE
    • Cona, FE, Italy, 44124
      • Azienda Ospedaliero-Universitaria di Ferrara - Arcispedale Sant'Anna
  • GR
    • Grosseto, GR, Italy, 58100
      • Ospedale Misericordia di Grosseto
  • MI
    • Milano, MI, Italy, 20133
      • Istituto Nazionale dei Tumori IRCCS
  • PR
    • Parma, PR, Italy, 43126
      • Azienda Ospedaliera Universitaria di Parma
  • RE
    • Reggio Emilia, RE, Italy, 42123
      • IRCCS - Azienda Ospedaliera S.M. Nuova
  • TN
    • Trento, TN, Italy
      • Ospedale Civile Santa Chiara
  • UD
    • Udine, UD, Italy, 33100
      • Azienda Ospedaliero-Universitaria "Santa Maria della Misericordia"
  • VR
    • Negrar, VR, Italy, 37042
      • Ospedale Sacro Cuore - Don Calabria

Participation Criteria

Eligibility Criteria

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

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression free survival	PFS is defined as the time from randomization to the first documentation of objective disease progression or death from any cause	Up to 2 years after randomisation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival	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	Up to 2 years after randomisation
Response rate	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.	Every 12 weeks during treatment, up to 2 years after randomisation
Safety profile	Toxicity will be assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI -CTCAE), version 4.	Baseline and every 4 weeks during treatment, up to 2 years after randomisation

Collaborators and Investigators

• Sponsor: Istituto Oncologico Veneto IRCCS
• Collaborators: University of Padova
• Investigators: Principal Investigator: Pierfranco Conte, MD, PhD, Medical Oncology 2, Istituto Oncologico Veneto

Study record dates

Study Major Dates

• Study Start (Actual): July 30, 2014
• Primary Completion (Actual): February 28, 2020
• Study Completion (Actual): July 31, 2020

Study Registration Dates

• First Submitted: July 16, 2015
• First Submitted That Met QC Criteria: July 28, 2015
• First Posted (Estimate): July 30, 2015

Study Record Updates

• Last Update Posted (Actual): December 3, 2020
• Last Update Submitted That Met QC Criteria: December 2, 2020
• Last Verified: December 1, 2020

More Information

Terms related to this study

• Keywords: HER2 negative; Hormone receptor positive
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Hormone Antagonists; Steroid Synthesis Inhibitors; Estrogen Antagonists; Letrozole; Everolimus; Anastrozole; Exemestane; Aromatase Inhibitors
• Other Study ID Numbers: CRAD001JIT36T; 2013-004153-24 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No