Radiation Therapy, Palbociclib, and Hormone Therapy in Treating Breast Cancer Patients with Bone Metastasis
18 Years and older, Male and Female
Winship4472-18 (primary)
NCI-2018-02000
IRB00105944
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 (bone metastasis). 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. Estrogen can cause the growth of breast cancer cells. Letrozole, anastrozole, and exemestane lowers the amount of estrogen made by the body. This may help stop the growth of tumor cells that need estrogen to grow. Fulvestrant and tamoxifen blocks the use of estrogen by the tumor cells. Giving radiation therapy, palbociclib, and hormone therapy may work better in treating breast cancer patients with bone metastasis.
Objectives
PRIMARY OBJECTIVE:
I. To evaluate the response rate three months post conventionally fractionated radiotherapy, relative to baseline, for bone metastases in breast cancer patients receiving concurrent palbociclib and hormone therapy treatment.
SECONDARY OBJECTIVES:
I. To determine whether conventionally fractionated radiotherapy in combination with palbociclib and hormone therapy in breast cancer patients with bone metastases adversely increases the frequency and severity of palbociclib toxicities including grade 3 neutropenia.
II. To determine whether radiotherapy in combination with palbociclib in breast cancer patients with bone metastases adversely increases the frequency and severity of radiotherapy toxicities including neurological and bone injury.
III. To assess fatigue, quality of life, and depression before and after radiotherapy for bone metastases in metastatic breast cancer patients treated with palbociclib.
IV. To determine progression free survival (PFS) and overall survival (OS) in breast cancer patients treated with palbociclib and concurrent radiotherapy to bone metastases.
V. To evaluate the relationship between volume of irradiated bone and side effects of treatment, including leukopenia and neutropenia.
TRANSLATIONAL RESEARCH OBJECTIVES:
I. To collect, store, and analyze circulating tumor-derived deoxyribonucleic acid (ctDNA) in metastatic breast cancer patients treated with palbociclib and radiotherapy to bone metastases and to determine the relationship between ctDNA and responders versus non-responders, PFS, and OS.
II. To collect, store, and analyze plasma for inflammatory cytokine measurements and determine their relationship with fatigue, depression, and quality of life before and after radiotherapy for bone metastases in metastatic breast cancer patients treated with palbociclib.
III. To collect, store, and analyze ribonucleic acid (RNA) for gene expression to identify functional biology processes over-represented in genes differentially regulated among patients who develop toxicities versus those who do not and those who are responders versus those who are not and to identify transcriptional regulatory pathways driving observed differences in gene expression.
OUTLINE:
Patients undergo radiation therapy over 5-10 days and receive palbociclib orally (PO) once daily (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 intramuscularly (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.
After completion of study treatment, patients are followed up at 1 and 3 months.
Eligibility
- Pathologically confirmed metastatic breast cancer
- Known estrogen, progesterone, and 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 or 75 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 (500mg 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 (1mg PO daily) -or-
* Exemestane (25mg PO daily) -or-
* Tamoxifen (20mg PO daily)
- Patients must be willing and able to provide written informed consent/assent for the trial
- Age >= 18 years
- 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:
* History and physical examination within 60 days prior to registration
* Clinical grade CT scans of the chest, abdomen, and pelvis with radionuclide bone scan OR whole body PET/CT documenting metastatic disease prior to radiotherapy on this protocol or MRI documenting site of metastatic disease to be treated on protocol
- Patient must be eligible for palliative radiotherapy (conventional radiation either 30 Gy in 10 fractions or 20 Gy in 5 fractions) for up to 4 separate anatomic regions containing bone metastases defined by 4 separate and not overlapping radiation plans
- Absolute neutrophil count >= 1000/mcl (obtained within 14 days prior to registration on study)
- Platelets >= 75,000 mm^3 (obtained within 14 days prior to registration on study)
- Hemoglobin >= 8.0 g/dl (obtained within 14 days prior to registration on study) (Note: The use of transfusion or other intervention to achieve hemoglobin [Hgb] >= 8.0g/dl is acceptable) (obtained within 14 days prior to registration on study)
- For females of child-bearing potential, negative serum or urine pregnancy test within 14 days prior to radiation simulation
- The patient or a legally authorized representative must provide study-specific informed consent prior to study entry
- Prior Treatment:
* Patients may or may not have received radiotherapy or neoadjuvant or adjuvant chemotherapy in the treatment of their initial, non-metastatic breast cancer, but must be entered on study after their last dose of radiotherapy, last cycle of chemotherapy and biologic therapy (if applicable) and have sufficient resolution of side effects per physician assessment at time of radiotherapy
* Patients must have no active wound healing issues from surgery and sufficient resolution of surgical side effects, per physician assessment, at time of radiotherapy
* If patients have one line of chemotherapy for advanced disease, patients must be entered on study after their last dose of chemotherapy and have sufficient resolution of side effects per physician assessment at time of radiotherapy
* Patients must have already initiated palbociclib (3 weeks on, 1 week off) and hormone therapy for at least 28 days prior to radiotherapy
* During radiotherapy, no other investigation or commercial agents or therapy for cancer other than palbociclib, bisphosphonates, rank ligand inhibitors, and hormone therapy should be administered
* Patients may have received bisphosphonates or rank ligand inhibitors prior to enrollment on study
Treatment Sites in Georgia
1100 Johnson Ferry Road
Suite 600
Sandy Springs, GA 30342
404-256-4777 ext 9242
www.gacancer.com
960 Johnson Ferry Road
Suite 130
Atlanta, GA 30342
404-303-3355
www.ugynonc.com
**Clinical trials are research studies that involve people. These studies test new ways to prevent, detect, diagnose, or treat diseases. People who take part in cancer clinical trials have an opportunity to contribute to scientists’ knowledge about cancer and to help in the development of improved cancer treatments. They also receive state-of-the-art care from cancer experts...
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