Phase 2 Trial of Seribantumab Plus Fulvestrant in Postmenopausal Women With Metastatic Breast Cancer
- Conditions
- Metastatic Breast Cancer
- Interventions
- Registration Number
- NCT03241810
- Lead Sponsor
- Elevation Oncology
- 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.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- Female
- Target Recruitment
- 22
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.
Patients must meet all the inclusion criteria listed above and none of the following exclusion criteria.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm A Seribantumab Seribantumab Fulvestrant Arm B Fulvestrant Placebo Fulvestrant Arm B Placebo Placebo Fulvestrant Arm A Fulvestrant Seribantumab Fulvestrant
- Primary Outcome Measures
Name Time Method Progression Free Survival 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 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.
- Secondary Outcome Measures
Name Time Method 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 Treatment-emergent adverse events (TEAEs) are defined as any event that occurred after the first dose of study drug and was not present prior to study drug administration or worsened in severity after study drug administration.
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 Treatment-emergent adverse events (TEAEs) are defined as any event that occurred after the first dose of study drug and was not present prior to study drug administration or worsened in severity after study drug administration.
Time to Progression Randomization to date of objective tumor progression up to 13 months (The study terminated prematurely) Time to Progression (TTP) is defined as the time from the date of randomization to the date of objective tumor progression.
Overall Survival Randomization until death due to any cause up to 13 months (The study terminated prematurely) Overall Survival (OS) is defined as the time from the date of randomization to the date of death from any cause. The study was terminated on 30 Nov 2018 . Data represents outcomes up to 150 days of treatment.
Objective Response Rate Randomization through end of study up to 13 months (The study terminated prematurely) Objective Response Rate (ORR) is defined as the proportion of patients with a RECIST v1.1 response recorded from randomization until disease progression characterized as either a Complete Response (CR) or Partial Response (PR) relative to the total number of evaluable patients.
Pharmacokinetic (PK) Profile of Seribantumab When Given in Combination With Fulvestrant and of Fulvestrant When Given in Combination With Serbantumab. 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 Pharmacokinetic (PK) evaluation are 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) is presented and calculated usig Non-compartmental analysis (NCA). Serum levels of MM-121 are measured at a central lab using an enzyme-linked immunosorbent assay (ELISA).
Trial Locations
- Locations (59)
Stamford Hospital
🇺🇸Stamford, Connecticut, United States
University of Mississippi
🇺🇸Jackson, Mississippi, United States
University of Utah Health Care - Huntsman Cancer Institute
🇺🇸Salt Lake City, Utah, United States
LKH - Universitätsklinikum Graz
🇦🇹Graz, Austria
Medizinische Universität Wien
🇦🇹Wien, Austria
Universitaetsklinik fuer Gynaekologie und Geburtshilfe
🇦🇹Innsbruck, Austria
Centre Hospitalier de l'Ardenne - Clinique du Sein
🇧🇪Libramont, Luxembourg, Belgium
Mercy Hospital Springfield
🇺🇸Springfield, Missouri, United States
British Columbia Cancer Agency
🇨🇦Kelowna, British Columbia, Canada
Ironwood Cancer and Research Centers- Chandler
🇺🇸Chandler, Arizona, United States
Beverly Hills Cancer Center
🇺🇸Beverly Hills, California, United States
Hospital ClÃnico San Carlos
🇪🇸Madrid, Spain
Krankenhaus der Barmherzigen Schwestern Linz
🇦🇹Linz, Austria
Hospital Son Llatzer
🇪🇸Palma de Mallorca, Spain
De La Cruz Merino, Luis
🇪🇸Sevilla, Spain
Hospital Universitari de Girona Doctor Josep Trueta
🇪🇸Gerona, Spain
Hospital Universitario La Paz
🇪🇸Madrid, Spain
Hospital ClÃnico Universitario de Valencia
🇪🇸Valencia, Spain
Hospital Universitario Virgen de la Victoria
🇪🇸Málaga, Spain
Rotkreuzklinikum München-Frauenklinik
🇩🇪Munich, Germany
Klinikum Rechts der Isar der Technischen Universität München
🇩🇪München, Germany
Stanford University
🇺🇸Palo Alto, California, United States
Saint Helena Hospital
🇺🇸Saint Helena, California, 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
Saint Francis Cancer Treatment Center
🇺🇸Grand Island, Nebraska, United States
Clinique Saint-Pierre
🇧🇪Ottignies, Brabant Wallon, Belgium
Universitair Ziekenhuis Antwerpen
🇧🇪Antwerp, Belgium
Universitaire Ziekenhuis Leuven
🇧🇪Leuven, Vlaams Brabant, Belgium
CHU UCL NAMUR - Sainte Elisabeth
🇧🇪Namur, Belgium
Centre Hospitalier Affilie Universitaire de Quebec
🇨🇦Quebec, Canada
McGill University - Jewish General Hospital
🇨🇦Montreal, Canada
University of Calgary
🇨🇦Calgary, Alberta, Canada
Centrum fuer Haematologie und Onkologie Bethanien
🇩🇪Frankfurt, Germany
Gynäkologisch-Onkologische Praxis Hannover
🇩🇪Hannover, Germany
Onkologie Rheinsieg
🇩🇪Troisdorf, Germany
Universitätsklinikum Ulm
🇩🇪Ulm, Germany
Hospital Teresa Herrera
🇪🇸A Coruña, Spain
Complejo Hospitalario Universitario La Coruña
🇪🇸La Coruña, Spain
Hospital General Universitario Gregorio Marañón
🇪🇸Madrid, Spain
Hospital Universitario Miguel Servet
🇪🇸Zaragoza, Spain
Dartmouth Hitchcock Medical Center
🇺🇸Lebanon, New Hampshire, United States
Sylvester Comprehensive Cancer Center
🇺🇸Miami, Florida, United States
Hospital Universitario Ramón Y Cajal
🇪🇸Madrid, Spain
Highland Oncology Group
🇺🇸Fayetteville, Arkansas, United States
Oncology Specialists of Charlotte
🇺🇸Charlotte, North Carolina, United States
Universitätsklinikum Erlangen
🇩🇪Erlangen, Bayern, Germany
UPMC Cancer Center
🇺🇸Pittsburgh, Pennsylvania, United States
Hospital Universitari General de Catalunya
🇪🇸Sant Cugat Del Vallès, Barcelona, Spain
Medizinisches Zentrum Bonn Friedensplatz
🇩🇪Bonn, Germany
Complejo Hospitalario de Jaén
🇪🇸Jaén, Spain
Hospital Universitari Arnau de Vilanova
🇪🇸Lleida, Spain
Cliniques Universitaires Saint-Luc
🇧🇪Brussels, Belgium
Moffitt Cancer Center
🇺🇸Tampa, Florida, United States
UF Health Cancer Center at Orlando Health
🇺🇸Orlando, Florida, United States
Lineberger Comprehensive Cancer Center
🇺🇸Chapel Hill, North Carolina, United States