A Phase II Trial of Ridaforolimus and Exemestane, Compared to Ridaforolimus, Dalotuzumab and Exemestane in Participants With Breast Cancer (MK-8669-064)
Condition: Breast Neoplasms
MeSH terms: Breast Neoplasms
Intervention: Ridaforolimus; Dalotuzumab; Exemestane
Intervention description: Ridaforolimus 10 mg tablet, administered PO at a dose of 10 mg (triplet) or 30 mg (doublet) depending upon randomization, on Days 1-5, 8-12, 15-19, & 22-26 of 28-day cycle.; Dalotuzumab administered 10 mg/kg IV weekly on Days 1, 8, 15, and 22 of 28-day cycle.; Exemestane 25 mg tablet administered PO QD.
Intervention MeSH terms: Exemestane
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 80.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The purpose of the study is to evaluate the efficacy of the triplet of ridaforolimus,
      dalotuzumab and exemestane compared to the combination of ridaforolimus and exemestane in
      post-menopausal participants with breast cancer. The primary hypothesis of the study is that
      the triplet of ridaforolimus, dalotuzumab and exemestane will improve progression free
      survival (PFS) compared to ridaforolimus and exemestane.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Females with a histologically confirmed diagnosis of breast cancer that is metastatic
             or locally advanced (locally advanced tumors must not be amenable to

        surgery or radiation therapy with curative intent) with the following pathological
        characteristics determined locally: estrogen receptor positive and Human Epidermal Growth
        Factor Receptor 2 (HER-2) negative, and Ki67 (a tumor marker) ≥ 15% determined by the
        central study laboratory

          -  Post-menopausal

          -  With advanced breast cancer whose disease was refractory to previous letrozole or
             anastrozole

          -  Has at least one confirmed measurable metastatic lesion

          -  Has a performance status ≤ 1 on the Eastern Cooperative Oncology Group (ECOG)
             performance scale

          -  Has a life expectancy of at least 3 months

          -  Adequate organ function

        Exclusion Criteria:

          -  Is receiving any other concurrent systemic tumor therapy, including

        hormonal agents and HER-2 inhibitors

          -  Previously received rapamycin or rapamycin analogs, including

        ridaforolimus, temsirolimus, or everolimus

          -  Received prior treatment with Insulin-like Growth Factor 1 Receptor (IGF-1R)
             inhibitors, Phosphatidylinositol 3-Kinase (PI3K) inhibitors, or

        other experimental agents that target PI3K, Protein Kinase B (AKT), or Mammalian Target of
        Rapamycin (mTOR) pathway

          -  Is receiving chronic corticosteroids administered at doses greater than

        those used for normal replacement therapy

          -  Has active brain metastasis or leptomeningeal carcinomatosis; patients

        with adequately treated brain metastases are eligible if they meet certain criteria

          -  Known allergy to macrolide antibiotics

          -  Has an active infection requiring antibiotics

          -  Significant or uncontrolled cardiovascular disease

          -  Poorly controlled Type 1 or 2 diabetes

          -  Is known to be Human Immunodeficiency Virus (HIV) positive

          -  Has a known history of active hepatitis B or C. Healthy carriers of hepatitis B are
             not allowed on this study