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

NCT ID: NCT03241810

Last Updated: 2020-09-02

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 22 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-08-15
• Study Completion Date: 2018-11-30

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.

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.

Conditions

Metastatic Breast Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Arm A

Seribantumab

Fulvestrant

Group Type: EXPERIMENTAL

Seribantumab

Intervention Type: DRUG

Seribantumab is a human monoclonal antibody that inhibits ErbB3 signalling

Fulvestrant

Intervention Type: DRUG

Fulvestrant is an estrogen receptor antagonist with no agonist effects

Arm B

Placebo

Fulvestrant

Group Type: ACTIVE_COMPARATOR

Fulvestrant

Intervention Type: DRUG

Fulvestrant is an estrogen receptor antagonist with no agonist effects

Placebo

Intervention Type: DRUG

Placebo

Interventions

Seribantumab

Seribantumab is a human monoclonal antibody that inhibits ErbB3 signalling

Intervention Type: DRUG

Fulvestrant

Fulvestrant is an estrogen receptor antagonist with no agonist effects

Intervention Type: DRUG

Placebo

Placebo

Intervention Type: DRUG

Other Intervention Names

MM-121; Faslodex; Solution containing 20 mM histidine, 150 mM sodium chloride, at a pH of 6.5

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.

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Elevation Oncology

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Marc Pipas, MD

Role: STUDY_DIRECTOR

Merrimack Pharmaceuticals Inc.

Locations

Ironwood Cancer and Research Centers- Chandler

Chandler, Arizona, United States

Highland Oncology Group

Fayetteville, Arkansas, United States

Beverly Hills Cancer Center

Beverly Hills, California, United States

Stanford University

Palo Alto, California, United States

Saint Helena Hospital

St. Helena, California, United States

Stamford Hospital

Stamford, Connecticut, United States

Sylvester Comprehensive Cancer Center

Miami, Florida, United States

UF Health Cancer Center at Orlando Health

Orlando, Florida, United States

Moffitt Cancer Center

Tampa, Florida, United States

Columbus Regional Research Institute

Columbus, Georgia, United States

Cancer Care Specialists of Central Illinois

Decatur, Illinois, United States

James M Stockman Cancer Institute

Frederick, Maryland, United States

Holy Cross Hospital Health Center

Silver Spring, Maryland, United States

Lahey Clinical Medical Center

Burlington, Massachusetts, United States

University of Mississippi

Jackson, Mississippi, United States

Mercy Hospital Springfield

Springfield, Missouri, United States

Saint Francis Cancer Treatment Center

Grand Island, Nebraska, United States

Dartmouth Hitchcock Medical Center

Lebanon, New Hampshire, United States

Lineberger Comprehensive Cancer Center

Chapel Hill, North Carolina, United States

Oncology Specialists of Charlotte

Charlotte, North Carolina, United States

UPMC Cancer Center

Pittsburgh, Pennsylvania, United States

University of Utah Health Care - Huntsman Cancer Institute

Salt Lake City, Utah, United States

LKH - Universitätsklinikum Graz

Graz, , Austria

Universitaetsklinik fuer Gynaekologie und Geburtshilfe

Innsbruck, , Austria

Krankenhaus der Barmherzigen Schwestern Linz

Linz, , Austria

Medizinische Universität Wien

Vienna, , Austria

Clinique Saint-Pierre

Ottignies, Brabant Wallon, Belgium

Centre Hospitalier de l'Ardenne - Clinique du Sein

Libramont, Luxembourg, Belgium

Universitaire Ziekenhuis Leuven

Leuven, Vlaams Brabant, Belgium

Universitair Ziekenhuis Antwerpen

Antwerp, , Belgium

Cliniques Universitaires Saint-Luc

Brussels, , Belgium

CHU UCL NAMUR - Sainte Elisabeth

Namur, , Belgium

University of Calgary

Calgary, Alberta, Canada

British Columbia Cancer Agency

Kelowna, British Columbia, Canada

McGill University - Jewish General Hospital

Montreal, , Canada

Centre Hospitalier Affilie Universitaire de Quebec

Québec, , Canada

Universitätsklinikum Erlangen

Erlangen, Bavaria, Germany

Medizinisches Zentrum Bonn Friedensplatz

Bonn, , Germany

Centrum fuer Haematologie und Onkologie Bethanien

Frankfurt, , Germany

Gynäkologisch-Onkologische Praxis Hannover

Hanover, , Germany

Rotkreuzklinikum München-Frauenklinik

Munich, , Germany

Klinikum Rechts der Isar der Technischen Universität München

München, , Germany

Onkologie Rheinsieg

Troisdorf, , Germany

Universitätsklinikum Ulm

Ulm, , Germany

Hospital Universitari General de Catalunya

Sant Cugat del Vallès, Barcelona, Spain

Complejo Hospitalario Universitario La Coruña

A Coruña, , Spain

Hospital Teresa Herrera

A Coruña, , Spain

Hospital Universitari de Girona Doctor Josep Trueta

Girona, , Spain

Complejo Hospitalario de Jaén

Jaén, , Spain

Hospital Universitari Arnau de Vilanova

Lleida, , Spain

Hospital General Universitario Gregorio Marañón

Madrid, , Spain

Hospital Universitario Ramón Y Cajal

Madrid, , Spain

Hospital Clínico San Carlos

Madrid, , Spain

Hospital Universitario La Paz

Madrid, , Spain

Hospital Universitario Virgen de la Victoria

Málaga, , Spain

Hospital Son Llatzer

Palma de Mallorca, , Spain

De La Cruz Merino, Luis

Seville, , Spain

Hospital Clínico Universitario de Valencia

Valencia, , Spain

Hospital Universitario Miguel Servet

Zaragoza, , Spain

Countries

United States; Austria; Belgium; Canada; Germany; Spain

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2017-000565-76

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

MM-121-02-02-10

Identifier Type: -

Identifier Source: org_study_id