Johns Hopkins Kimmel Cancer Center in Baltimore
Sibley Memorial Hospital
This trial studies how well paclitaxel, trastuzumab, and pertuzumab work in eliminating further chemotherapy after surgery in patients with HER2-positive stage II-IIIa breast cancer who have no cancer remaining at surgery (either in the breast or underarm lymph nodes) after pre-operative chemotherapy and HER2-targeted therapy. Drugs used in chemotherapy, such as paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Trastuzumab and pertuzumab are both a form of "targeted therapy" because they work by attaching themselves to specific molecules (receptors) on the surface of tumor cells, known as HER2 receptors. When these drugs attach to HER2 receptors, the signals that tell the cells to grow are blocked and the tumor cell may be marked for destruction by the body's immune system. Giving paclitaxel, trastuzumab, and pertuzumab may enable fewer chemotherapy drugs to be given without compromising patient outcomes compared to the usual treatment.
Inclusion Criteria:•Patients must have an (ECOG) performance status of 0 or 1•Patient must have histologically confirmed HER2-positive primary invasive breast carcinoma•Patients hormone receptor (estrogen receptor [ER] and progesterone receptor [PR]) status must be known and will be determined by local testing. Patients with either hormone receptor -positive or hormone receptor- negative HER2-positive breast cancer are eligible.•Patients must have clinical stage II and IIIa (T2-3/N0-2/M0) at diagnosis?Patients without nodal involvement (cN0) are eligible if T size greater than equal to 2.0 cm?Patients with nodal involvement (cN1-2) are eligible if T size greater than equal to 1.5 cm•Patient must be willing and able (i.e., have no contraindication) to receive standard adjuvant therapy, consisting of HER2-directed therapy, radiation (if indicated) and endocrine therapy (if ER+) if achieving pCR at surgery•Patient with two separate invasive breast cancers (ipsilateral or bilateral) are eligible if both cancers are HER2-positive and at least one meets protocol eligibility (i.e., greater than equal to 1.5 cm if cN1-2; greater than equal to 2 cm if cN0) (neither tumor can be T4 or N3)•Patients with multifocal or multicentric disease are eligible as long as all tumor foci that were tested for HER2 status at the local institution are HER2-positive, and at least one tumor focus meets eligibility criteria•Patients with a history of other non-breast malignancies are eligible if they have been disease-free for at least 5 years, and are deemed by the investigator to be at low risk for recurrence of that malignancy?Patients with the following cancers are eligible if diagnosed and treated within the past 5 years: cervical cancer in situ, basal cell or squamous cell carcinoma of the skin, and localized papillary or follicular thyroid cancer who have completed recommended treatment including surgery. Patients with any other cancers within the last 5 years are ineligible•Patents must have a left ventricular ejection fraction (LVEF) within normal institutional parameters (or greater than 50%)•Patients must have a bilateral mammogram and diagnostic breast ultrasound (with or without breast magnetic resonance imaging [MRI]) performed at screening (within 42 days of registration)•Baseline imaging of the ipsilateral axilla by ultrasound is mandatory. For subjects with axillary lymph node(s) suspicious on clinical exam or imaging, patient must be willing to have a needle aspiration or core biopsy to determine the presence of metastatic disease in the lymph nodes. A clip must be placed in the involved axillary lymph node•Women of childbearing potential and sexually active males must use accepted and effective method(s) of contraception or to abstain from sexual intercourse for the duration of their participation in the study and for 7 months after the last dose of study treatment•Patient must be willing and able to sign informed consent•Leukocytes greater than equal to 3,000/mcL (obtained equal to less than 28 days prior to protocol registration)•Absolute neutrophil count greater than equal to 1,500/mcL (obtained equal to less than 28 days prior to protocol registration)•Platelets greater than equal to 100,000/mcL (obtained equal to less than 28 days prior to protocol registration)•Total bilirubin equal to less than 1.5 x institutional upper limit of normal (ULN) (obtained equal to less than 28 days prior to protocol registration)•AST(serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) equal