- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04585724
Stereotactic Radiosurgery With Abemaciclib, Ribociclib, or Palbociclib in Treating Patients With Hormone Receptor Positive Breast Cancer With Brain Metastases
Evaluation of Radiosurgery With Concurrent Cyclin-Dependent Kinase 4/6 Inhibitors in the Treatment of Brain Metastases
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
PRIMARY OBJECTIVE:
I. Prospectively evaluate safety and toxicity of the combination of radiosurgery (SRS) and concurrent CDK 4/6 inhibitors (CDKi) for hormone receptor positive (HR+) breast cancer patients.
SECONDARY OBJECTIVES:
I. Evaluate late toxicity (after 3 months) following SRS and concurrent CDKi. II. Evaluate local control efficacy with combination therapy of SRS and concurrent CDKi.
III. Assess quality of life and neurologic functional outcomes following treatment using standardized questionnaire (Functional Assessment of Cancer Therapy-Brain [FACT-Br]).
IV. Analyze overall survival.
OUTLINE: Patients are assigned to 1 of 3 groups.
GROUP I: Beginning within 2 weeks prior to stereotactic radiosurgery, patients receive abemaciclib orally (PO) twice daily (BID). Treatment continues in the absence of disease progression or unacceptable toxicity.
GROUP II: Beginning within 2 weeks prior to stereotactic radiosurgery, patients receive ribociclib PO once daily (QD) on days 1-21. Treatment continues in the absence of disease progression or unacceptable toxicity.
GROUP III: Beginning within 2 weeks prior to stereotactic radiosurgery, patients receive palbociclib PO QD on days 1-21. Treatment continues in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 30 days, 4-6 weeks post stereotactic radiosurgery, and then every 3 months for up to 1 year.
Study Type
Phase
- Phase 1
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Child
- Adult
- Older Adult
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Pathologic diagnosis of hormone receptor positive (estrogen receptor >= 1 percent or progesterone receptor >= 1 percent) with HER2 negative status, past treatment, or systemic disease status with current clinical diagnosis of up to 10 brain metastases based on contrast-enhanced magnetic resonance imaging (MRI) of the brain
- Plan to start or currently receiving an Food and Drug Administration (FDA)-approved CDK4/6 inhibitor (CDKi), which must be started no later than 2 weeks prior to planned radiosurgery with plan to continue CDKi following radiosurgery
- Up to 10 brain metastases =< 3 centimeters in greatest dimension, measured on radiation planning MRI
- Eastern Cooperative Oncology Group (ECOG)/Zubrod 0-1, or Karnofsky performance status 70-100
- Contrast-enhanced MRI brain within 4 weeks of radiosurgical intervention (radiation planning MRI)
- Patients must be able to sign informed consent prior to study entry, including assent to standard of care post-treatment surveillance contrast-enhanced magnetic resonance imaging of the brain
- Patients who are enrolled in the study, and who continue to be prescribed CDK4/6 inhibitor therapy and develop new brain metastases deemed treatable by radiosurgery, are specifically allowed to be re-treated while on study, and the new treated lesions will be separately counted by treatment category (1 to 3, 4 to 6, or 7 to 10 new treated lesions)
- Patients with prior treated brain metastases (radiosurgery, hypofractionated radiotherapy, or surgery) are eligible for the study regardless of prior history of asymptomatic or symptomatic radiation necrosis and may not be excluded from the study if that is the sole basis for exclusion
Exclusion Criteria:
- Patients with current or prior invasive malignancy unless disease free for minimum of 1 year
- Brain metastases > 3 cm
- Brain lesions causing midline shift or herniation > 1 cm
- Patients with unirradiated post-neurosurgical metastasectomy resection cavities, unless disease-free in the surgical bed for >= 6 months, are prohibited from pilot study enrollment
- No patients who require resection cavity radiation for treatment of a resected brain metastasis (i.e.: standard of care treatment) are eligible for enrollment
- Receipt of chemotherapeutic agents (other than CDK4/6 inhibitors or hormone receptor-related targeted agents) within 2 weeks of planned radiosurgery date
- Prior whole brain or craniospinal radiotherapy
- Fractionated radiation to unrelated central nervous system (CNS) tumor
- Concurrent malignant CNS tumor
- Recurrent or progressive brain metastasis necessitating surgical or medical intervention (i.e.: a non-radiotherapy intervention such as steroids)
- Recurrence or progressive brain metastasis from prior surgical resection necessitating surgical or medical intervention (i.e.: a non-radiotherapy intervention)
- Brain stem metastasis >= 1 cm
- Patients with scleroderma
Severe acute co-morbidity, defined as follows:
- Unstable angina and/or congestive heart failure requiring hospitalization in the last 3 months
- Transmural myocardial infarction within the last 6 months
- Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration
- Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization in the last 6 months or precluding study therapy due to inability to rest supine at the time of registration
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Treatment (abemaciclib)
Beginning within 2 weeks prior to stereotactic radiosurgery, patients receive abemaciclib PO BID.
