T-DM1+Pertuzumab in Pre-OP Early-Stage HER2+ BRCA
Purpose
This research study is studying a combination of drugs as a possible treatment for breast cancer that has tested positive for a protein called HER2. The names of the study interventions involved in this study are: - Trastuzumab emtansine (also called T-DM1) - Pertuzumab
Conditions
- HER-2 Positive Breast Cancer
- Breast Cancer
- Stage II Breast Cancer
- Stage III Breast Cancer
Eligibility
- Eligible Ages
- Over 18 Years
- Eligible Genders
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- Patients must have HER2-positive Stage II or III histologically confirmed invasive carcinoma of the breast. A minimum tumor size of 2 cm determined by physical exam or imaging is required. - HER-2 positive, confirmed by central testing (Clarient labs): IHC 3+ and/or FISH positive based on one of the three following criteria: - Single-probe average HER2 copy number≥6.0 signals/cell OR - Dual-probe HER2/CEP17 <2.0 with an average HER2 copy number ≥6.0 signals/cell OR - Dual-probe HER2/CEP17 ratio ≥2.0 - ER/PR determination is required. - Bilateral breast cancers are allowed if both cancers are HER2-positive. - Patients with multifocal or multicentric disease are eligible as long as one area meets eligibility criteria. - Breast imaging should include the ipsilateral axilla. For subjects with a clinically negative axilla, a sentinel lymph node biopsy will be performed either before or after preoperative therapy at the discretion of the subject's physicians. For subjects with a clinically positive axilla, a needle aspiration, core biopsy or SLN procedure will be performed to determine the presence of metastatic disease in the lymph nodes. - Men and women (with any menopausal status) ≥ 18 years of age - ECOG performance status 0 or 1 - Required laboratory values: - ANC ≥1500/mm3 - Hemoglobin ≥ 9 g/dl - Platelets ≥100,000/mm3 - Serum creatinine < 1.5 X ULN (institutional) - Total bilirubin ≤ 1.0 X ULN (institutional) For patients with Gilbert syndrome, the direct bilirubin should be within the institutional normal range. - AST and ALT ≤ 1.5x ULN (institutional) - Alkaline phosphatase ≤1.5x ULN (institutional) - Documentation of hepatitis B virus (HBV) and hepatitis C virus (HCV) serologies is required: this includes hepatitis B surface antigen (HBsAg) and/or total hepatitis B core antibody (HBcAb) in addition to HCV antibody testing. - Only for patients who test positive for hep B/C virus: PTT/INR < ULN (institutional) - Left ventricular ejection fraction (LVEF) ≥ 55% - Premenopausal women must have a negative serum pregnancy test, including women who have had a tubal ligation and for women less than 12 months after the onset of menopause. - Women of childbearing potential and men with partners of childbearing potential must be willing to use one highly effective form of non-hormonal contraception or two effective forms of non-hormonal contraception by the patient and/or partner and continue its use for the duration of the study treatment and for 7 months after the last dose of study treatment. - Potent CYP3A4 inhibitors, such as ketoconazole and erythromycin, should be avoided during the study treatment period with T-DM1. - Excessive alcohol intake should be avoided (occasional use is permitted). - Patients with a history of ipsilateral DCIS are eligible. - Patients undergoing breast conservation therapy (i.e. lumpectomy) must not have any contraindications to radiation therapy. - Willing and able to sign informed consent. - Willing to provide tissue for research purposes.
Exclusion Criteria
- Pregnant or nursing women due to the teratogenic potential of the study drugs. - Active, unresolved infection. - Receipt of intravenous antibiotics for infection within 7 days prior to enrollment. - Patients with active liver disease, for example, due to hepatitis B virus, hepatitis C virus, autoimmune hepatic disorder, or sclerosing cholangitis. - Uncontrolled hypertension (systolic >180 mm Hg and/or diastolic >100 mm Hg) or clinically significant (i.e. active) cardiovascular disease: cerebrovascular accident/stroke or myocardial infarction within 6 months prior to first study medication, unstable angina, congestive heart failure (CHF) of New York Heart Association (NYHA) Grade II or higher, or serious cardiac arrhythmia requiring medication. - Significant symptoms (Grade ≥2) peripheral neuropathy. - Other concurrent serious diseases that may interfere with planned treatment, including severe pulmonary conditions/illness, uncontrolled infections, uncontrolled diabetes. - Any prior treatment for the current breast cancer, including chemotherapy, hormonal therapy, radiation or experimental therapy.
Study Design
- Phase
- Phase 2
- Study Type
- Interventional
- Allocation
- N/A
- Intervention Model
- Single Group Assignment
- Primary Purpose
- Treatment
- Masking
- None (Open Label)
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Experimental T-DM1 and Pertuzumab |
T-DM1 3.6 mg per kg of body weight via IV every 3 weeks for 6 doses and Pertuzumab loading dose of 840 mg via IV on Cycle 1 Day 1 followed by maintenance dose of 420 mg via IV every 3 weeks for 6 doses. Excision of tumor/mastectomy of biopsy residual tumor within 42 days of the last cycle of therapy. |
|
More Details
- Status
- Active, not recruiting
- Sponsor
- Dana-Farber Cancer Institute
Study Contact
Detailed Description
This research study is a Phase II clinical trial. Phase II clinical trials test the safety and effectiveness of an investigational intervention to learn whether the intervention works in treating a specific disease. "Investigational" means that the intervention is being studied. The FDA (the U.S. Food and Drug Administration) has not approved T-DM1 for pre-operative use in breast cancer but it has been approved for other uses in breast cancer. The FDA has approved pertuzumab as a pre-operative treatment.