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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 : Completed
First Posted : July 30, 2015
Last Update Posted : December 3, 2020
Sponsor:
Collaborator:
University of Padova
Information provided by (Responsible Party):
Pierfranco Conte, Istituto Oncologico Veneto IRCCS

Tracking Information
First Submitted Date  ICMJE July 16, 2015
First Posted Date  ICMJE July 30, 2015
Last Update Posted Date December 3, 2020
Actual Study Start Date  ICMJE July 30, 2014
Actual Primary Completion Date February 28, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 28, 2015)
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
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 28, 2015)
  • 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
  • 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.
  • 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.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Maintenance Aromatase Inhibitors (AIs)+ Everolimus vs AIs in Hormone Receptor Positive Metastatic Breast Cancer Patients
Official Title  ICMJE 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
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
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Breast Cancer Metastatic
Intervention  ICMJE
  • 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
Study Arms  ICMJE
  • 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)
    Interventions:
    • Drug: Everolimus
    • Drug: Aromatase Inhibitors
  • 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)
    Intervention: Drug: Aromatase Inhibitors
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: September 17, 2018)
110
Original Estimated Enrollment  ICMJE
 (submitted: July 28, 2015)
253
Actual Study Completion Date  ICMJE July 31, 2020
Actual Primary Completion Date February 28, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Italy
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02511639
Other Study ID Numbers  ICMJE CRAD001JIT36T
2013-004153-24 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Pierfranco Conte, Istituto Oncologico Veneto IRCCS
Study Sponsor  ICMJE Istituto Oncologico Veneto IRCCS
Collaborators  ICMJE University of Padova
Investigators  ICMJE
Principal Investigator: Pierfranco Conte, MD, PhD Medical Oncology 2, Istituto Oncologico Veneto
PRS Account Istituto Oncologico Veneto IRCCS
Verification Date December 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP