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

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ClinicalTrials.gov Identifier: NCT02511639
Recruitment Status : Recruiting
First Posted : July 30, 2015
Last Update Posted : September 19, 2016
University of Padova
Information provided by (Responsible Party):
Pierfranco Conte, Istituto Oncologico Veneto IRCCS

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 Type : Interventional  (Clinical Trial)
Estimated Enrollment : 253 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
Study Start Date : July 2014
Estimated Primary Completion Date : February 2018
Estimated Study Completion Date : December 2018

Resource links provided by the National Library of Medicine

U.S. FDA Resources

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

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.

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
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.
  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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02511639

Contact: Gian Luca De Salvo, MD, PhD 00390498215710 gianluca.desalvo@ioveneto.it

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Ospedale G da Saliceto Not yet recruiting
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IRCCS - Azienda Ospedaliera S.M. Nuova Recruiting
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I.R.C.C.S. - Fondazione del Piemonte per l'Oncologia Recruiting
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Azienda Ospedaliero-Universitaria "Santa Maria della Misericordia" Not yet recruiting
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ULSS 6 Vicenza Not yet recruiting
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Ospedale Civile Maggiore - AOUI - Verona Recruiting
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Ospedale dell'Angelo Recruiting
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Sponsors and Collaborators
Istituto Oncologico Veneto IRCCS
University of Padova
Principal Investigator: Pierfranco Conte, MD, PhD Medical Oncology 2, Istituto Oncologico Veneto

Responsible Party: Pierfranco Conte, MD, PhD, Istituto Oncologico Veneto IRCCS
ClinicalTrials.gov Identifier: NCT02511639     History of Changes
Other Study ID Numbers: CRAD001JIT36T
2013-004153-24 ( EudraCT Number )
First Posted: July 30, 2015    Key Record Dates
Last Update Posted: September 19, 2016
Last Verified: September 2016

Keywords provided by Pierfranco Conte, Istituto Oncologico Veneto IRCCS:
Hormone receptor positive
HER2 negative

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Aromatase Inhibitors
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents
Immunosuppressive Agents
Immunologic Factors
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents
Steroid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Estrogen Antagonists
Hormone Antagonists
Antineoplastic Agents, Hormonal