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

NCT03628066 | Completed Phase 2 FDA Drug

• 1 other identifier: NSABP FB-13
• Study Type: interventional
• Target: 24
• Locations: 2 countries
• Sites: 15

Brief 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.

Conditions

Breast Cancer

Keywords

Ovarian Suppression; Neoadjuvant; Premenopausal; Estrogen-Receptor Positive; HER2-Negative; Primary; Palbociclib; Letrozole; Goserelin; Ki67; Oncotype DX Breast Recurrence Score; Open-Label

Outcome Measures

Primary Outcomes (1)

• Complete Cell cycle arrest

  Percentage of patients with a Ki67 less than 2.7%

  From study entry to the time of the 6 week tumor biopsy to assess Ki67, approximately 6 weeks

Secondary Outcomes (9)

• Objective response rate

  From study entry to the 24 week clinical assessment/ultrasound, approximately 24 weeks

• Pathologic complete response to study therapy (breast)

  From study entry to time of surgery, generally 3 to 4 weeks after completion of study therapy at approximately 28 weeks

• Pathologic complete response to study therapy (breast with nodes)

  From study entry to time of surgery, generally 3 to 4 weeks after completion of study therapy at approximately 28 weeks

• Correlation between Oncotype DX Breast Recurrence Score® and clinical Complete Response (cCR)

  From study entry to the 24 week clinical assessment/ultrasound, approximately 24 weeks

• Correlation between Oncotype DX Breast Recurrence Score® and pathologic Complete Response (pCR)

  From study entry to time of surgery, generally 3 to 4 weeks after completion of study therapy at approximately 28 weeks

Study Arms (1)

Arm 1

EXPERIMENTAL

Oncotype DX Breast recurrence score on diagnostic tissue Daily Letrozole for 24 weeks + Palbociclib daily for 24 weeks + Goserelin weekly for 24 weeks

Drug: Letrozole; Drug: Palbociclib; Drug: Goserelin; Diagnostic Test: Oncotype DX Breast Recurrence Score

Interventions

Letrozole DRUG

Letrozole 2.5 mg by mouth daily for 24 weeks

Also known as: Femara

Arm 1

Palbociclib DRUG

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

Also known as: Ibrance

Arm 1

Goserelin DRUG

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

Also known as: Zoladex

Arm 1

Oncotype DX Breast Recurrence Score DIAGNOSTIC_TEST

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.

Arm 1

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must be premenopausal. Patients with a hysterectomy: menopausal status must be confirmed by estradiol and FSH.
• Operable hormonal receptor (HR) positive (ER/PR greater than or equal to 10%), HER2- negative, invasive early breast cancer, suitable for neoadjuvant AI treatment and ovarian suppression; HR- positive and HER2-negative as determined by American Society of Clinical Oncology/College of American Pathologists (ASCO-CAP ) guidelines.
• Diagnostic breast tissue must have an Oncotype DX Breast Recurrence Score® of less than 26 as determined by Genomic Health, Inc.
• No known severe hypersensitivity reactions to compounds similar to palbociclib or palbociclib excipients or to endocrine treatments.
• A breast tumor with an ultrasound size of at least 2.0 cm.
• Patients must have the ability to swallow oral medication.
• ECOG performance status of 0 or 1.
• At the time of randomization, blood counts performed within 2 weeks prior to randomization must meet the following criteria:
• ANC must be greater than or equal to 1500/mm3
• Platelet count must be greater than or equal to 100,000/mm3
• Hemoglobin must be greater than or equal to 10g/dL.
• INR must be within normal limits of the local laboratory ranges. For laboratories that do not report an ULN for the INR assay, use less than or equal to 1.2 as the value for the ULN.
• The following criteria for evidence of adequate hepatic function performed within 2 weeks prior to study entry must be met:
• Total bilirubin must be less than or equal to ULN for the lab unless the patient has a bilirubin elevation greater than ULN to 1.5 x ULN due to Gilbert's disease or similar syndrome involving slow conjugation of bilirubin; and
• Alkaline phosphatase must be must be less than or equal to 1.5 x ULN for the lab; and

You may not qualify if:

• Active hepatitis B or hepatitis C with abnormal liver function tests.
• HIV positive patients receiving antivirals.
• Inflammatory/inoperable breast cancer.
• HER2-positive as determined using ASCO-CAP Guidelines.
• Oncotype Dx Breast Recurrence Score® result on diagnostic breast tissue greater than or equal to 26.
• Prior endocrine therapy for breast cancer.
• Any invasive malignancy within previous 5 years (other than basal cell carcinoma or cervical carcinoma in situ).
• Other nonmalignant systemic disease that would preclude the patient from receiving study treatment or would prevent required follow up such as:
• Active infection or chronic infection requiring chronic suppressive antibiotics;
• Malabsorption syndrome, ulcerative colitis, inflammatory bowel disease, resection of the stomach or small bowel, or other disease or condition significantly affecting gastrointestinal function;
• Chronic daily treatment with corticosteroids with a dose of greater than or equal to 10 mg/day methylprednisolone equivalent (excluding inhaled steroids);
• Seizure disorders requiring medication.
• Diagnosis by fine needle aspiration (FNA) alone or excisional biopsy or lumpectomy performed prior to study entry.
• Surgical axillary staging procedure prior to study procedure (with exception of FNA or core biopsy).
• Definitive clinical or radiologic evidence of metastatic disease.

Sponsors & Collaborators

• NSABP Foundation Inc: lead
• Genomic Health®, Inc.: collaborator
• Pfizer: collaborator

Study Sites (15)

Breast Cancer Care Specialist

Fountain Valley, California, 92708, United States

Location

Orange Coast Blood and Cancer Care

Fountain Valley, California, 92708, United States

Location

Saddleback Memorial Medical Center

Laguna Hills, California, 92653, United States

Location

Coast Hematology-Oncology Associates Medical Group

Long Beach, California, 90806, United States

Location

Long Beach Memorial Medical Center

Long Beach, California, 90806, United States

Location

Oncology Hematology Consultants

Long Beach, California, 90806, United States

Location

Cancer Care Specialists of Central Illinois

Decatur, Illinois, 62526, United States

Location

Avera Cancer Institute-Sioux Falls

Sioux Falls, South Dakota, 57105, United States

Location

Lester and Sue Smith Breast Center

Houston, Texas, 77030, United States

Location

West Virginia University

Morgantown, West Virginia, 26506, United States

Location

Froedtert Hospital

Milwaukee, Wisconsin, 53226, United States

Location

Centre Hospitalier de l'Universite de Montreal

Montreal, Quebec, H2X-3E4, Canada

Location

Jewish General Hospital - Montreal

Montreal, Quebec, H3T 1E2, Canada

Location

McGill University Health Centre-Cedars Cancer Centre

Montreal, Quebec, H4A 3J1, Canada

Location

CHU de Quebec - Hopital de Saint-Sacrement

Québec, Quebec, G1S 4L8, Canada

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Letrozole; palbociclib; Goserelin

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Nitriles; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Gonadotropin-Releasing Hormone; Pituitary Hormone-Releasing Hormones; Hypothalamic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins

Study Officials

• Norman Wolmark, MD

  NSABP Foundation Inc

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 27, 2018
• First Posted: August 14, 2018
• Study Start: October 22, 2018
• Primary Completion: November 30, 2020
• Study Completion: January 30, 2021
• Last Updated: April 20, 2022

Record last verified: 2022-04

Locations

US (11); CA (4)