Anatomic Stage IV Breast Cancer American Joint Committee on Cancer (AJCC) v8Phase 1NCT04585724
Stereotactic Radiosurgery With Abemaciclib, Ribociclib, or Palbociclib in Treating Patients With Hormone Receptor Positive Breast Cancer With Brain Metastases
A Phase 1 study testing Abemaciclib, Palbociclib and Quality-of-Life Assessment in people with Anatomic Stage IV Breast Cancer American Joint Committee on Cancer (AJCC) v8 and Metastatic Breast Carcinoma, run by Emory University.
Trial 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). Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Anatomic Stage IV Breast Cancer American Joint Committee on Cancer (AJCC) v8, Metastatic Breast Carcinoma, Metastatic Malignant Neoplasm in the Brain
- What is being tested?
- Abemaciclib, Palbociclib and Quality-of-Life Assessment
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- 12 Jun 2020to 13 Sep 2021
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
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- 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
About this study
Official title: Evaluation of Radiosurgery With Concurrent Cyclin-Dependent Kinase 4/6 Inhibitors in the Treatment of Brain Metastases
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.
Read the detailed description
PRIMARY OBJECTIVE:
- 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:
- 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.
- Conditions
- 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
- Being tested
- Abemaciclib, Palbociclib, Quality-of-Life Assessment, Ribociclib
- Medical subject headings
- Breast Neoplasms, Brain Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AbemaciclibDrug
Also called LY-2835219, LY2835219, Verzenio
Given PO
PalbociclibDrug
Also called 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
Given PO
Quality-of-Life AssessmentOther
Also called Quality of Life Assessment
Ancillary studies
RibociclibDrug
Also called Kisqali, LEE-011, LEE011
Given PO
| Study group | Role | What they receive |
|---|---|---|
| Treatment (abemaciclib) | Experimental | Beginning within 2 weeks prior to stereotactic radiosurgery, patients receive abemaciclib PO BID. Treatment continues in the absence of disease progression or unacceptable toxicity. Receives: Drug: Abemaciclib; Other: Quality-of-Life Assessment |
| Treatment (palbociclib) | Experimental | 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. Receives: Drug: Palbociclib; Other: Quality-of-Life Assessment |
| Treatment (ribociclib) | Experimental | 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. Receives: Other: Quality-of-Life Assessment; Drug: Ribociclib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of grade 3+ radiation therapy oncology central nervous system toxicity
Rate and frequency of grade 3+ toxicity will be reported. A 95% exact confidence interval will be estimated using the Clopper-Pearson method.
Measured: At 3 months
Secondary outcomes (5)
Symptomatic radiation necrosis (late toxicity)
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.
Measured: At 6 and 12 months
Intracranial failure within treated lesion
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.
Measured: Up to 1 year
Distant intracranial failure
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.
Measured: Up to 1 year
Overall survival
The Kaplan-Meier method will be used to estimate the overall survival rates.
Measured: Up to 1 year
Quality of life (QoL)
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.
Measured: Up to 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Oct 2020
- Study start12 Jun 2020
- Primary completion13 Sep 2021
- Study completion13 Sep 2021
Why it stopped: Closed due to low (0) accrual
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Anatomic Stage IV Breast Cancer American Joint Committee on Cancer (AJCC) v8Studies of the same condition, open and under way.
- More trials run by Emory UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Emory University
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Principal investigator, Jim Zhong, Emory University
- Investigators
- Jim Zhong, Principal investigator, Emory University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04585724
- Sponsor's protocol ID
- STUDY00000194
- Other IDs
- NCI-2019-02251, RAD4615-19, P30CA138292
- Status last verified
- Oct 2021
- First submitted
- 7 Oct 2020
- Last updated
- 18 Oct 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Oct 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of Radiosurgery With Concurrent Cyclin-Dependent Kinase 4/6 Inhibitors in the Treatment of Brain Metastases
- ClinicalTrials.gov ID
- NCT04585724
- Acronym / sponsor ID
- STUDY00000194
- Conditions
- 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
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Closed due to low (0) accrual
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Emory UniversityUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- 12 Jun 2020 (actual)
- Primary completion
- 13 Sep 2021 (actual)
- Study completion
- 13 Sep 2021 (actual)
- First posted
- 14 Oct 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
PRIMARY OBJECTIVE:
- 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:
- 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 design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Treatment (abemaciclib) | Experimental | Drug: Abemaciclib, Other: Quality-of-Life AssessmentBeginning within 2 weeks prior to stereotactic radiosurgery, patients receive abemaciclib PO BID. Treatment continues in the absence of disease progression or unacceptable toxicity. |
| Treatment (palbociclib) | Experimental | Drug: Palbociclib, Other: Quality-of-Life AssessmentBeginning 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. |
| Treatment (ribociclib) | Experimental | Other: Quality-of-Life Assessment, Drug: RibociclibBeginning 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. |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (8 listed)
- 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)
Key exclusion criteria (18 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AbemaciclibAlso: LY-2835219, LY2835219, VerzenioGiven PO | Drug | Treatment (abemaciclib) |
| PalbociclibAlso: 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 332991Given PO | Drug | Treatment (palbociclib) |
| Quality-of-Life AssessmentAlso: Quality of Life AssessmentAncillary studies | Other | Treatment (abemaciclib), Treatment (palbociclib), Treatment (ribociclib) |
| RibociclibAlso: Kisqali, LEE-011, LEE011Given PO | Drug | Treatment (ribociclib) |
Primary outcome
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.
5 secondary outcomes
Symptomatic radiation necrosis (late toxicity)
Time frame: At 6 and 12 months
Intracranial failure within treated lesion
Time frame: Up to 1 year
Distant intracranial failure
Time frame: Up to 1 year
Overall survival
Time frame: Up to 1 year
Quality of life (QoL)
Time frame: Up to 1 year
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Oct 2021.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jim Zhong principal investigator
Emory University
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Abemaciclib, Palbociclib and Quality-of-Life Assessment in people with Anatomic Stage IV Breast Cancer American Joint Committee on Cancer (AJCC) v8 and Metastatic Breast Carcinoma, run by Emory University.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 18 Oct 2021. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of grade 3+ radiation therapy oncology central nervous system toxicity (time frame: At 3 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Oct 2021.