A study to evaluate the efficacy and safety of of Enzalutamide with Trastuzumab in patients with HER2+ AR+ Metastatic or Locally Advanced Breast Cancer

Phase 1

• Conditions: Subjects with HER2+ AR+ Metastatic or Locally Advanced Breast Cancer; MedDRA version: 20.0Level: PTClassification code 10065430Term: HER-2 positive breast cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 20.0Level: LLTClassification code 10027475Term: Metastatic breast cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 20.0Level: LLTClassification code 10072740Term: Locally advanced breast cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2013-000093-29-BE
• Lead Sponsor: Astellas Pharma Global Development, Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2014-03-31
• Last Update Posted: 12 March 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Female
• Target Recruitment: 80

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

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 x109/L (< 1500 cells/mm3)
? Platelet count < 75 x109/L (< 75,000 cells/mm3)
? Hemoglobin < 5.6 mmol/L (< 9 g/dL)
? Total bilirubin > 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) < 30 mL/min, whichever is more restrictive.
? NOTE: May not have received any growth factors or blood transfusions within 7 days before the hematology values obtained at screening.
5. The subject has a history of seizure or any condition that may predispose to seizure (e.g., prior cortical stroke, significant brain trauma).
6. The subject has a history of loss of consciousness, cerebrovascular accident or transient ischemic attack within 12 months before the Day 1 visit.
7. The subject has had a hypoglycemic episode requiring medical intervention while on insulin (or other anti-diabetic) treatment within 12 months before Day 1.
8. The subject has clinically significant cardiovascular disease including:
? Myocardial infarction within 6 months before the Day 1 visit.
? Uncontrolled angina within 6 months before the Day 1 visit.
? Congestive heart failure New York Heart Association (NYHA) Class III or IV or history of congestive heart failure NYHA Class III or IV in the past, unless a screening echocardiogram, myocardial perfusion scintigraphy (MPS), or multi-gated acquisition scan performed within 3 months before the Day 1 visit reveals a left ventricular ejection fraction that is = 50%.
? History of clinically significant ventricular arrhythmias (e.g., ventricular tachycardia, ventricular fibrillation, Torsade de Pointes).
? History of Mobitz II second degree or third degree heart block without a permanent pacemaker in place.
? Hypotension as indicated by systolic blood pressure < 86 mmHg on 2 consecutive measurements at the Screening visit.
? Bradycardia (in the presence of known cardiovascular disease) as indicated by a heart rate of < 50 beats per minute on the Screening electrocardiogram (ECG) recording.
? Uncontrolled hypertension as indicated by systolic blood pressure > 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

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified