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
Overview
- Phase
- Phase 2
- Intervention
- Enzalutamide
- Conditions
- HER2 Amplified
- Sponsor
- Astellas Pharma Global Development, Inc.
- Enrollment
- 103
- Locations
- 39
- Primary Endpoint
- Clinical Benefit Rate (CBR)
- Status
- Completed
- Last Updated
- last year
Overview
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.
Investigators
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.
- •(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
- •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).
Arms & Interventions
Enzalutamide + Trastuzumab
Participants received 160 mg enzalutamide orally once daily and 6 mg/kg trastuzumab administered by intravenous infusion or subcutaneous injection every 21 days. Participants continued on treatment until disease progression, unacceptable toxicity or any other discontinuation criteria were met.
Intervention: Enzalutamide
Enzalutamide + Trastuzumab
Participants received 160 mg enzalutamide orally once daily and 6 mg/kg trastuzumab administered by intravenous infusion or subcutaneous injection every 21 days. Participants continued on treatment until disease progression, unacceptable toxicity or any other discontinuation criteria were met.
Intervention: Trastuzumab
Outcomes
Primary Outcomes
Clinical Benefit Rate (CBR)
Time Frame: 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.
Clinical benefit rate was defined as the percentage of evaluable participants with best objective response of confirmed complete response or partial response per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, or prolonged stable disease (≥ 24 weeks). Complete response (CR) was defined as the disappearance of all target and non-target lesions and no new lesions, and lymph nodes all \< 10 mm in short axis. Partial response (PR) was defined as disappearance of target lesions or a ≥ 30% decrease in the size of target lesions, with persistence of non-target lesions and no new lesions. Stable disease (SD) was defined as \< 30% decrease and \< 20% increase in the size of target lesions, persistence of non-target lesions, and no new lesions. PR and CR required confirmation with equivalent or improved assessment no less than 4 weeks after the date that PR or CR was first observed. SD required confirmation with equivalent or improved assessment no less than 8 weeks after enrollment.
Secondary Outcomes
- Overall Response Rate at Week 24(24 weeks)
- Best Overall Response Rate(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.)
- Progression-free Survival(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.)
- Time to Progression(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.)
- Duration of Response(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..)
- Time to Response(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.)
- Number of Participants With Treatment Emergent Adverse Events (TEAEs)(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))