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Stereotactic Radiosurgery With Abemaciclib, Ribociclib, or Palbociclib in Treating Patients With Hormone Receptor Positive Breast Cancer With Brain Metastases

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04585724
Recruitment Status : Withdrawn (Closed due to low (0) accrual)
First Posted : October 14, 2020
Last Update Posted : October 18, 2021
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Jim Zhong, Emory University

Brief Summary:
This phase I trial studies the side effects of stereotactic radiosurgery with abemaciclib, ribociclib, or palbociclib in treating patients with hormone receptor positive breast cancer that has spread to the brain (brain metasteses). Stereotactic radiosurgery is a specialized radiation therapy that delivers a single, high dose of radiation directly to the tumor and may cause less damage to normal tissue. Abemaciclib, ribociclib, and palbociclib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving abemaciclib, ribociclib, or palbociclib concurrently with stereotactic radiosurgery may reduce the side effects and/or increase the response to each of the therapies.

Condition or disease Intervention/treatment Phase
Anatomic Stage IV Breast Cancer American Joint Committee on Cancer (AJCC) v8 Metastatic Breast Carcinoma Metastatic Malignant Neoplasm in the Brain Prognostic Stage IV Breast Cancer AJCC v8 Drug: Abemaciclib Drug: Palbociclib Other: Quality-of-Life Assessment Drug: Ribociclib Phase 1

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Evaluation of Radiosurgery With Concurrent Cyclin-Dependent Kinase 4/6 Inhibitors in the Treatment of Brain Metastases
Actual Study Start Date : June 12, 2020
Actual Primary Completion Date : September 13, 2021
Actual Study Completion Date : September 13, 2021

Resource links provided by the National Library of Medicine


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.
Drug: Abemaciclib
Given PO
Other Names:
  • LY-2835219
  • LY2835219
  • Verzenio

Other: Quality-of-Life Assessment
Ancillary studies
Other Name: Quality of Life Assessment

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.
Drug: Palbociclib
Given PO
Other Names:
  • 6-Acetyl-8-cyclopentyl-5-methyl-2-((5-(piperazin-1-yl)pyridin-2-yl)amino)-8h-pyrido(2,3-d)pyrimidin-7-one
  • Ibrance
  • PD 0332991
  • PD 332991
  • PD 991
  • PD-0332991

Other: Quality-of-Life Assessment
Ancillary studies
Other Name: Quality of Life Assessment

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.
Other: Quality-of-Life Assessment
Ancillary studies
Other Name: Quality of Life Assessment

Drug: Ribociclib
Given PO
Other Names:
  • Kisqali
  • LEE-011
  • LEE011




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. Overall survival [ Time Frame: Up to 1 year ]
    The Kaplan-Meier method will be used to estimate the overall survival rates.

  5. 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.



Information from the National Library of Medicine

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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04585724


Sponsors and Collaborators
Emory University
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Jim Zhong Emory University
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Responsible Party: Jim Zhong, Principal Investigator, Emory University
ClinicalTrials.gov Identifier: NCT04585724    
Other Study ID Numbers: STUDY00000194
NCI-2019-02251 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
RAD4615-19 ( Other Identifier: Emory University Hospital/Winship Cancer Institute )
P30CA138292 ( U.S. NIH Grant/Contract )
First Posted: October 14, 2020    Key Record Dates
Last Update Posted: October 18, 2021
Last Verified: October 2021

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Breast Neoplasms
Brain Neoplasms
Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Central Nervous System Neoplasms
Nervous System Neoplasms
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Palbociclib
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action