Palbociclib and Letrozole or Fulvestrant in Treating African American Participants with Hormone Receptor Positive HER2 Negative Advanced Recurrent or Metastatic Breast Cancer

Status: Active


This phase II trial studies how well palbociclib and letrozole or fulvestrant work in treating African American participants with hormone receptor positive HER2 negative breast cancer that has come back or spread to other places in the body. Palbociclib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Estrogen can cause the growth of breast cancer cells. Drugs, such as letrozole and fulvestrant, may lessen the amount of estrogen made by the body. Giving palbociclib and letrozole or fulvestrant may work better in treating African American participants with hormone receptor positive HER2 negative breast cancer.

Eligibility Criteria

Inclusion Criteria

  • Self-identified Black, African or African American women with proven diagnosis of advanced breast cancer (locoregionally recurrent or metastatic disease), either from the primary or a metastatic site
  • Post-menopausal status defined by: a) age ≥ 60 years; b) age < 60 years and cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause; c) documented bilateral oophorectomy; d) medically confirmed ovarian failure OR * Pre/peri-menopausal, ie, not meeting the criteria for being postmenopausal who are also receiving ongoing treatment with gonadotrophin releasing hormone (LHRH) agonists (goserelin or leuprolide); the first injection should occur at least two weeks before study start
  • Estrogen receptor (ER)-positive and/or progesterone receptor (PR)-positive tumor (≥ 1% positive stained cells) based on local laboratory results
  • HER2-negative breast cancer based on local laboratory results (test to be used as per local practice); HER2-negative tumor is determined as immunohistochemistry score 0/1+ or negative by in situ hybridization (fluorescence in situ hybridization [FISH]/chromogenic in situ hybridization [CISH]/silver-enhanced in situ hybridization [SISH]) defined as a HER2/CEP17 ratio < 2 or for single probe assessment a HER2 copy number < 4
  • Patients must be appropriate candidates for letrozole therapy in any line of therapy or for fulvestrant for second line of therapy or beyond
  • Must have received no more than 2 lines of chemotherapy for the treatment of breast cancer, and one for the treatment of advanced breast cancer
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-2
  • Absolute neutrophil count (ANC) ≥ 1,000/mm^3 (1.0 x 10^9/L);
  • Platelets ≥ 100,000/mm^3 (100 x 10^9/L)
  • Hemoglobin ≥ 9 g/dL (90 g/L)
  • Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) ≤ 3 x upper limit of normal (ULN) (≤ 5.0 x ULN if liver metastases present)
  • Alkaline phosphatase ≤ 2.5 x ULN (≤ 5.0 x ULN if bone or liver metastases present)
  • Total serum bilirubin ≤ 1.5 x ULN (≤ 3.0 x ULN if Gilbert’s disease)
  • Serum creatinine ≤ 1.5 x ULN or estimated creatinine clearance ≥ 60 mL/min
  • Resolution of all acute toxic effects of prior therapy, including radiotherapy to grade ≤ 1 (except toxicities not considered a safety risk for the patient) and recovery from surgical procedures
  • Evidence of a personally signed and dated informed consent document indicating that the patient (or a legally acceptable representative) has been informed of all pertinent aspects of the study
  • Patients who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures

Exclusion Criteria

  • Current use of food or drugs known to be potent inhibitors or inducers of CYP3A4
  • Known hypersensitivity to letrozole or fulvestrant, or any of its excipients, or to any palbociclib excipients
  • Active uncontrolled or symptomatic brain metastases; previously treated and clinically stable, as per investigator’s judgment, brain metastases are permitted
  • Previous CDK4/6 inhibitor
  • Other severe acute or chronic medical or psychiatric condition, including recent or active suicidal ideation or behavior, or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study
  • Pregnant or lactating patients; patients of childbearing potential must agree to avoid pregnancy during study treatment and for at least two weeks after the last dose of the study drug

Locations & Contacts

District of Columbia

MedStar Georgetown University Hospital
Status: Active
Contact: Filipa C. Lynce
Phone: 202-444-3677
MedStar Washington Hospital Center
Status: Active
Contact: Christopher Michael Gallagher
Phone: 202-877-0928


University of Chicago Comprehensive Cancer Center
Status: Active
Contact: Olwen Mary Hahn
Phone: 773-702-5381


MedStar Good Samaritan Hospital
Status: Active
Contact: Mahsa Mohebtash
MedStar Union Memorial Hospital
Status: Active
Contact: Mahsa Mohebtash

Trial Objectives and Outline


I. To evaluate the hematological safety of palbociclib with letrozole or fulvestrant in African American women with hormone receptor positive HER2 negative advanced breast cancer.


I. To evaluate delays in palbociclib therapy attributed to neutropenia.

II. To evaluate dose reductions in palbociclib therapy attributed to neutropenia.

III. To evaluate grade 3/4 neutropenia.

IV. To evaluate the efficacy of palbociclib with letrozole or fulvestrant in African American women with hormone receptor (HR) positive HER2 negative advanced breast cancer with evaluable disease.

V. To describe metabolite and exosomal signature and evaluate correlations with disease response.

VI. To describe baseline absolute neutrophil count (ANC) prior to cancer diagnosis and the Duffy Null polymorphism (single nucleotide polymorphism [SNP] rs2814778 at chromosome 1q23.2) and explore correlations with hematological safety.


Participants receive palbociclib orally (PO) once daily (QD) on days 1-21 and letrozole PO QD on days 1-28 or fulvestrant intramuscularly (IM) on days 1 and 15 of course 1 and on day 1 of subsequent courses. Courses repeat every 28 days for up to 12 months in the absence of disease progression or unaccepted toxicity.

After completion of study treatment, participants are followed for 4 weeks.

Trial Phase & Type

Trial Phase

Phase II

Trial Type


Lead Organization

Lead Organization
MedStar Georgetown University Hospital

Principal Investigator
Filipa C. Lynce

Trial IDs

Primary ID 2015-1396
Secondary IDs NCI-2018-00378 ID NCT02692755