to less than 2.5 x institutional ULN (obtained equal to less than 28 days prior to protocol registration)•Creatinine equal to less than 1.5 x institutional ULN (obtained equal to less than 28 days prior to protocol registration)•Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial•For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated•Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral loadExclusion Criteria:•Patient must not have a history of any prior (ipsilateral or contralateral) invasive breast cancer?One exception: a patient with a history of T1N0 triple negative breast cancer diagnosed more than 10 years earlier, who remains disease free is eligible•Patient must not have prior ipsilateral ductal breast carcinoma in situ (DCIS). Patients with prior lobular breast carcinoma in situ (LCIS), atypical hyperplasia, other high risk benign lesions or contralateral DCIS (without evidence of microinvasion) are eligible?NOTE: Patients currently receiving endocrine therapy for prior contralateral DCIS are eligible•Patient must not have stage IV (metastatic) breast cancer?Staging studies (computed tomography [CT] chest/abdomen/pelvis and a bone scan or positron emission tomography [PET]-CT scan) are required for stage III disease or those with abnormal baseline liver function tests (LFTs), symptoms (e.g. new bone pain) or abnormal physical exam findings •Patient must not have T4 and/or N3 disease, including inflammatory breast cancer•Patient must not have any prior treatment for the current breast cancer, including surgery, chemotherapy, hormonal therapy, radiation or experimental therapy•Patients must not have greater than grade 1 peripheral neuropathy of any etiology•Patient must not have a concurrent serious medical condition that would preclude completion of study therapy. For example, uncontrolled hypertension (systolic greater than 180 mm Hg and/or diastolic greater than 100 mm Hg) or clinically significant (i.e. active) cardiovascular disease: cerebrovascular accident/stroke or myocardial infarction within 6 months prior to registration, unstable angina, congestive heart failure (CHF) or serious cardiac arrhythmia requiring medication and other concurrent serious diseases that may interfere with planned treatment•Women must not be pregnant or breast-feeding. Patients must also not expect to conceive from the time of registration, while on study treatment, and until at least 7 months after the last dose of study treatment. All females of childbearing potential must have a blood test or urine study within 14 days prior to registration to rule out pregnancy?A female of childbearing potential is any woman, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: 1) has achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy; or 3) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)
Experimental: Arm A (pCR after surgery) PRE-OPERATIVE/NEOADJUVANT THERAPY: Patients receive either paclitaxel or nab-paclitaxel IV on days 1, 8 and 15, or docetaxel IV on day 1 at the discretion of the treating oncologist. Patients also receive trastuzumab IV on day 1 or days 1, 8, and 15, and pertuzumab IV on day 1. Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity.SURGERY: Within 42 days after last dose of neoadjuvant therapy, patients undergo standard of care lumpectomy and/or mastectomy.POST-OPERATIVE.ADJUVANT THERAPY: Patients with pCR after surgery receive trastuzumab and pertuzumab IV on day 1. Treatment repeats every 21 days for up to 13 cycles in the absence of disease progression or unacceptable toxicity. Patients may also undergo standard of care radiation therapy and receive hormone therapy if appropriate.Experimental: Arm B (residual invasive disease after surgery) PRE-OPERATIVE/NEOADJUVANT THERAPY: Patients receive either paclitaxel or nab-paclitaxel IV on days 1, 8 and 15, or docetaxel IV on day 1 at the discretion of the treating oncologist. Patients also receive trastuzumab IV on day 1 or days 1, 8, and 15, and pertuzumab IV on day 1. Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity.SURGERY: Within 42 days after last dose of neoadjuvant therapy, patients undergo standard of care lumpectomy and/or mastectomy.POST-OPERATIVE/ADJUVANT THERAPY: Patients with remaining tumor after surgery receive standard of care trastuzumab emtansine for 14 doses in the absence of disease progression or unacceptable toxicity. Patients may also receive additional standard of care chemotherapy, as well as hormone therapy if appropriate.