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

Sponsor
Istituto Oncologico Veneto IRCCS (Other)
Overall Status
Completed
CT.gov ID
NCT02511639
Collaborator
University of Padova (Other)
110
Enrollment
16
Locations
2
Arms
72
Actual Duration (Months)
6.9
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

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
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
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 :
Jul 30, 2014
Actual Primary Completion Date :
Feb 28, 2020
Actual Study Completion Date :
Jul 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 [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 [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 [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 [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

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    Female
    Accepts Healthy Volunteers:
    No
    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.

    1. 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)

    2. 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

    3. History of non-compliance to medical regimens

    4. Patients unwilling to or unable to comply with the protocol

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Azienda Ospedaliero-Universitaria Ospedali Riuniti di Ancona Ancona AN Italy 60020
    2 Ospedale Papa Giovanni XXIII Bergamo Bg Italy
    3 Policlinico Sant'Orsola Malpighi Bologna BO Italy 40138
    4 ASL Brindisi "Antonio Perrini" Brindisi BR Italy 72100
    5 Azienda Spedali Civili di Brescia Brescia BS Italy 25123
    6 A.S.O. S.Croce e Carle di Cuneo Cuneo CN Italy 12100
    7 Azienda Ospedaliero - Universitaria "Policlinico - Vittorio Emanuele" Catania CT Italy 95123
    8 Azienda Ospedaliero-Universitaria di Ferrara - Arcispedale Sant'Anna Cona FE Italy 44124
    9 Ospedale Misericordia di Grosseto Grosseto GR Italy 58100
    10 Istituto Nazionale dei Tumori IRCCS Milano MI Italy 20133
    11 Azienda Ospedaliera Universitaria di Parma Parma PR Italy 43126
    12 IRCCS - Azienda Ospedaliera S.M. Nuova Reggio Emilia RE Italy 42123
    13 Ospedale Civile Santa Chiara Trento TN Italy
    14 Azienda Ospedaliero-Universitaria "Santa Maria della Misericordia" Udine UD Italy 33100
    15 Ospedale Sacro Cuore - Don Calabria Negrar VR Italy 37042
    16 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

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Pierfranco Conte, MD, PhD, Istituto Oncologico Veneto IRCCS
    ClinicalTrials.gov Identifier:
    NCT02511639
    Other Study ID Numbers:
    • CRAD001JIT36T
    • 2013-004153-24
    First Posted:
    Jul 30, 2015
    Last Update Posted:
    Dec 3, 2020
    Last Verified:
    Dec 1, 2020
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Keywords provided by Pierfranco Conte, MD, PhD, Istituto Oncologico Veneto IRCCS
    Hormone receptor positive
    HER2 negative
    Additional relevant MeSH terms:
    Breast Neoplasms
    Everolimus
    Letrozole
    Anastrozole
    Exemestane
    Aromatase Inhibitors

    Study Results

    No Results Posted as of Dec 3, 2020