Clinical trial NCT03241810: Phase 2 Trial of Seribantumab Plus Fulvestrant in Postmenopausal Women With Metastatic Breast Cancer
Official title: Randomized Phase 2 Trial of Seribantumab Plus Fulvestrant in Postmenopausal Women With Hormone Receptor-positive, Heregulin Positive (HRG+), HER2 Negative Metastatic Breast Cancer (Merrimack Pharmaceuticals Inc.)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Metastatic Breast Cancer
Keywords: Breast Cancer, HER2 Negative, Hormone receptor positive
Lead sponsor: Elevation Oncology
Sponsor class: INDUSTRY
First posted: 2017-08-08
Enrollment: 22
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
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).
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Progression Free Survival
timeFrame: 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:
measure: Overall Survival
timeFrame: Randomization until death due to any cause up to 13 months (The study terminated prematurely)
measure: Objective Response Rate
timeFrame: Randomization through end of study up to 13 months (The study terminated prematurely)
measure: Time to Progression
timeFrame: Randomization to date of objective tumor progression up to 13 months (The study terminated prematurely)
measure: Number of Participants With Treatment-emergent Adverse Events Reported With the Combinations of Seribantumab Plus Fulvestrant Versus Fulvestrant Alone
timeFrame: 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
measure: Percentage of Treatment-emergent Adverse Events Reported With the Combinations of Seribantumab Plus Fulvestrant Versus Fulvestrant Alone
timeFrame: 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
measure: Pharmacokinetic (PK) Profile of Seribantumab When Given in Combination With Fulvestrant and of Fulvestrant When Given in Combination With Serbantumab.
timeFrame: The study terminated prematurely after 13 months. Were to be analyzed post-dose on Cycle 1,Week 1 & pre-dose for all subsequent seribantumab infusions until the completion of Cycle 2. Fulvestrant PK samples were to be collected prior to seribantumab dose
Other outcomes:
Locations:
city: Chandler
country: United States
facility: Ironwood Cancer and Research Centers- Chandler
state: Arizona
city: Fayetteville
country: United States
facility: Highland Oncology Group
state: Arkansas
city: Beverly Hills
country: United States
facility: Beverly Hills Cancer Center
state: California
city: Palo Alto
country: United States
facility: Stanford University
state: California
city: Saint Helena
country: United States
facility: Saint Helena Hospital
state: California
city: Stamford
country: United States
facility: Stamford Hospital
state: Connecticut
city: Miami
country: United States
facility: Sylvester Comprehensive Cancer Center
state: Florida
city: Orlando
country: United States
facility: UF Health Cancer Center at Orlando Health
state: Florida
city: Tampa
country: United States
facility: Moffitt Cancer Center
state: Florida
city: Columbus
country: United States
facility: Columbus Regional Research Institute
state: Georgia
city: Decatur
country: United States
facility: Cancer Care Specialists of Central Illinois
state: Illinois
city: Frederick
country: United States
facility: James M Stockman Cancer Institute
state: Maryland
city: Silver Spring
country: United States
facility: Holy Cross Hospital Health Center
state: Maryland
city: Burlington
country: United States
facility: Lahey Clinical Medical Center
state: Massachusetts
city: Jackson
country: United States
facility: University of Mississippi
state: Mississippi
city: Springfield
country: United States
facility: Mercy Hospital Springfield
state: Missouri
city: Grand Island
country: United States
facility: Saint Francis Cancer Treatment Center
state: Nebraska
city: Lebanon
country: United States
facility: Dartmouth Hitchcock Medical Center
state: New Hampshire
city: Chapel Hill
country: United States
facility: Lineberger Comprehensive Cancer Center
state: North Carolina
city: Charlotte
country: United States
facility: Oncology Specialists of Charlotte
state: North Carolina
city: Pittsburgh
country: United States
facility: UPMC Cancer Center
state: Pennsylvania
city: Salt Lake City
country: United States
facility: University of Utah Health Care - Huntsman Cancer Institute
state: Utah
city: Graz
country: Austria
facility: LKH - Universitätsklinikum Graz
city: Innsbruck
country: Austria
facility: Universitaetsklinik fuer Gynaekologie und Geburtshilfe
city: Linz
country: Austria
facility: Krankenhaus der Barmherzigen Schwestern Linz
city: Vienna
country: Austria
facility: Medizinische Universität Wien
city: Wien
country: Austria
facility: Medizinische Universität Wien
city: Ottignies
country: Belgium
facility: Clinique Saint-Pierre
state: Brabant Wallon
city: Libramont
country: Belgium
facility: Centre Hospitalier de l'Ardenne - Clinique du Sein
state: Luxembourg
city: Leuven
country: Belgium
facility: Universitaire Ziekenhuis Leuven
state: Vlaams Brabant
city: Antwerp
country: Belgium
facility: Universitair Ziekenhuis Antwerpen
city: Brussels
country: Belgium
facility: Cliniques Universitaires Saint-Luc
city: Namur
country: Belgium
facility: CHU UCL NAMUR - Sainte Elisabeth
city: Calgary
country: Canada
facility: University of Calgary
state: Alberta
city: Kelowna
country: Canada
facility: British Columbia Cancer Agency
state: British Columbia
city: Montreal
country: Canada
facility: McGill University - Jewish General Hospital
city: Quebec
country: Canada
facility: Centre Hospitalier Affilie Universitaire de Quebec
city: Erlangen
country: Germany
facility: Universitätsklinikum Erlangen
state: Bayern
city: Bonn
country: Germany
facility: Medizinisches Zentrum Bonn Friedensplatz
city: Frankfurt
country: Germany
facility: Centrum fuer Haematologie und Onkologie Bethanien
city: Hannover
country: Germany
facility: Gynäkologisch-Onkologische Praxis Hannover
city: Munich
country: Germany
facility: Rotkreuzklinikum München-Frauenklinik
city: München
country: Germany
facility: Klinikum Rechts der Isar der Technischen Universität München
city: Troisdorf
country: Germany
facility: Onkologie Rheinsieg
city: Ulm
country: Germany
facility: Universitätsklinikum Ulm
city: Sant Cugat Del Vallès
country: Spain
facility: Hospital Universitari General de Catalunya
state: Barcelona
city: A Coruña
country: Spain
facility: Hospital Teresa Herrera
city: Gerona
country: Spain
facility: Hospital Universitari de Girona Doctor Josep Trueta
city: Jaén
country: Spain
facility: Complejo Hospitalario de Jaén
city: La Coruña
country: Spain
facility: Complejo Hospitalario Universitario La Coruña
city: Lleida
country: Spain
facility: Hospital Universitari Arnau de Vilanova
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Marañón
city: Madrid
country: Spain
facility: Hospital Universitario Ramón Y Cajal
city: Madrid
country: Spain
facility: Hospital Clínico San Carlos
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Málaga
country: Spain
facility: Hospital Universitario Virgen de la Victoria
city: Palma de Mallorca
country: Spain
facility: Hospital Son Llatzer
city: Sevilla
country: Spain
facility: De La Cruz Merino, Luis
city: Valencia
country: Spain
facility: Hospital Clínico Universitario de Valencia
city: Zaragoza
country: Spain
facility: Hospital Universitario Miguel Servet
Study officials:
affiliation: Merrimack Pharmaceuticals Inc.
name: Marc Pipas, MD
role: STUDY_DIRECTOR
References: