Clinical trial NCT02091960: A Study to Assess the Efficacy and Safety of Enzalutamide With Trastuzumab in Patients With Human Epidermal Growth Factor Receptor 2 Positive (HER2+), Androgen Receptor Positive (AR+) Metastatic or Locally Advanced Breast Cancer
Official title: A Phase 2, Multicenter, Open-label Study to Assess the Efficacy and Safety of Enzalutamide With Trastuzumab in Subjects With HER2+ AR+ Metastatic or Locally Advanced Breast Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: HER2 Amplified
Advanced Breast Cancer
Human Epidermal Growth Factor Receptor 2 (HER2)
Keywords: Enzalutamide
Trastuzumab
Breast cancer
HER2
Androgen receptor positive
Xtandi
Lead sponsor: Astellas Pharma Inc
Sponsor class: INDUSTRY
Collaborators: name: Medivation LLC, a wholly owned subsidiary of Pfizer Inc.
First posted: 2014-03-19
Enrollment: 103
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study was to evaluate the efficacy of enzalutamide with trastuzumab in patients with HER2+ AR+ metastatic or locally advanced breast cancer.


Eligibility criteria: Inclusion Criteria:

* The subject has histologically or cytologically proven adenocarcinoma of the breast that is HER2+
* The subject has AR+ breast cancer
* The subject has metastatic disease or has locally advanced disease that is not amendable to curative treatment
* The subject has measurable disease or nonmeasurable, evaluable disease per RECIST 1.1. (NOTE: pleural effusions, ascites or other third fluid space are not evaluable diseases per RECIST 1.1).
* The subject has received at least 1 line of therapy in the metastatic or locally advanced disease setting. The subject has been documented to have progressed by determination of the investigator on a regimen containing an anti-HER2 agent as the most recent regimen or the most recent anti-HER2 regimen was discontinued for any toxicity, with the exception of a cardiotoxicity.
* The subject has adequately recovered from toxicities due to prior therapy.
* The subject has an Eastern Cooperative Oncology Group performance (ECOG) status ≤ 1 at Screening and Day 1
* The subject has available at the site a representative, formalin-fixed, paraffin-embedded, tumor specimen that enabled the definitive diagnosis of breast cancer with adequate viable tumor cells in a tissue block (preferred) or ≥ 10 (20 preferred) freshly cut, unstained, serial slides and the associated pathology report

Exclusion Criteria:

* The subject has a severe concurrent disease, infection, or comorbidity that would make the subject inappropriate for enrollment.
* The subject has current or previously treated brain metastasis or active leptomeningeal disease. Brain imaging is required during screening in all subjects to exclude the presence of unequivocal central nervous system disease.
* The subject has a history of a non-breast cancer malignancy with the following exceptions:

  * The subject with a previous history of a non-invasive carcinoma is eligible if he/she has had successful curative treatment any time prior to Screening.
  * For all other malignancies, the subject is eligible if they have undergone potentially curative therapy and they have been considered disease free for at least 5 years prior to Screening.
* The subject has a history of seizure or any condition that may predispose to seizure (e.g., prior cortical stroke, significant brain trauma).
* The subject has a history of loss of consciousness, cerebrovascular accident, or transient ischemic attack within 12 months before the Day 1 visit.
* The subject has had a hypoglycemic episode requiring medical intervention while on insulin (or other anti-diabetic) treatment within 12 months before Day 1.
* The subject had a major surgical procedure, substantial open biopsy, or significant traumatic experience within 28 days before the Day 1 visit, or anticipation of need for major surgical procedure during the course of the study.
* The subject has had palliative radiation therapy to bone metastases within 14 days prior to the Day 1 visit (side effects from radiation must be resolved).
* The subject has received chemotherapy, immunotherapy, or any other systemic anticancer therapy, with the exception of anti-HER2 therapy (e.g., trastuzumab), within 14 days prior to the Day 1 visit.

