Clinical Trials /

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

NCT02511639

Description:

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.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: Maintenance Aromatase Inhibitors (AIs)+ Everolimus vs AIs in Hormone Receptor Positive Metastatic Breast Cancer Patients
  • 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

Clinical Trial IDs

  • ORG STUDY ID: CRAD001JIT36T
  • SECONDARY ID: 2013-004153-24
  • NCT ID: NCT02511639

Conditions

  • Breast Cancer Metastatic

Interventions

DrugSynonymsArms
EverolimusArm A: Everolimus & Aromatase inhibitors
Aromatase InhibitorsExemestane, Letrozole, AnastrozoleArm A: Everolimus & Aromatase inhibitors

Purpose

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
    

Trial Arms

NameTypeDescriptionInterventions
Arm A: Everolimus & Aromatase inhibitorsExperimentalEverolimus 10 mg po daily + Aromatase inhibitors (Exemestane 25 mg po daily or Letrozole 2.5 mg po daily or Anastrozole 1 mg po daily)
  • Everolimus
  • Aromatase Inhibitors
Arm B: Aromatase inhibitorsActive ComparatorAromatase inhibitors (Exemestane 25 mg po daily or Letrozole 2.5 mg po daily or Anastrozole 1 mg po daily)
  • Aromatase Inhibitors

Eligibility 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

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

Secondary Outcome Measures

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

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Istituto Oncologico Veneto IRCCS

Trial Keywords

  • Hormone receptor positive
  • HER2 negative

Last Updated

September 16, 2016