Palbociclib in Combination With Adjuvant Endocrine Therapy for Hormone Receptor Positive, HER2 Negative Invasive Breast Cancer

NCT02040857 | Completed Phase 2 Results DMC

• 1 other identifier: 13-559
• Study Type: interventional
• Target: 162
• Locations: 1 country
• Sites: 10

Brief Summary

This research study is evaluating a drug called Palbociclib in combination with endocrine therapy as a possible treatment for hormone receptor positive breast cancer.

• Palbociclib is a drug that may stop cancer cells from growing. Palbociclib blocks activity of two closely related enzymes (proteins that help chemical reactions in the body occur), called Cyclin D Kinases 4 and 6 (CDK 4/6). These proteins are part of a pathway, or a sequence of steps which is known to regulate cell growth. Laboratory testing has suggested palbociclib may stop the growth of hormone receptor positive breast cancer.
• Endocrine therapy prevents breast cancer cell growth by blocking estrogen stimulation. During this study endocrine therapy will either be tamoxifen or an aromatase inhibitor. It is standard of care for premenopausal women to take tamoxifen and for postmenopausal women to take either an aromatase inhibitor or tamoxifen after a diagnosis of hormone receptor positive breast cancer.

Conditions

Breast Cancer

Keywords

Breast Cancer

Outcome Measures

Primary Outcomes (1)

• 2-Year Treatment Discontinuation Rate

  The 2-year treatment discontinuation rate is the percentage of participants who do not complete the palbociclib treatment per protocol for reasons due to toxicity, withdrawal of consent to be treated, or other events related to tolerability in uncensored participants. Participants who discontinued palbociclib early for reasons that were not treatment-related were censored.

  Evaluate upon completion of palbociclib, up to 2 years of treatment completion.

Secondary Outcomes (4)

• 2-year Treatment Discontinuation Rate by Aromatase Inhibitor and Tamoxifen-based Therapy Subgroup

  Evaluate upon completion of palbociclib, up to 2 years of treatment completion.

• Grade 3-4 Treatment-Related Neutropenia Toxicity Rate

  AE data collected every cycle from the time of the first dose of study treatment, through the study and until 30 days after removal from study or death, whichever occurs first. Therefore, AEs were observed up to 2 years plus 30 days.

• All Grade Treatment-Related Fatigue Toxicity Rate

  AE data collected every cycle from the time of the first dose of study treatment, through the study and until 30 days after removal from study or death, whichever occurs first. Therefore, AEs were observed up to 2 years plus 30 days.

• All GradeTreatment-Related Alopecia Toxicity Rate

  AE data collected every cycle from the time of the first dose of study treatment, through the study and until 30 days after removal from study or death, whichever occurs first. Therefore, AEs were observed up to 2 years plus 30 days.

Study Arms (1)

Palbociclib With Adjuvant Endocrine Therapy

EXPERIMENTAL

* Palbociclib 125 mg PO qd 21 days on, 7 days off * Endocrine Therapy: Tamoxifen 20mg, Letrozole 2.5mg, Anastrozole 1mg, or Exemestane 25mg PO qd

Drug: Palbociclib; Drug: Aromatase Inhibitor

Interventions

Palbociclib DRUG

CDK 4/6 inhibitor

Also known as: PD 0332991-0054, PD-0332991, PD-332991, PF-00080665-73

Palbociclib With Adjuvant Endocrine Therapy

Aromatase Inhibitor DRUG

Endocrine Therapy

Also known as: Femara, Letrozole, Anastrozole, Arimidex, Exemestane, Aromasin, Tamoxifen, Nolvadex

Palbociclib With Adjuvant Endocrine Therapy

Eligibility Criteria

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

You may qualify if:

