Clinical Trial 19328

Cancer Type:
Interventions:Faslodex (fulvestrant); Not Applicable; Placebo; Seribantumab; fulvestrant

Study Type: Treatment
Phase of Study: Phase II
Investigators:

  • Heather Han

Overview

Study Title

SHERBOC: A Double-blind, Placebo-controlled, Phase 2 trial of Seribantumab Plus Fulvestrant in Postmenopausal Women with Hormone Receptor-positive, Heregulin Positive (HRG+), HER2 Negative Metastatic Breast Cancer Whose Disease Progressed After Prior Systemic Therapy

Summary

The main purpose of this study is to learn whether cancer cell growth (disease progression) is delayed in people taking seribantumab and fulvestrant for the treatment of heregulin positive, hormone receptor positive metastatic breast cancer.

Objective

Primary Objective: To determine whether the combination of seribantumab + fulvestrant is more effective than placebo + fulvestrant based on investigator assessed Progression Free Survival (PFS) in HRG positive patients (defined as HRG ISH score of > 1+). Secondary Objectives: To determine whether the combination of seribantumab + fulvestrant is more effective than placebo + fulvestrant in HRG positive patients for the following clinical outcome parameters: Time to Progression (TTP). Overall Survival (OS). Objective Response Rate (ORR) based on RECISTv1.1. To describe the safety profile of seribantumab in combination with fulvestrant. To characterize the pharmacokinetic (PK) profile of seribantumab when given in combination with fulvestrant and of fulvestrant when given in combination with seribantumab. Exploratory Objectives: To assess the correlation for HRG expression between fresh tissue biopsies and archival samples where available.

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.
  • Participants must have histologically or cytologically confirmed ER+ and/or PR+ (with staining of >1% cells) breast cancer.
  • Participants with confirmed postmenopausal status due to either surgical/natural menopause or ovarian suppression.
  • Must be HER2 negative.
  • Must have at least one lesion amenable to either core needle biopsy or fine needle aspiration.
  • Must have a positive in-situ hybridization (ISH) test for heregulin, as determined by centralized testing of unstained tumor tissue.
  • Have progressed following at least one but no more than two prior systemic therapies in the locally advanced or metastatic disease setting.
  • 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).
  • Patients with bone-only lesions who have received radiation to those lesions must have documented progression following radiation therapy.
  • Eastern Cooperative Oncology Group (ECOG) Performance Score (PS) of 0 or 1.
  • Adequate bone marrow reserves.
  • Adequate hepatic and renal function.
  • Have recovered from clinically significant effects of any prior, surgery, radiosurgery, or other antineoplastic therapy.
  • Potential participants 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

  • Prior treatment with an anti-ErbB3 antibody.
  • Prior treatment with a chemotherapy in the locally advanced or metastatic disease setting.
  • Cannot have received prior treatment with fulvestrant or other SERDs in the locally advanced or metastatic setting.
  • Uncontrolled central nervous system (CNS) disease or presence of leptomeningeal disease.
  • Inflammatory breast cancer.
  • 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.
  • 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.
  • Known hypersensitivity to any of the components of seribantumab, fulvestrant, or who have had hypersensitivity reactions to fully human monoclonal antibodies.
  • New York Heart Association (NYHA) Class III or IV congestive heart failure.
  • 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.
  • Uncontrolled infection requiring IV antibiotics, antivirals, or antifungals; or active human immunodeficiency virus (HIV) infection, active hepatitis B infection or active hepatitis C infection.