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

NCT03241810 | Terminated Phase 2 Results DMC FDA Drug

• 2 other identifiers: MM-121-02-02-102017-000565-76
• Study Type: interventional
• Target: 22
• Locations: 6 countries
• Sites: 59

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.

Conditions

Metastatic Breast Cancer

Keywords

Breast Cancer, HER2 Negative, Hormone receptor positive

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival

  Progression Free Survival is defined as the time from randomization to the first documented radiographical progression of disease using RECIST v1.1 or death from any cause, whichever comes first as assessed by the investigator. The tumor assessment (i.e., scan dates) was used for progression/censor date not the date corresponding to the determination of overall response. Progression-free survival time distribution and median survival for each treatment group were analyzed using the Kaplan-Meier method.

  Randomization until progression of disease or death due to any cause up to 13 months (The study terminated prematurely) . The primary analysis was planned to be initiated when 58 PFS events have occurred

Secondary Outcomes (6)

• Overall Survival

  Randomization until death due to any cause up to 13 months (The study terminated prematurely)

• Objective Response Rate

  Randomization through end of study up to 13 months (The study terminated prematurely)

• Time to Progression

  Randomization to date of objective tumor progression up to 13 months (The study terminated prematurely)

• Number of Participants With Treatment-emergent Adverse Events Reported With the Combinations of Seribantumab Plus Fulvestrant Versus Fulvestrant Alone

  TEAEs were collected through the study completion (30 Nov 2018), up to 13 months. Frequency and percent summaries were presented for TEAE defined as adverse events that occur or worsen in severity following the first dose of seribantumab, or fulvestrant

• Percentage of Treatment-emergent Adverse Events Reported With the Combinations of Seribantumab Plus Fulvestrant Versus Fulvestrant Alone

  TEAEs were collected through the study completion (30 Nov 2018), up to 13 months. Frequency and percent summaries were presented for TEAE defined as adverse events that occur or worsen in severity following the first dose of seribantumab, or fulvestrant

Study Arms (2)

Arm A

EXPERIMENTAL

Seribantumab Fulvestrant

Drug: Seribantumab; Drug: Fulvestrant

Arm B

ACTIVE COMPARATOR

Placebo Fulvestrant

Drug: Fulvestrant; Drug: Placebo

Interventions

Seribantumab DRUG

Seribantumab is a human monoclonal antibody that inhibits ErbB3 signalling

Also known as: MM-121

Arm A

Fulvestrant DRUG

Fulvestrant is an estrogen receptor antagonist with no agonist effects

Also known as: Faslodex

Arm A; Arm B

Placebo DRUG

Placebo

Also known as: Solution containing 20 mM histidine, 150 mM sodium chloride, at a pH of 6.5

Arm B

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: Confirmed postmenopausal status due to either surgical/natural menopause or ovarian suppression (initiated at least 28 days prior to Day 1 of Cycle 1).
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Patients must have histologically or cytologically confirmed ER+ and/or PR+ (with staining of \>1% cells) breast cancer.
• Patients with confirmed postmenopausal status due to either surgical/natural menopause or ovarian suppression.
• Patients must be HER2 negative.
• Patient must have at least one lesion amenable to either core needle biopsy or fine needle aspiration.
• Patient must have a positive in-situ hybridization (ISH) test for heregulin, as determined by centralized testing of unstained tumor tissue.
• Patients that have progressed following at least one but no more than two prior systemic therapies in the locally advanced or metastatic disease setting.
• 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).
• 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.
• Patients with adequate bone marrow reserves.
• Adequate hepatic function.
• Adequate renal function.
• Patient has recovered from clinically significant effects of any prior, surgery, radiosurgery, or other antineoplastic therapy.
• 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.

You may not qualify if:

• Prior treatment with an anti-ErbB3 antibody.
• Prior treatment with a chemotherapy in the locally advanced or metastatic disease setting.
• Patients cannot have received prior treatment with fulvestrant or other SERDs in the locally advanced or metastatic setting.
• Uncontrolled 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.
• 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.
• Known hypersensitivity to any of the components of seribantumab, fulvestrant, or who have had hypersensitivity reactions to fully human monoclonal antibodies.
• 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.

Sponsors & Collaborators

• Elevation Oncology: lead

Study Sites (59)

