NCT03628066

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

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 24 (actual)
• Sponsor: NSABP Foundation Inc · Network
• Sex: Female
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed description

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.

Conditions

• Breast Cancer

Interventions

Type	Name	Description
DRUG	Letrozole	Letrozole 2.5 mg by mouth daily for 24 weeks
DRUG	Palbociclib	Palbociclib 125mg by mouth daily for 21 days per 28-day cycle (21 days on, 7 days off) for 24 weeks
DRUG	Goserelin	Goserelin 3.6mg subcutaneous injection x 1 on Day 1 of each 28-day cycle for 24 weeks
DIAGNOSTIC_TEST	Oncotype DX Breast Recurrence Score	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.

Timeline

• Start date: 2018-10-22
• Primary completion: 2020-11-30
• Completion: 2021-01-30
• First posted: 2018-08-14
• Last updated: 2022-04-20

Locations

15 sites across 2 countries: United States, Canada

Regulatory

• FDA-regulated drug study