Phase 2 Trial of Seribantumab Plus Fulvestrant in Postmenopausal Women With Metastatic Breast Cancer
Condition: Metastatic Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: Seribantumab; Fulvestrant; Placebo
Intervention description: Seribantumab is a human monoclonal antibody that inhibits ErbB3 signalling; Fulvestrant is an estrogen receptor antagonist with no agonist effects; Placebo
Intervention MeSH terms: Fulvestrant
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Patients will be randomized in a 1:1 ratio (experimental arm versus active comparator arm) using an Interactive Web Response System (IWRS). Randomization will be stratified based on bone-only disease (yes, no) and geographic region (US, non-US).
Masking: Triple (Participant, Care Provider, Investigator)
Masking description: This is a multi-center, randomized, double-blind, placebo-controlled Phase 2 Study.
Enrollment: 22.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Breast Cancer, HER2 Negative, Hormone receptor positive

Summary:

      This study is a multi-center, randomized, double-blind, placebo-controlled, Phase 2 study in
      postmenopausal women with heregulin positive, hormone receptor positive, HER2 negative
      metastatic, unresectable breast cancer.
    

Eligibility criteria:

        Inclusion Criteria:

        To be eligible for participation in the study, patients must meet the following criteria.
        Patients who are HRG negative do not need to complete screening procedures beyond HRG
        assessment.

          1. Patients must have histologically or cytologically confirmed ER+ and/or PR+ (with
             staining of >1% cells) breast cancer.

          2. Patients with confirmed postmenopausal status due to either surgical/natural menopause
             or ovarian suppression.

          3. Patients must be HER2 negative.

          4. Patient must have at least one lesion amenable to either core needle biopsy or fine
             needle aspiration.

          5. Patient must have a positive in-situ hybridization (ISH) test for heregulin, as
             determined by centralized testing of unstained tumor tissue.

          6. Patients that have progressed following at least one but no more than two prior
             systemic therapies in the locally advanced or metastatic disease setting.

          7. Patients with documented progression of locally advanced or metastatic disease as
             defined by RECISTv1.1 (Exception: patients with bone-only metastatic disease are
             eligible if they have at least 2 lytic lesions visible on a CT or MRI and have
             documented disease progression on prior therapy based on the appearance of new
             lesions).

          8. Patients with bone-only lesions who have received radiation to those lesions must have
             documented progression following radiation therapy.

          9. ECOG Performance Score (PS) of 0 or 1.

         10. Patients with adequate bone marrow reserves.

         11. Adequate hepatic function.

         12. Adequate renal function.

         13. Patient has recovered from clinically significant effects of any prior, surgery,
             radiosurgery, or other antineoplastic therapy.

         14. Patients who have experienced a venous thromboembolic event within 60 days of signing
             the main consent form should have been treated with anti-coagulants for at least 7
             days prior to beginning treatment and for the duration of treatment on this study.

        Exclusion Criteria:

        Patients must meet all the inclusion criteria listed above and none of the following
        exclusion criteria.

          1. Prior treatment with an anti-ErbB3 antibody.

          2. Prior treatment with a chemotherapy in the locally advanced or metastatic disease
             setting.

          3. Patients cannot have received prior treatment with fulvestrant or other SERDs in the
             locally advanced or metastatic setting.

          4. Uncontrolled CNS disease or presence of leptomeningeal disease.

          5. Inflammatory breast cancer.

          6. History of another active malignancy that required systemic therapy in the last 2
             years. Patients with prior history of in-situ cancer, basal, or squamous cell skin
             cancer are eligible.

          7. Patients with an active infection, or unexplained fever > 38.5 C during screening
             visits or on the first scheduled day of dosing, which in the investigator's opinion
             might compromise the patients participation in the trial or affect the study outcome.
             At the discretion of the investigator, patients with tumor fever may be enrolled.

          8. Known hypersensitivity to any of the components of seribantumab, fulvestrant, or who
             have had hypersensitivity reactions to fully human monoclonal antibodies.

          9. NYHA Class III or IV congestive heart failure.

         10. Patients with a significant history of cardiac disease (i.e. uncontrolled blood
             pressure, unstable angina, myocardial infarction within 1 year or ventricular
             arrhythmias requiring medication) are also excluded.

         11. Uncontrolled infection requiring IV antibiotics, antivirals, or antifungals; or active
             human immunodeficiency virus (HIV) infection, active hepatitis B infection or active
             hepatitis C infection.