Treatment continues in the absence of disease progression or unacceptable toxicity.
|
Ancillary studies
Other Names:
Given PO
Other Names:
|
Experimental: Treatment (palbociclib)
Beginning within 2 weeks prior to stereotactic radiosurgery, patients receive palbociclib PO QD on days 1-21.
Treatment continues in the absence of disease progression or unacceptable toxicity.
|
Ancillary studies
Other Names:
Given PO
Other Names:
|
Experimental: Treatment (ribociclib)
Beginning within 2 weeks prior to stereotactic radiosurgery, patients receive ribociclib PO QD on days 1-21.
Treatment continues in the absence of disease progression or unacceptable toxicity.
|
Ancillary studies
Other Names:
Given PO
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Incidence of grade 3+ radiation therapy oncology central nervous system toxicity
Time Frame: At 3 months
|
Rate and frequency of grade 3+ toxicity will be reported.
A 95% exact confidence interval will be estimated using the Clopper-Pearson method.
|
At 3 months
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Symptomatic radiation necrosis (late toxicity)
Time Frame: At 6 and 12 months
|
Will be defined as radiographic (typically on magnetic resonance imaging) changes consistent with radiation induced necrosis and the patient presenting with increased neurological symptoms.
Rate and frequency of late toxicity will be reported, and a 95% exact confidence interval will be estimated.
Symptomatic radiation necrosis similarly will be summarized.
The rate of radiation necrosis will be compared with that of our institutional historical control.
|
At 6 and 12 months
|
Intracranial failure within treated lesion
Time Frame: Up to 1 year
|
Will be defined by progressive lesion either biopsy-proven or with imaging interpretation concordance by both radiation oncologist and neuroradiologist on serial imaging.
The cumulative incidence approach will be used to estimate the failure rates for intracranial failure of treated lesion and distant intracranial failures.
|
Up to 1 year
|
Distant intracranial failure
Time Frame: Up to 1 year
|
New lesions will be defined by new contrast-enhancing brain lesions on magnetic resonance imaging.
The cumulative incidence approach will be used to estimate the failure rates for intracranial failure of treated lesion and distant intracranial failures.
|
Up to 1 year
|
Overall survival
Time Frame: Up to 1 year
|
The Kaplan-Meier method will be used to estimate the overall survival rates.
|
Up to 1 year
|
Quality of life (QoL)
Time Frame: Up to 1 year
|
Will be assessed by Functional Assessment of Cancer Therapy-Brain (FACT-Br) at pre- and post-radiosurgery.
Will be summarized using frequencies and percentages for categorical variables, and mean, standard deviation, median, and range for continuous variables.
Paired tests such as paired t-tests and McNemar's tests will be considered for comparing QoL outcomes pre- versus post-radiosurgery.
|
Up to 1 year
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Jim Zhong, Emory University
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Brain Diseases
- Central Nervous System Diseases
- Nervous System Diseases
- Skin Diseases
- Neoplasms by Site
- Breast Diseases
- Central Nervous System Neoplasms
- Nervous System Neoplasms
- Neoplasms
- Breast Neoplasms
- Brain Neoplasms
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antineoplastic Agents
- Protein Kinase Inhibitors
- Palbociclib
Other Study ID Numbers
- STUDY00000194
- P30CA138292 (U.S. NIH Grant/Contract)
- NCI-2019-02251 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
- RAD4615-19 (Other Identifier: Emory University Hospital/Winship Cancer Institute)
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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