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

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ClinicalTrials.gov Identifier: NCT03241810
Recruitment Status : Recruiting
First Posted : August 8, 2017
Last Update Posted : July 6, 2018
Sponsor:
Information provided by (Responsible Party):
Merrimack Pharmaceuticals

Brief 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.

Condition or disease Intervention/treatment Phase
Metastatic Breast Cancer Drug: Seribantumab Drug: Fulvestrant Drug: Placebo Phase 2

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.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 80 participants
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.
Primary Purpose: Treatment
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
Actual Study Start Date : August 15, 2017
Estimated Primary Completion Date : April 2019
Estimated Study Completion Date : September 2020

Resource links provided by the National Library of Medicine

Drug Information available for: Fulvestrant

Arm Intervention/treatment
Experimental: Arm A

Seribantumab

Fulvestrant

Drug: Seribantumab
Seribantumab is a human monoclonal antibody that targets ErbB3, a cell surface receptor that is activated by the ligand heregulin. Heregulin-driven ErbB3 signaling has been implicated as a mechanism of tumor growth and resistance to targeted, cytotoxic and anti-endocrine therapies. When used in the combination setting, seribantumab is designed to block ErbB3 signaling in order to enhance the anti-tumor effect of a combination therapy partner.
Other Name: MM-121

Drug: Fulvestrant
Fulvestrant is a drug treatment of hormone receptor-positive metastatic breast cancer in post-menopausal women with disease progression following anti-estrogen therapy. It is an estrogen receptor antagonist with no agonist effects, which works both by down-regulating and by degrading the estrogen receptor.
Other Name: Faslodex

Active Comparator: Arm B

Placebo

Fulvestrant

Drug: Fulvestrant
Fulvestrant is a drug treatment of hormone receptor-positive metastatic breast cancer in post-menopausal women with disease progression following anti-estrogen therapy. It is an estrogen receptor antagonist with no agonist effects, which works both by down-regulating and by degrading the estrogen receptor.
Other Name: Faslodex

Drug: Placebo
Placebo




Primary Outcome Measures :
  1. 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 ]
    Time from randomization to disease progression according to RECIST v 1.1 as assessed by the Investigator


Secondary Outcome Measures :
  1. Overall Survival [ Time Frame: A total study duration of approximately 20 months is expected. ]
    Time from randomization to death

  2. Objective Response Rate [ Time Frame: A total study duration of approximately 20 months is expected. ]
    Based on RECIST v 1.1

  3. Time to Progression [ Time Frame: A total study duration of approximately 20 months is expected. ]
  4. 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. ]
  5. 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. ]
    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).



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Gender Based Eligibility:   Yes
Gender Eligibility Description:   Confirmed postmenopausal status due to either surgical/natural menopause or ovarian suppression (initiated at least 28 days prior to Day 1 of Cycle 1).
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03241810


Contacts
Contact: Tiffany Crowell 617-441-1000 tcrowell@merrimack.com
Contact: Marc Pipas, MD 617-441-1000 mpipas@merrimack.com

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Sponsors and Collaborators
Merrimack Pharmaceuticals

Responsible Party: Merrimack Pharmaceuticals
ClinicalTrials.gov Identifier: NCT03241810     History of Changes
Other Study ID Numbers: MM-121-02-02-10
2017-000565-76 ( EudraCT Number )
First Posted: August 8, 2017    Key Record Dates
Last Update Posted: July 6, 2018
Last Verified: July 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Merrimack Pharmaceuticals:
Breast Cancer, HER2 Negative, Hormone receptor positive, heregulin

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Hormones
Estradiol
Fulvestrant
Antibodies, Monoclonal
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Estrogen Receptor Antagonists
Estrogen Antagonists
Hormone Antagonists
Estrogens
Immunologic Factors