Study of MEDI-573 Plus Standard Endocrine Therapy for Women With Hormone-sensitive Metastatic Breast Cancer
Condition: Hormone-sensitive, HER-2 Negative Metastatic Breast Cancer
MeSH terms: Breast Neoplasms; Hypersensitivity
Intervention: MEDI-573; Aromatase Inhibitor
Intervention description: Intravenous infusion of MEDI-573 (10 or 30 or 45 mg/kg) will be administered on Day 1 of each 21-day cycle until unacceptable toxicity, documentation of disease progression, or withdrawal for other reasons.; Aromatase inhibitor of the investigator's choice (letrozole, anastrozole, or exemestane) will be provided orally once daily until unacceptable toxicity, documentation of disease progression, or withdrawal for other reasons.
Intervention MeSH terms: Aromatase Inhibitors
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 188.0
Sex: Female
Minimum age: 18 Years
Maximum age: 99 Years
Healthy volunteers: No
Keywords: MEDI-573, breast cancer, metastatic, aromatase inhibitor, anti-IGF

Summary:

      Study to evaluate the safety, tolerability, antitumor activity, and pharmacology of MEDI-573
      in combination with an aromatase inhibitor (AI) in adult subjects with HR+, HER2-negative
      MBC.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically-confirmed MBC not deemed amenable to curative surgery or curative
             radiation therapy

          -  Tumors are positive for ER, PgR, or both

          -  Tumors must be negative for HER2 (by FISH, CISH or IHC)

          -  Female gender and age ≥ 18 years at time of study entry

          -  Postmenopausal

          -  Karnofsky Performance Status ≥ 70

          -  Life expectancy of ≥ 6 months

        Exclusion Criteria:

          -  Subjects who received prior chemotherapy, hormonal therapy, immunotherapy or biologic
             therapy for advanced or metastatic disease with the following exceptions:

               -  Prior adjuvant therapy with an AI and/or tamoxifen is allowed, provided treatment
                  ended at least 2 weeks prior to the first dose of MEDI-573

               -  Prior neoadjuvant and/or adjuvant chemotherapy for breast cancer is allowed

          -  Extensive symptomatic visceral disease including hepatic involvement and pulmonary
             lymphangitic spread of tumor, or disease that is considered by the investigator to be
             rapidly progressing or life threatening (eg, subjects who are intended for
             chemotherapy)

          -  Active brain metastases with the exception of subject has been treated and are
             asymptomatic and there has been no evidence of CNS progression for at least 4 weeks of
             first dose of MEDI-573

          -  Evidence of ongoing spinal cord compression or leptomeningeal carcinomatosis

          -  Unresolved toxicities from prior therapy with the exception of alopecia that have not
             resolved to ≤ Grade 1 at the time of starting study treatment

          -  Previous treatment with agents that target the IGF receptor

          -  History of allergy or reaction attributed to compounds of chemical or biologic
             composition similar to those of MEDI-573 or AI

          -  History of another invasive malignancy within 5 years except for curatively resected
             nonmelanoma skin cancer or carcinoma in situ of the cervix

          -  Poorly controlled diabetes mellitus