Radiation Therapy, Palbociclib, and Hormone Therapy in Treating Breast Cancer Patients With Bone Metastasis

NCT03691493 | Completed Phase 2 Results DMC FDA Drug

• 4 other identifiers: IRB00105944NCI-2018-02000Winship4472-18P30CA138292
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 10

Brief Summary

This phase II trial studies how well radiation therapy given with standard care palbociclib and hormone therapy work in treating patients with breast cancer that has spread from one part of the body to the bone. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Palbociclib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Antihormone therapy, such as fulvestrant, letrozole, anastrozole, exemestane, or tamoxifen, may lessen the amount of estrogen made by the body. Giving radiation therapy, palbociclib, and hormone therapy may work better in treating breast cancer patients with bone metastasis.

Conditions

Anatomic Stage IV Breast Cancer AJCC v8; Estrogen Receptor Positive; HER2/Neu Negative; Metastatic Breast Carcinoma; Metastatic Malignant Neoplasm in the Bone; Progesterone Receptor Positive; Prognostic Stage IV Breast Cancer AJCC v8

Outcome Measures

Primary Outcomes (1)

• Response Rate

  Response rate will be estimated as the number of responders divided by the number of patients evaluated for response. Among patients who present with pain, responders will be considered those patients who have a 2 point decrease in the Brief Pain Inventory (BPI), and among those who do not present with pain (radiotherapy due to risk of unstable fracture or cord compression), responders will be considered those without development of a pathologic fracture or neurologic compromise (cord compression) due to cancer on imaging.

  Up to 3 months post radiation

Secondary Outcomes (10)

• Response Rate Incorporating BPI and Analgesic Measures According to International Bone Consensus Guideline Criteria

  Up to 3 months post radiation

• Number of Participants With Adverse Events Graded According to Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0

  Up to 3 months post radiation

• Progression-free Survival (PFS)

  Up to 44 months post radiation

• Overall Survival (OS)

  Up to 44 months post radiation

• Fatigue as Measured by The Multidimensional Fatigue Inventory (MFI)

  Pre-radiation on day 1, Last Day of radiation (5-10 days), 1 month post radiation, and 3 months post radiation, change last day of radiation, change 1 month post radiation, change 3 months post radiation

Study Arms (1)

Radiation, palbociclib, hormone therapy

EXPERIMENTAL

Patients undergo radiation therapy over 5-10 days and receive palbociclib PO QD on days 1-21. At the discretion of treating physician, patients also receive letrozole, anastrozole, exemestane, or tamoxifen PO QD on days 1-28, or fulvestrant IM on days 1 and 15 of cycle 1 and on day 1 of subsequent cycles. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Drug: Anastrozole; Drug: Exemestane; Drug: Fulvestrant; Drug: Letrozole; Drug: Palbociclib; Radiation: Radiation Therapy; Drug: Tamoxifen

Interventions

Anastrozole DRUG

Given PO

Also known as: Arimidex, ICI D1033, ZD-1033

Radiation, palbociclib, hormone therapy

Exemestane DRUG

Given PO

Also known as: Aromasin, FCE-24304

Radiation, palbociclib, hormone therapy

Fulvestrant DRUG

Given IM

Also known as: Faslodex, ICI 182,780, ZD9238

Radiation, palbociclib, hormone therapy

Letrozole DRUG

Given PO

Also known as: CGS 20267, Femara

Radiation, palbociclib, hormone therapy

Palbociclib DRUG

Given PO

Also known as: Ibrance, PD-0332991

Radiation, palbociclib, hormone therapy

Radiation Therapy RADIATION

Undergo radiation therapy

Also known as: Cancer Radiotherapy, Irradiation, Radiation, Radiotherapeutics

Radiation, palbociclib, hormone therapy

Tamoxifen DRUG

Given PO

Also known as: Soltamox, Nolvadex

Radiation, palbociclib, hormone therapy

Eligibility Criteria

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

You may qualify if:

