Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Symptoms and General Pathology

Breast Neoplasms

Recurrence

Breast Diseases

Skin Diseases

Antineoplastic Agents

All Drugs and Chemicals

Letrozole

Estrogens

Palbociclib

Goserelin

Aromatase Inhibitors

Enzyme Inhibitors

Estrogen Antagonists

Estrogen Receptor Antagonists

Hormones

Hormone Antagonists

Protein Kinase Inhibitors

Antineoplastic Agents, Hormonal

Oncotype DX Breast recurrence score on diagnostic tissue

Daily Letrozole for 24 weeks + Palbociclib daily for 24 weeks + Goserelin weekly for 24 weeks

Letrozole 2.5 mg by mouth daily for 24 weeks

Palbociclib 125mg by mouth daily for 21 days per 28-day cycle (21 days on, 7 days off) for 24 weeks

Goserelin 3.6mg subcutaneous injection x 1 on Day 1 of each 28-day cycle for 24 weeks

Prior to assignment to Arm 1 the Oncotype DX diagnostic test will be conducted on diagnostic tissue to assign a recurrence score for stratification to cohort 1 or 2.

Oncotype DX Breast Recurrence Score

Norman Wolmark, MD

This study will look at the safety and effectiveness of the combination of palbociclib and letrozole and ovarian suppression for premenopausal patients who have ER-positive/HER2-negative breast cancer that has not yet been treated.

NSABP FB-13 is a phase II, open label study to examine the biological and clinical effect of neoadjuvant endocrine therapy with letrozole, palbociclib and ovarian suppression in premenopausal patients with estrogen-receptor (ER) positive, HER2-negative, early invasive breast cancer.

Premenopausal women newly diagnosed with ER-positive/HER2-negative early breast cancer who are suitable candidates for neoadjuvant endocrine therapy will be invited to join the FB-13 trial. A screening Oncotype DX Breast Recurrence Score® will be performed by Genomic Health, Inc. (GHI) on the diagnostic tissue of consenting patients to verify eligibility.

Patients will be stratified into one of two approximately equal sized cohorts based on baseline Breast Recurrence Score (RS) (cohort 1: patients with RS less than 11 or cohort 2: patients with RS 11 to less than 26).

Patients in both cohorts will receive letrozole 2.5 mg by mouth daily, palbociclib 125 mg by mouth daily for 21 days of a 28 day cycle, and goserelin 3.6 mg subcutaneous injection on Day 1 of each 28 day cycle. At Week 6 of study therapy, patients will have two core-cut biopsies. Patients from both cohorts who have a Ki67 less than 10% level will continue receiving study therapy for a total of 6 cycles. Patients with a persistent Ki67 greater than or equal to 10% at week 6 will permanently discontinue study therapy and begin neoadjuvant chemotherapy or proceed to surgery at the discretion of the treating physician.

Pre-treatment samples and post-surgical samples will be collected and analysed to identify subgroups of patients who may derive the most clinical benefit. The results of the biological analyses may allow a target sensitive population to be selected for future trials. The tissue collected in FB-13 will form an integral part of the primary analyses; so all core biopsies in this trial will be mandated for patients.

Two core-cut biopsies will be collected from each patient at baseline, after 6 weeks of study therapy, and upon completion of study therapy (24 weeks) at the time of definitive surgery.

Blood samples will be collected at baseline, 4 weeks, and at 24 weeks for estrone and estradiol levels to demonstrate ovarian suppression. A 4-week estradiol level in the postmenopausal range will be required to receive further treatment on study.

Biological and Clinical Effects of Palbociclib With Ovarian Suppression and Letrozole in the Neoadjuvant Treatment of Breast Cancer

An Assessment of the Biological and Clinical Effects of Palbociclib (PD 0332991) With Ovarian Suppression and Letrozole in the Neoadjuvant Treatment of Patients With Premenopausal Estrogen-Receptor Positive/HER2-Negative Primary Breast Cancer

Percentage of patients with a Ki67 less than 2.7%

Objective response rate determined by breast tumor assessment measured by clinical exam and ultrasound

Percentage of patients with absence of invasive cancer in surgical specimens

Correlation of the Oncotype DX Breast Recurrence Score® with clinical Complete Response

Correlation of the Oncotype DX Breast Recurrence Score® with pathologic Complete Response

Correlation of the Oncotype DX Breast Recurrence Score® with Complete Cell cycle arrest rate

Changes between surgical intent declared at study start and actual surgery received after treatment

Spots Global Cancer Trial Database for oncotype dx breast recurrence score