• Participants must have histologically confirmed hormone receptor positive (HR+) HER2 negative stage II (except T2N0) or stage III invasive breast cancer. Evaluation for metastatic disease is not required in the absence of symptoms.
• Men and both pre- and postmenopausal women are eligible.
• Prior Treatment:
• Participants may have received (neo)adjuvant chemotherapy, but must be at least 30 days after last dose, with no more than grade 1 residual toxicity at time of screening.
• Participants may have received adjuvant radiotherapy, but must be at least 30 days after last dose , with no more than grade 1 residual toxicity at the time of screening.
• If most recent therapy was surgery, participants must be at least 30 days out from definitive surgery with no active wound healing complications.
• Participants must have demonstrated ability to tolerate endocrine therapy by prior successful completion of at least 1 month of tamoxifen or aromatase inhibitor (AI) therapy without significant adverse events, and in the opinion of the treating physician any ongoing toxicity does not preclude ability to continue on tamoxifen or AI for at least a projected 2 year continuous duration. Ongoing use of any endocrine therapy, including tamoxifen, letrozole, anastrozole, or exemestane, is allowed. Patients may enroll within 2 years of beginning endocrine therapy, as long as there is a plan for at least 2 more years of adjuvant endocrine therapy.
• ECOG performance status 0-1
• Age ≥18 years.
• Normal organ and marrow function
• Baseline QTc ≤ 480 ms
• The effects of palbociclib on the developing human fetus are unknown. Women who might become pregnant must use adequate contraception
• Ability to understand and the willingness to sign a written informed consent document

You may not qualify if:

• Concurrent therapy with other investigational agents.
• Prior therapy with any CDK4/6 inhibitor.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to palbociclib.
• Participants receiving any medications or substances that are strong inhibitors or inducers of CYP3A isoenzymes are ineligible.
• Current use of drugs that are known to prolong the QT interval
• Subjects with organ allograft requiring immunosuppression.
• Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Pregnant women are excluded from this study. Breastfeeding should be discontinued prior to entry onto the study.
• Individuals with a history of a different malignancy are ineligible except for the following circumstances. Individuals with a history of other malignancies are eligible if they have been disease-free for at least 5 years and are deemed by the investigator to be at low risk for recurrence of that malignancy. Individuals with the following cancers are eligible if diagnosed and treated within the past 5 years: ductal carcinoma in situ of the breast, cervical cancer in situ, and basal cell or squamous cell carcinoma of the skin.
• No ongoing combination antiretroviral therapy

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead
• Pfizer: collaborator

Study Sites (10)

University of California, San Francisco

San Francisco, California, 94115, United States

Location

Indiana University Health Hospital

Indianapolis, Indiana, 46202, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02214, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

MGH/North Shore Cancer Center

Danvers, Massachusetts, 01923, United States

Location

DF/DWCC at Milford Regional Cancer Center

Milford, Massachusetts, 01757, United States

Location

South Shore Hospital

Weymouth, Massachusetts, 02190, United States

Location

Dana-Farber/New Hampshire Oncology-Hematology

Londonderry, New Hampshire, 03053, United States

Location

University of Pennsylvania-Abramson Cancer Center

Philadelphia, Pennsylvania, 19104, United States

Location

Related Publications (1)

• Mayer EL, DeMichele A, Rugo HS, Miller K, Waks AG, Come SE, Mulvey T, Jeselsohn R, Overmoyer B, Guo H, Barry WT, Huang Bartlett C, Koehler M, Winer EP, Burstein HJ. A phase II feasibility study of palbociclib in combination with adjuvant endocrine therapy for hormone receptor-positive invasive breast carcinoma. Ann Oncol. 2019 Sep 1;30(9):1514-1520. doi: 10.1093/annonc/mdz198.

  PMID: 31250880 RESULT

MeSH Terms

Conditions

Breast Neoplasms

Interventions

palbociclib; Aromatase Inhibitors; Letrozole; Anastrozole; exemestane; Tamoxifen

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Steroid Synthesis Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Estrogen Antagonists; Hormone Antagonists; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Nitriles; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Stilbenes; Benzylidene Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons

Results Point of Contact

• Title: Project Manager
• Organization: Dana-Farber Cancer Institute

ctopm@dfci.harvard.edu

617-632-5313

Study Officials

• Erica Mayer, MD, MPH

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: January 13, 2014
• First Posted: January 20, 2014
• Study Start: January 1, 2014
• Primary Completion: May 1, 2018
• Study Completion: December 27, 2024
• Last Updated: April 29, 2025
• Results First Posted: December 23, 2020

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (10)