Clinical Trials /

Phase 2 Trial of Seribantumab Plus Fulvestrant in Postmenopausal Women With Metastatic Breast Cancer

NCT03241810

Description:

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.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Phase 2 Trial of Seribantumab Plus Fulvestrant in Postmenopausal Women With Metastatic Breast Cancer
  • Official 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

Clinical Trial IDs

  • ORG STUDY ID: MM-121-02-02-10
  • SECONDARY ID: 2017-000565-76
  • NCT ID: NCT03241810

Conditions

  • Metastatic Breast Cancer

Interventions

DrugSynonymsArms
SeribantumabMM-121Arm A
FulvestrantFaslodexArm A
PlaceboArm B

Purpose

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.

Detailed Description

      This study is a randomized, double-blind, placebo-controlled international phase 2 trial in
      patients with HRG+, HR+, HER2- metastatic breast cancer that has progressed following
      treatment with no more than 2 prior therapies, one of which must have been a CDK inhibitor.
      All patients will be screened for heregulin using central testing, and eligible patients will
      be randomized to receive either seribantumab + fulvestrant or placebo + fulvestrant. Disease
      status will be assessed according to RECIST v 1.1 to support the primary endpoint.
    

Trial Arms

NameTypeDescriptionInterventions
Arm AExperimentalSeribantumab Fulvestrant
  • Seribantumab
  • Fulvestrant
Arm BActive ComparatorPlacebo Fulvestrant
  • Fulvestrant
  • Placebo

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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression Free Survival
Time Frame:A total study duration of approximately 20 months is expected. The primary analysis will be initiated when 58 PFS events have occurred
Safety Issue:
Description:Time from randomization to disease progression according to RECIST v 1.1 as assessed by the Investigator

Secondary Outcome Measures

Measure:Overall Survival
Time Frame:A total study duration of approximately 20 months is expected.
Safety Issue:
Description:Time from randomization to death
Measure:Objective Response Rate
Time Frame:A total study duration of approximately 20 months is expected.
Safety Issue:
Description:Based on RECIST v 1.1
Measure:Time to Progression
Time Frame:A total study duration of approximately 20 months is expected.
Safety Issue:
Description:
Measure:Rate of treatment-emergent adverse events reported with the combinations of seribantumab plus fulvestrant versus fulvestrant alone
Time Frame:A total study duration of approximately 20 months is expected.
Safety Issue:
Description:
Measure:Pharmacokinetic (PK) profile of seribantumab when given in combination with fulvestrant and of fulvestrant when given in combination with serbantumab.
Time Frame:A total study duration of approximately 20 months is expected.
Safety Issue:
Description:Pharmacokinetic (PK) evaluation will be performed on samples obtained pre-dose on day 1 and 15 of each 28-day cycle to assess pre-treatment trough concentrations of MM-121. The maximum observed concentration (Cmax) will be presented and will be calculated usig Non-compartmental analysis (NCA). Serum levels of MM-121 will be measured at a central lab using an enzyme-linked immunosorbent assay (ELISA).

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Merrimack Pharmaceuticals

Trial Keywords

  • Breast Cancer, HER2 Negative, Hormone receptor positive, heregulin

Last Updated

October 10, 2017