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
Clinical Trial Information
Trial Contact: Jobson, Gillian S; Morales, Leticia; Pelley, Jennifer
IRB No: 17.082.07
Protocol Abbrev: MM-121-02-02-10
Principal Investigator: Regan Derek Rostorfer, MD
Sub Investigators: Baidas, Said MD; Cuesta, Ana MD; Moroose, Rebecca MD; Shah, Nikita MD
Phase: Drug: Phase II
Age Group: Adult
Secondary Protocol No: Merrimack
Applicable Disease Sites: Breast Cancer
Therapies Involved: Seribantumab
ClinicalTrials.gov ID: NCT03241810
The primary objective of this study is to determine whether the combination of seribantumab plus fulvestrant is more effective than placebo plus fulvestrant, based on investigator assessed Progression Free Survival (PFS) in HRG positive patients.
Histologically or cytologically confirmed ER+ and/or PR+ (with staining of > 1% cells) breast cancer
Confirmed postmenopausal status due to either surgical/natural menopause or ovarian suppression (initiated at least 28 days prior to Day 1 of Cycle 1) with a gonadotropin-releasing hormone (GnRH) agonist such as goserelin
HER2 negative per ASCO/CAP guidelines
A positive in-situ hybridization (ISH) test for heregulin with a score of ≥1+, as determined by centralized testing of unstained tumor tissue
Must have at least one lesion amenable to either core needle biopsy or fine needle aspiration
Progressed following at least one but no more than two prior systemic therapies in the locally advanced or metastatic disease setting
Received prior CDK inhibitor based therapy for locally advanced or metastatic disease Documented progression of locally advanced or metastatic disease as defined by RECIST v1.1. 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.
ECOG Performance Score (PS) of 0 or 1
Adequate bone marrow reserves as evidenced by:
• ANC > 1500/μl
• Platelet count > 100,000/μl; and
• Hemoglobin > 9 g/dL
Adequate hepatic function as evidenced by:
Serum total bilirubin ≤ 1.5 x ULN except for patients with Morbus Gilbert
Aspartate aminotransferase (AST), Alanine aminotransferase (ALT) and Alkaline Phosphatase ≤ 2.5 x ULN (≤ 5 x ULN is acceptable if liver metastases are present, and ≤ 5 x ULN of Alkaline Phosphatase is acceptable if bone metastases are present)
Adequate renal function as evidenced by a serum creatinine ≤ 1.5 x ULN
Recovered from clinically significant effects of any prior surgery, radiotherapy, or other antineoplastic therapy.
Patients may be treated with bone modifying agents such as bisphosphonates or receptor activator of nuclear factor kappa-B (RANK)-ligand agents (e.g. denosumab) per American Society of Clinical Oncology (ASCO) guidelines; whenever possible, patients requiring bone modifying agents should start treatment > 7 days prior to study therapy and should continue the same agent throughout study unless clinically compelled to change