• Pathologically confirmed metastatic breast cancer
• Known estrogen, progesterone, and human epidermal growth factor receptor 2 (Her2) status of either primary tumor or metastasis
• Metastatic estrogen receptor positive (ER+) or progesterone receptor positive (PR+), Her2/neu negative breast cancer patients with imaging confirming bone metastasis within 60 days of radiation simulation
• Must be actively receiving palbociclib (125 or 100 mg PO daily for 3 weeks followed by a week off during 28-day cycles) plus one of the following hormone therapies for at least 28 days:
• Fulvestrant (500 mg IM injection on days 1 and 15 cycle one and then on day one of each subsequent cycle (28 days) -or-
• Letrozole (2.5 mg PO daily) -or-
• Anastrozole (1 mg PO daily) -or-
• Exemestane (25 mg PO daily) -or-
• Tamoxifen (20 mg PO daily)
• Patients must be willing and able to provide written informed consent/assent for the trial
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
• Karnofsky performance status (KPS) ≥ 60% within 60 days prior to registration
• Must have bone disease that is either symptomatic (i.e. pain) or has a lytic or mixed lytic disease that can be assessed by computed tomography (CT), magnetic resonance imaging (MRI), bone scan or positron emission tomography (PET)/CT within 60 days prior to radiotherapy on this study
• One previous line of chemotherapy in advanced disease is allowed
• Appropriate stage for study entry based on the following diagnostic workup:

You may not qualify if:

• Co-existing or prior invasive non-breast malignancy (except non-melanomatous skin cancer), unless disease free for a minimum of 3 years
• Previous radiation dose, date, fraction size, must be reported for prior invasive malignancy
• Previous palliative radiation to the disease to be treated on protocol (including radiopharmaceuticals)
• Patients prescribed stereotactic body radiation therapy (SBRT) for bone metastasis to be treated on this protocol will be excluded
• Metastases to be treated on protocol located within 2 cm from a previously irradiated structure:
• Spinal cord previously irradiated to \> 40 Gy (delivered in ≤ 3 Gy/fraction)
• Brachial plexus previously irradiated to \> 50 Gy (delivered in ≤ 3 Gy/fraction)
• Small intestine, large intestine, or stomach previously irradiated to \> 45 Gy (delivered in ≤ 3 Gy/fraction)
• Brainstem previously irradiated to \> 50 Gy (delivered in ≤ 3 Gy/fraction)
• Whole lung previously irradiated with prior V20 Gy \> 35% (delivered in ≤ 3 Gy/fraction)
• Untreated brain metastases or unstable/progressive brain metastases (imaging of treated brain metastases must be performed within 28 days of registration for this protocol to confirm brain metastases stability)
• Severe, active co-morbidity such as congestive heart failure (CHF) or unstable angina within last 6 months, transmural myocardial infarction within the last 6 months. Acute bacterial or fungal infection requiring intravenous (IV) antibiotics at time of registration, chronic obstructive pulmonary disease (COPD) or other respiratory illness requiring hospitalization at time of registration
• Lactating females must cease expression of milk prior to registration
• Temperature above 100.4° Fahrenheit
• Previous chemotherapy or radiotherapy within 2 weeks prior to registration or patients who have not recovered from adverse events due to previous chemotherapy and radiotherapy

Sponsors & Collaborators

• Emory University: lead
• Pfizer: collaborator
• National Cancer Institute (NCI): collaborator
• National Institutes of Health (NIH): collaborator

Study Sites (10)

Grady Health System

Atlanta, Georgia, 30303, United States

Location

Emory University Hospital Midtown

Atlanta, Georgia, 30308, United States

Location

Piedmont Hospital

Atlanta, Georgia, 30309, United States

Location

Emory University Hospital/Winship Cancer Institute

Atlanta, Georgia, 30322, United States

Location

Emory Saint Joseph's Hospital

Atlanta, Georgia, 30342, United States

Location

Northside Hospital

Atlanta, Georgia, 30342, United States

Location

Augusta University Medical Center

Augusta, Georgia, 30912, United States

Location

John B. Amos Cancer Center

Columbus, Georgia, 31904, United States

Location

Lewis Cancer and Research Pavilion at Saint Joseph's/Candler

Savannah, Georgia, 31405, United States

Location

Maine Medical Center-Bramhall Campus

Portland, Maine, 04102, United States

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Anastrozole; exemestane; Fulvestrant; Letrozole; palbociclib; Radiotherapy; Radiation; Tamoxifen

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; Estradiol; Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Therapeutics; Physical Phenomena; Stilbenes; Benzylidene Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons

Results Point of Contact

• Title: Dr. Mylin Torres
• Organization: Emory University

matorre@emory.edu

404-778-1900

Study Officials

• Mylin Torres, MD

  Emory University

  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: September 28, 2018
• First Posted: October 1, 2018
• Study Start: February 8, 2019
• Primary Completion: October 13, 2022
• Study Completion: October 13, 2022
• Last Updated: February 17, 2025
• Results First Posted: February 17, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (10)