A Phase II Clinical Trial Assessing the Safety of Neoadjuvant Palbociclib in Combination With Endocrine Therapy for Post and Pre-menopausal Patients With Early Stage Hormone Receptor Positive and Her-2/Neu Negative Breast Cancer
Patients with estrogen receptor positive (ER+) and/or progesterone receptor positive (PR+) breast cancer do not achieve good responses with pre-operative chemotherapy. The sensitivity of breast cancer to chemotherapy is often determined by the underlying gene expression pattern and the molecular subtype of the tumor. In addition, not all patients tolerate chemotherapy well. Pre-operative endocrine therapy has emerged as an effective strategy to improve outcomes in patients with early-stage hormone receptor positive breast cancer. This study will assess the role of neo-adjuvant palbociclib (CDK 4/6 inhibitor) in combination with letrozole (aromatase inhibitor) +/-Goserelin (GnRH analogue) to improve overall response and surgical feasibility in post and pre-menopausal hormone receptor positive and Her-2 negative subjects with stage IIA-IIIC breast cancer.
• Histologically confirmed locally advanced stage ER+ and/or PR+ and HER2- breast cancer \[by ASCO/CAP guidelines: primary tumor size 2 cm or greater OR if primary tumor size is \<2 cm with lymph node involvement (Stage II)\] who are candidates for palbociclib in combination with concurrent ovarian suppression and letrozole per treating physician.
• At least 19 years of age.
• ECOG performance status ≤ 2 (see Appendix A)
• Normal bone marrow and organ function as defined below:
‣ Absolute neutrophil count ≥ 1,500/mcl
⁃ Platelets ≥ 100,000/mcl
⁃ Total bilirubin ≤ IULN or total bilirubin ≤ 3.0 x IULN with direct bilirubin within normal range in subjects with documented Gilbert's syndrome
⁃ AST(SGOT)/ALT(SGPT) ≤ 1.5 x IULN (up to 5 x IULN in subjects with liver disease)
⁃ Creatinine ≤ IULN OR creatinine clearance ≥ 60 mL/min/1.73 m2 for subjects with serum creatinine levels above institutional normal
• Pre-menopausal subjects defined by: Age \<60 with no prior bilateral oophorectomy and having menses in the preceding 12 months in the absence of taking chemotherapy, tamoxifen or torimefene or ovarian suppression. If any of these agents were used, measurements of FSH and estradiol have to be made to determine menopausal status.
• Post menopausal subjects defined by: Age \>60 Or absence of menstruation in the preceding 12 months without taking chemotherapy, tamoxifen, torimefene or ovarian suppression. If any of these agents were used, measurements of FSH and estradiol have to be made to determine menopausal status. If none of these are applicable fully, subject may be judged premenopausal according to local policies.
• Participating subjects must agree to use adequate contraception for the duration of protocol treatment and for 6 months after the last treatment with palbociclib. Adequate contraception is defined as one highly effective form (i.e. abstinence, (fe)male sterilization OR two effective forms (e.g. non-hormonal IUD and condom / occlusive cap with spermicidal foam / gel / film / cream / suppository). Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately.
• Able to swallow and retain oral medication.
• Ability to understand and willingness to sign an IRB approved written informed consent document (or that of legally authorized representative, if applicable).