Primary outcomes:
measure: Clinical Benefit Rate (CBR)
timeFrame: Tumor assessments were performed every 8 weeks through week 49, and then every 12 weeks thereafter until disease progression or death; the median duration of treatment was 70 days, and the maximum was 660 days.
Secondary outcomes:
measure: Overall Response Rate at Week 24
timeFrame: 24 weeks
measure: Best Overall Response Rate
timeFrame: Tumor assessments were performed every 8 weeks through week 49, and then every 12 weeks thereafter until disease progression or death; the median duration of treatment was 70 days, and the maximum was 660 days.
measure: Progression-free Survival
timeFrame: From the date of first dose of study drug until disease progression or death; the median duration of treatment was 70 days, and the maximum was 660 days.
measure: Time to Progression
timeFrame: From the date of first dose of study drug until disease progression or death; the median duration of treatment was 70 days, and the maximum was 660 days.
measure: Duration of Response
timeFrame: Tumor assessments were performed every 8 weeks through week 49, and then every 12 weeks thereafter until disease progression or death; the median duration of treatment was 70 days, and the maximum was 660 days..
measure: Time to Response
timeFrame: From the date of first dose of study drug until disease progression or death; the median duration of treatment was 70 days, and the maximum was 660 days.
measure: Number of Participants With Treatment Emergent Adverse Events (TEAEs)
timeFrame: From the first dose date of study drug to 30 days after the last dose date of study drug or the start of subsequent treatment or date of death, whichever was first (Up to 3031 days)
Other outcomes:
Locations:
city: Anaheim
country: United States
facility: Site US10051
state: California
city: Los Angeles
country: United States
facility: Site US10028
state: California
city: San Francisco
country: United States
facility: Site US10035
state: California
city: Fort Myers
country: United States
facility: Site US10079
state: Florida
city: Gainesville
country: United States
facility: Site US10074
state: Florida
city: Chicago
country: United States
facility: Site US10081
state: Illinois
city: Indianapolis
country: United States
facility: Site US10004
state: Indiana
city: Boston
country: United States
facility: Site US10070
state: Massachusetts
city: Saint Louis
country: United States
facility: Site US10078
state: Missouri
city: Cincinnati
country: United States
facility: Site US10072
state: Ohio
city: Pittsburgh
country: United States
facility: Site US10048
state: Pennsylvania
city: Knoxville
country: United States
facility: Site US10029
state: Tennessee
city: Nashville
country: United States
facility: Site US10042
state: Tennessee
city: Nashville
country: United States
facility: Site US10077
state: Tennessee
city: Fort Worth
country: United States
facility: Site US10076
state: Texas
city: Houston
country: United States
facility: Site US10082
state: Texas
city: Edegem
country: Belgium
facility: Site BE32003
state: Antwerp
city: Brasschaat
country: Belgium
facility: Site BE32013
city: Bruxelles
country: Belgium
facility: Site BE32016
city: Charleroi
country: Belgium
facility: Site BE32001
city: Leuven
country: Belgium
facility: Site BE32009
city: Liege
country: Belgium
facility: Site BE32007
city: Ottawa
country: Canada
facility: Site CA15022
state: Ontario
city: Toronto
country: Canada
facility: Site CA15023
state: Ontario
city: Regina
country: Canada
facility: Site CA15028
state: Saskatchewan
city: Saskatoon
country: Canada
facility: Site CA15026
state: Saskatchewan
city: Quebec
country: Canada
facility: Site CA15001
city: Meldola
country: Italy
facility: Site IT39005
state: Forli
city: Lecce
country: Italy
facility: Site IT39008
city: Milano
country: Italy
facility: Site IT39002
city: Milan
country: Italy
facility: Site IT39003
city: Sondrio
country: Italy
facility: Site IT39001
city: Udine
country: Italy
facility: Site IT39021
city: Pozuelo de Alarcon
country: Spain
facility: Site ES34014
state: Madrid
city: Barcelona
country: Spain
facility: Site ES34010
city: Madrid
country: Spain
facility: Site ES34013
city: Edinburgh
country: United Kingdom
facility: Site GB44003
city: Manchester
country: United Kingdom
facility: Site GB44013
city: Nottingham
country: United Kingdom
facility: Site GB44001
Study officials:
affiliation: Astellas Pharma Global Development, Inc.
name: Executive Medical Director
role: STUDY_DIRECTOR
References:
citation: Wardley A, Cortes J, Provencher L, Miller K, Chien AJ, Rugo HS, Steinberg J, Sugg J, Tudor IC, Huizing M, Young R, Abramson V, Bose R, Hart L, Chan S, Cameron D, Wright GS, Graas MP, Neven P, Rocca A, Russo S, Krop IE. The efficacy and safety of enzalutamide with trastuzumab in patients with HER2+ and androgen receptor-positive metastatic or locally advanced breast cancer. Breast Cancer Res Treat. 2021 May;187(1):155-165. doi: 10.1007/s10549-021-06109-7. Epub 2021 Feb 16.