Anastrozole, Palbociclib, Trastuzumab and Pertuzumab in HR-positive, HER2-positive Metastatic Breast

Exclusion Criteria

• •HER2 negative metastatic breast carcinoma defined as 0 or 1+ by IHC or with a FISH ratio (HER2 gene copy/ chromosome 17) \<2 if IHC 2+ by local institution standard protocol
• •Any prior treatment for metastatic breast cancer. (excluding radiation therapy for the purpose of ovarian ablation). Note: Prior adjuvant therapy with trastuzumab and pertuzumab is permitted after a 6 month window following completion of adjuvant therapy has passed.
• •Patients currently receiving anticancer therapies or who have received anticancer therapies within 2 weeks of the start of study drug (including chemotherapy, radiation therapy, and biologics). Patients who have received prior endocrine therapy for fertility purposes will be eligible.
• •Patients, who have had a major surgery or significant traumatic injury within 4 weeks of start of study drug, patients who have not recovered from the side effects of any major surgery (defined as requiring general anesthesia) or patients that may require major surgery during the course of the study
• •Prior treatment with any investigational drug within the preceding 2 weeks
• •Co-administration with strong CYP3A4 inducers (e.g., phenytoin, rifampin, carbamazepine, St John's Wort, bosentan, efavirenz, etravirine, modafinil, and nafcillin), strong CYP3A4 inhibitors (e.g., clarithromycin, indinavir, itraconazole, ketoconazole, lopinavir/ritonavir, nefazodone, nelfinavir, posaconazole, ritonavir, saquinavir, telaprevir, telithromycin, verapamil, and voriconazole), and CYP3A4 substrates (e.g., alfentanil, cyclosporine, dihydroergotamine, ergotamine, everolimus, fentanyl, pimozide, quinidine, sirolimus and tacrolimus). For a current table of Substrates, Inhibitors and Inducers please access the following website:http://www.fda.gov/Drugs/DevelopmentApprovalProcess/" See Appendix C.
• •Uncontrolled brain metastases
• •Leptomeningeal metastases
• •Other malignancies within the past 3 years except for adequately treated carcinoma of the cervix or basal or squamous cell carcinomas of the skin.
• •Patients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study such as:
• •* Symptomatic congestive heart failure of New York heart Association Class III or IV
• •* Unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction within 6 months of start of study drug, serious uncontrolled cardiac arrhythmia or any other clinically significant cardiac disease
• •* Severely impaired lung function as defined as spirometry and DLCO that is 50% of the normal predicted value and/or 02 saturation that is 89% or less at rest on room air
• •* Uncontrolled diabetes as defined by fasting serum glucose \>1.5 x ULN
• •* Active (acute or chronic) or uncontrolled severe infections
• •* Liver disease such as cirrhosis, chronic active hepatitis or chronic persistent hepatitis
• •Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of palbociclib (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or small bowel resection)
• •Patients with an active, bleeding diathesis
• •History of noncompliance to medical regimens
• •Patients unwilling to or unable to comply with the protocol
• •Ongoing alcohol or drug addiction
• •Female patients who are pregnant or breast feeding, or adults of reproductive potential who are not using effective birth control methods. If barrier contraceptives are being used, these must be continued throughout the trial by both sexes. Hormonal contraceptives are not acceptable as a method of contraception. (Women of childbearing potential must have a negative urine or serum pregnancy test within 7 days prior to starting treatment)
• •History of allergic reactions attributed to compounds of similar chemical or biologic composition to palbociclib, anastrozole, trastuzumab or pertuzumab.