Ironwood Cancer and Research Centers- Chandler

Chandler, Arizona, 85224, United States

Location

Highland Oncology Group

Fayetteville, Arkansas, 72703, United States

Location

Beverly Hills Cancer Center

Beverly Hills, California, 90404-2131, United States

Location

Stanford University

Palo Alto, California, 94304, United States

Location

Saint Helena Hospital

St. Helena, California, 94574, United States

Location

Stamford Hospital

Stamford, Connecticut, 06902-3628, United States

Location

Sylvester Comprehensive Cancer Center

Miami, Florida, 33136, United States

Location

UF Health Cancer Center at Orlando Health

Orlando, Florida, 32806, United States

Location

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

Columbus Regional Research Institute

Columbus, Georgia, 31904, United States

Location

Cancer Care Specialists of Central Illinois

Decatur, Illinois, 62526, United States

Location

James M Stockman Cancer Institute

Frederick, Maryland, 21701, United States

Location

Holy Cross Hospital Health Center

Silver Spring, Maryland, 20902, United States

Location

Lahey Clinical Medical Center

Burlington, Massachusetts, 01805, United States

Location

University of Mississippi

Jackson, Mississippi, 39216, United States

Location

Mercy Hospital Springfield

Springfield, Missouri, 65804, United States

Location

Saint Francis Cancer Treatment Center

Grand Island, Nebraska, 68803, United States

Location

Dartmouth Hitchcock Medical Center

Lebanon, New Hampshire, 03756, United States

Location

Lineberger Comprehensive Cancer Center

Chapel Hill, North Carolina, 27599, United States

Location

Oncology Specialists of Charlotte

Charlotte, North Carolina, 28207, United States

Location

UPMC Cancer Center

Pittsburgh, Pennsylvania, 15232, United States

Location

University of Utah Health Care - Huntsman Cancer Institute

Salt Lake City, Utah, 84112, United States

Location

LKH - Universitätsklinikum Graz

Graz, 8036, Austria

Location

Universitaetsklinik fuer Gynaekologie und Geburtshilfe

Innsbruck, 6020, Austria

Location

Krankenhaus der Barmherzigen Schwestern Linz

Linz, 4010, Austria

Location

Medizinische Universität Wien

Vienna, 1090, Austria

Location

Clinique Saint-Pierre

Ottignies, Brabant Wallon, 1340, Belgium

Location

Centre Hospitalier de l'Ardenne - Clinique du Sein

Libramont, Luxembourg, 6800, Belgium

Location

Universitaire Ziekenhuis Leuven

Leuven, Vlaams Brabant, 3000, Belgium

Location

Universitair Ziekenhuis Antwerpen

Antwerp, 2650, Belgium

Location

Cliniques Universitaires Saint-Luc

Brussels, 1200, Belgium

Location

CHU UCL NAMUR - Sainte Elisabeth

Namur, 5000, Belgium

Location

University of Calgary

Calgary, Alberta, T2S 3C3, Canada

Location

British Columbia Cancer Agency

Kelowna, British Columbia, V1Y 5L3, Canada

Location

McGill University - Jewish General Hospital

Montreal, H3T 1E2, Canada

Location

Centre Hospitalier Affilie Universitaire de Quebec

Québec, G1S 4L8, Canada

Location

Universitätsklinikum Erlangen

Erlangen, Bavaria, 91054, Germany

Location

Medizinisches Zentrum Bonn Friedensplatz

Bonn, 53111, Germany

Location

Centrum fuer Haematologie und Onkologie Bethanien

Frankfurt, Germany

Location

Gynäkologisch-Onkologische Praxis Hannover

Hanover, 30177, Germany

Location

Rotkreuzklinikum München-Frauenklinik

Munich, 80637, Germany

Location

Klinikum Rechts der Isar der Technischen Universität München

München, 81675, Germany

Location

Onkologie Rheinsieg

Troisdorf, 53840, Germany

Location

Universitätsklinikum Ulm

Ulm, 89075, Germany

Location

Hospital Universitari General de Catalunya

Sant Cugat del Vallès, Barcelona, 08190, Spain

Location

Complejo Hospitalario Universitario La Coruña

A Coruña, 15006, Spain

Location

Hospital Teresa Herrera

A Coruña, 15006, Spain

Location

Hospital Universitari de Girona Doctor Josep Trueta

Girona, 17007, Spain

Location

Complejo Hospitalario de Jaén

Jaén, 23007, Spain

Location

Hospital Universitari Arnau de Vilanova

Lleida, 25198, Spain

Location

Hospital General Universitario Gregorio Marañón

Madrid, 28007, Spain

Location

Hospital Universitario Ramón Y Cajal

Madrid, 28034, Spain

Location

Hospital Clínico San Carlos

Madrid, 28040, Spain

Location

Hospital Universitario La Paz

Madrid, 28046, Spain

Location

Hospital Universitario Virgen de la Victoria

Málaga, 29010, Spain

Location

Hospital Son Llatzer

Palma de Mallorca, 07198, Spain

Location

De La Cruz Merino, Luis

Seville, 41009, Spain

Location

Hospital Clínico Universitario de Valencia

Valencia, 46010, Spain

Location

Hospital Universitario Miguel Servet

Zaragoza, 59009, Spain

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

seribantumab; Fulvestrant; Histidine; Sodium Chloride

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Estradiol; Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Essential; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Limitations and Caveats

Sponsor (Merrimack Pharmaceuticals, INC.) terminated the trial early due to business decision

Results Point of Contact

• Title: VP, Clinical Operations
• Organization: Elevation oncology

clinical@elevationoncology.com

+1-716 371 1125

Study Officials

• Marc Pipas, MD

  Merrimack Pharmaceuticals Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: This is a multi-center, randomized, double-blind, placebo-controlled Phase 2 Study.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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).

Study Record Dates

• First Submitted: August 2, 2017
• First Posted: August 8, 2017
• Study Start: August 15, 2017
• Primary Completion: November 30, 2018
• Study Completion: November 30, 2018
• Last Updated: September 2, 2020
• Results First Posted: September 2, 2020

Record last verified: 2019-11

Locations

US (22); CA (4); BE (6); AU (4); DE (8); ES (15)