A study to evaluate the efficacy and safety of of Enzalutamide with Trastuzumab in patients with HER2+ AR+ Metastatic or Locally Advanced Breast Cancer
- Conditions
- Subjects with HER2+ AR+ Metastatic or Locally Advanced Breast CancerMedDRA version: 17.0Level: PTClassification code 10065430Term: HER-2 positive breast cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 17.0Level: LLTClassification code 10027475Term: Metastatic breast cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 17.0Level: 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-ES
- Lead Sponsor
- Astellas Pharma Global Development, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Female
- Target Recruitment
- 80
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+ and ER- /PgR- breast cancer:
a) AR+ breast cancer 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.
b) ER-/PgR- breast cancer is defined as < 1% of tumor cells with nuclear ER/PgR staining by immunohistochemistry (IHC) or (for subjects with 1 - <10% tumor cells with nuclear
ER/PgR staining by IHC) the investigator would not treat with hormonal therapy (such as an aromatase inhibitor). Enrollment will be based on the local pathologist?s findings.
5. The subject has metastatic disease or has locally advanced disease that is not amendable to curative treatment.
6. The subject has measurable disease according to RECIST 1.1.
7. The subject has received at least 1 but no more than 4 lines of therapy in the metastatic or locally advanced disease (a line of therapy is defined as a course of treatment at the end of
which there was disease progression):
a) The subject has been documented to have progressed by investigator determination on a regimen containing an approved anti-HER2 agent (includes trastuzumab emtansine in
countries where it is not approved) as the most recent regimen. NOTE: Pertuzumab in the most recent regimen is exclusionary.
b) The subject progressed on a trastuzumab containing regimen for adjuvant (defined as progression >12 months after completing adjuvant treatment) or metastatic/ locally
advanced disease.
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:
a) Archival tissue from a primary tumor is preferred, but if the specimen is insufficient or unavailable, a core needle or incisional biopsy from a metastatic lesion is acceptable.
b) Cytological or fine-needle aspiration samples are not acceptable.
11. The subject has an estimated life expectancy of at least 6 months at Day 1, in the opinion of the Investigator.
12. The subject is either: Of non-childbearing potential: a) post-menopausal (defined as no spontaneous menses for at least 12 months pr
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:a)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.b)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: 1)absolute neutrophil count < 1.5 x109/L (< 1500 cells/mm3) 2)Platelet count < 75 x109/L (< 75,000 cells/mm3) 3) Hemoglobin < 5.6 mmol/L (< 9 g/dL) 4) Total bilirubin > 1.5 x Upper Limit of Normal (ULN) unless there is an alternate nonmalignant etiology (e.g., Gilbert?s syndrome). 5) Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 3 x ULN (or >5 xULN if hepatic metastasis is present).6)Creatinine > 1.5 x ULN. 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: a) Myocardial infarction within 6 months before the Day 1 visit. b) Uncontrolled angina within 6 months before the Day 1 visit. c) 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 or multi-gated acquisition scan performed within 3 months before the Day 1 visit reveals a left ventricular ejection fraction that is ? 50%. d)History of clinically significant ventricular arrhythmias (e.g., ventricular tachycardia, ventricular fibrillation, Torsade de Pointes).e) History of Mobitz II second degree or third degree heart block without a permanent pacemaker in place. f) Hypotension as indicated by systolic blood pressure < 86 mmHg on 2 consecutive measurements at the Screening visit. g) 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. h) 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 complications of advanced malignancy or requiring supplementary oxygen therapy.
10. The subject has an active gastrointestinal disorder affecting absorption (e.g., gastrectom
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To evaluate the efficacy of enzalutamide with trastuzumab in evaluable subjects with human epidermal growth factor receptor 2 positive (HER2+), androgen receptor positive (AR+) and estrogen receptor negative (ER-)/progesterone receptor negative (PgR-), metastatic or locally advanced breast cancer;Secondary Objective: To evaluate the following efficacy measures:<br>o Best Overall Response Rate (BORR)<br>o Overall Response Rate (ORR) at 24 weeks<br>o Progression Free Survival (PFS)<br>o Time to Progression (TTP)<br>o Duration of Response (DOR)<br>o Time to Response (TTR)<br>o To evaluate safety and tolerability.;Primary end point(s): CBR defined as the proportion of subjects with best objective response of CR, PR or SD at ? 24 weeks according to RECIST 1.1 criteria.;Timepoint(s) of evaluation of this end point: up to 2 years
- Secondary Outcome Measures
Name Time Method Secondary end point(s): Overall response rate (CR+PR) according to RECIST 1.1 criteria;Timepoint(s) of evaluation of this end point: up to 2 years