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

Metastatic Breast Cancer Clinical Trial

— SHERBOC  

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.)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03241810
• Other study ID #: MM-121-02-02-10
• Secondary ID: 2017-000565-76
• Status: Terminated
• Phase: Phase 2
• Start date: August 15, 2017
• Est. completion date: November 30, 2018

Study information

• Verified date: November 2019
• Source: Elevation Oncology
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Terminated
• Enrollment: 22
• Est. completion date: November 30, 2018
• Est. primary completion date: November 30, 2018
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Breast Neoplasms
• Metastatic Breast Cancer

Intervention

Drug:
• Seribantumab
Seribantumab is a human monoclonal antibody that inhibits ErbB3 signalling
• Fulvestrant
Fulvestrant is an estrogen receptor antagonist with no agonist effects
• Placebo
Placebo

Locations

Country	Name	City	State
Austria	LKH - Universitätsklinikum Graz	Graz
Austria	Universitaetsklinik fuer Gynaekologie und Geburtshilfe	Innsbruck
Austria	Krankenhaus der Barmherzigen Schwestern Linz	Linz
Austria	Medizinische Universität Wien	Vienna
Austria	Medizinische Universität Wien	Wien
Belgium	Universitair Ziekenhuis Antwerpen	Antwerp
Belgium	Cliniques Universitaires Saint-Luc	Brussels
Belgium	Universitaire Ziekenhuis Leuven	Leuven	Vlaams Brabant
Belgium	Centre Hospitalier de l'Ardenne - Clinique du Sein	Libramont	Luxembourg
Belgium	CHU UCL NAMUR - Sainte Elisabeth	Namur
Belgium	Clinique Saint-Pierre	Ottignies	Brabant Wallon
Canada	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	Quebec
Germany	Medizinisches Zentrum Bonn Friedensplatz	Bonn
Germany	Universitätsklinikum Erlangen	Erlangen	Bayern
Germany	Centrum fuer Haematologie und Onkologie Bethanien	Frankfurt
Germany	Gynäkologisch-Onkologische Praxis Hannover	Hannover
Germany	Klinikum Rechts der Isar der Technischen Universität München	München
Germany	Rotkreuzklinikum München-Frauenklinik	Munich
Germany	Onkologie Rheinsieg	Troisdorf
Germany	Universitätsklinikum Ulm	Ulm
Spain	Hospital Teresa Herrera	A Coruña
Spain	Hospital Universitari de Girona Doctor Josep Trueta	Gerona
Spain	Complejo Hospitalario de Jaén	Jaén
Spain	Complejo Hospitalario Universitario La Coruña	La Coruña
Spain	Hospital Universitari Arnau de Vilanova	Lleida
Spain	Hospital Clínico San Carlos	Madrid
Spain	Hospital General Universitario Gregorio Marañón	Madrid
Spain	Hospital Universitario La Paz	Madrid
Spain	Hospital Universitario Ramón Y Cajal	Madrid
Spain	Hospital Universitario Virgen de la Victoria	Málaga
Spain	Hospital Son Llatzer	Palma de Mallorca
Spain	Hospital Universitari General de Catalunya	Sant Cugat Del Vallès	Barcelona
Spain	De La Cruz Merino, Luis	Sevilla
Spain	Hospital Clínico Universitario de Valencia	Valencia
Spain	Hospital Universitario Miguel Servet	Zaragoza
United States	Beverly Hills Cancer Center	Beverly Hills	California
United States	Lahey Clinical Medical Center	Burlington	Massachusetts
United States	Ironwood Cancer and Research Centers- Chandler	Chandler	Arizona
United States	Lineberger Comprehensive Cancer Center	Chapel Hill	North Carolina
United States	Oncology Specialists of Charlotte	Charlotte	North Carolina
United States	Columbus Regional Research Institute	Columbus	Georgia
United States	Cancer Care Specialists of Central Illinois	Decatur	Illinois
United States	Highland Oncology Group	Fayetteville	Arkansas
United States	James M Stockman Cancer Institute	Frederick	Maryland
United States	Saint Francis Cancer Treatment Center	Grand Island	Nebraska
United States	University of Mississippi	Jackson	Mississippi
United States	Dartmouth Hitchcock Medical Center	Lebanon	New Hampshire
United States	Sylvester Comprehensive Cancer Center	Miami	Florida
United States	UF Health Cancer Center at Orlando Health	Orlando	Florida
United States	Stanford University	Palo Alto	California
United States	UPMC Cancer Center	Pittsburgh	Pennsylvania
United States	Saint Helena Hospital	Saint Helena	California
United States	University of Utah Health Care - Huntsman Cancer Institute	Salt Lake City	Utah
United States	Holy Cross Hospital Health Center	Silver Spring	Maryland
United States	Mercy Hospital Springfield	Springfield	Missouri
United States	Stamford Hospital	Stamford	Connecticut
United States	Moffitt Cancer Center	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Elevation Oncology

Countries where clinical trial is conducted

United States,  Austria,  Belgium,  Canada,  Germany,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Overall Survival	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.	Randomization until death due to any cause up to 13 months (The study terminated prematurely)
Secondary	Objective Response Rate	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.	Randomization through end of study up to 13 months (The study terminated prematurely)
Secondary	Time to Progression	Time to Progression (TTP) is defined as the time from the date of randomization to the date of objective tumor progression.	Randomization to date of objective tumor progression up to 13 months (The study terminated prematurely)
Secondary	Number of Participants With Treatment-emergent Adverse Events Reported With the Combinations of Seribantumab Plus Fulvestrant Versus Fulvestrant Alone	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.	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
Secondary	Percentage of Treatment-emergent Adverse Events Reported With the Combinations of Seribantumab Plus Fulvestrant Versus Fulvestrant Alone	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.	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
Secondary	Pharmacokinetic (PK) Profile of Seribantumab When Given in Combination With Fulvestrant and of Fulvestrant When Given in Combination With Serbantumab.	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).	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