Subjects with HER2+ AR+ Metastatic or Locally Advanced Breast Cancer MedDRA version: 20.0 Level: PT Classification code 10065430 Term: HER-2 positive breast cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 20.0 Level: LLT Classification code 10027475 Term: Metastatic breast cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 20.0 Level: LLT Classificat
Conditions
Interventions
Trade Name: Xtandi
Pharmaceutical Form: Capsule, soft
INN or Proposed INN: ENZALUTAMIDE
CAS Number: 915087-33-1
Current Sponsor code: MDV3100
Other descriptive name: Enzalutamide
Concentration unit: m
Sponsors
Astellas Pharma Global Development, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. The subject has consented and signed an Institutional Review Board (IRB)/Independent Ethics Committee (IEC) approved written Informed Consent and privacy language as per national regulations (e.g., Health Insurance Portability and Accountability Act [HIPAA] for U.S. sites) prior to any study-related procedures (including withdrawal of prohibited medication, if applicable). 2. The subject is a female = 18 years of age. 3. The subject has histologically or cytologically proven adenocarcinoma of the breast that is HER2+ defined as a score of 3+ for staining by immunohistochemistry (IHC), or IHC 2+ with HER2 gene amplification as determined by a locally approved in situ hybridization (ISH) assay, or (for patients without IHC data) HER2 gene amplification. 4. The subject has AR+ breast cancer, which is defined as any tumor cells with nuclear AR staining by immunohistochemistry (IHC). Enrollment may be based on the local pathologist's findings; however, tissue will be sent to a central pathology laboratory for assessment. NOTE: If a subject is enrolled in the study based on local pathologist results, but subsequent central assessment cannot confirm AR+ disease, the subject may remain in the study. 5. The subject has metastatic disease or has locally advanced disease that is not amendable to curative treatment. 6. 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). 7. The subject has received at least 1 line of therapy in the metastatic or locally advanced disease setting: -A line of therapy is defined as a course of treatment at the end of which there was disease progression, toxicity, or in the investigator's opinion, maximum benefit has been achieved. If the subject discontinued therapy due to any other reason but progressed without receiving other treatment, this would be considered a line of therapy. -The subject has been documented to have progressed by determination of the investigator on a regimen containing an anti-HER2 agent (includes trastuzumab emtansine in countries where it is not approved) as the most recent regimen or the most recent anti-HER2 regimen was discontinued for any toxicity, with the exception of a cardiotoxicity. - Subjects who received <28 days of therapy in the most recent regimen may be eligible upon approval from the medical monitor. - The subject progressed on a trastuzumab containing regimen. If progression occurred within 12 months after completing trastuzumabcontaining adjuvant treatment, this counts as having received trastuzumab but not as a line of therapy. 8. The subject has adequately recovered from toxicities due to prior therapy. 9. The subject has an Eastern Cooperative Oncology Group (ECOG) performance status < 1 at Screening and Day 1. 10. 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: - Archival tissue from the most recent biopsy available is preferred. - For subjects who are known AR+ per local pathology report, a fresh biopsy can be done per investigator discretion, to obtain tissue for central AR confirmation if the archival specimen is insufficient or unavailable.
Exclusion criteria
Exclusion criteria: 1. The subject has a severe concurrent disease, infection, or comorbidity that, in the judgment of the Investigator, would make the subject inappropriate for enrollment. 2. 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. 3. 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 in the opinion of the Investigator 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. 4. The subject has inadequate marrow, hepatic, and/or renal function at the Screening Visit defined as: ? Absolute neutrophil count 1.5 x Upper Limit of Normal (ULN) unless there is an alternate nonmalignant etiology (e.g., Gilbert's syndrome). ? Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 3 x ULN (or >5 xULN if hepatic metastasis is present). ? Creatinine > 1.5 x ULN or Glomerular Filtration Rate (eGFR)/Creatinine Clearance (CrCL) 170 mmHg or diastolic blood pressure > 105 mmHg on 2 consecutive measurements at the Screening visit. 9. The subject has significant respiratory disease, including severe dyspnea at rest due to
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy of enzalutamide with trastuzumab in evaluable subjects with human epidermal growth factor receptor 2 positive (HER2+), and androgen receptor positive (AR+), metastatic or locally advanced breast cancer, as measured by Clinical Benefit Rate (CBR) (defined as the proportion of evaluable subjects with best objective response of confirmed CR or PR per RECIST 1.1, or prolonged SD (= 24 weeks).;Secondary Objective: To evaluate the following efficacy measures: o Best Overall Response Rate (BORR) o Overall Response Rate (ORR) at 24 weeks o Progression Free Survival (PFS) o Time to Progression (TTP) o Duration of Response (DOR) o Time to Response (TTR) o To evaluate safety and tolerability.;Primary end point(s): CBR defined as the proportion of evaluable subjects with best objective response of confirmed CR or PR per RECIST 1.1 criteria, or prolonged SD ( = 24 weeks).;Timepoint(s) of evaluation of this end point: up to 2 years | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Overall response rate (CR+PR) at 24 weeks according to RECIST 1.1 criteria ;Timepoint(s) of evaluation of this end point: up to 2 years | — |
Countries
Belgium, Canada, Italy, Spain, United Kingdom, United States
Contacts
Public ContactService Desk - Global Clinical Dev.
Astellas Pharma Europe B.V.
Outcome results
None listed