Palbociclib in Treating Patients With Metastatic HER-2 Positive Breast Cancer With Brain Metastasis

• Sponsor: Northwestern University (Other)
• Overall Status: Terminated
• CT.gov ID: NCT02774681
• Collaborator: Pfizer (Industry), National Cancer Institute (NCI) (NIH)
• Enrollment: 12
• Locations: 3
• Arm: 1
• Actual Duration (Months): 41.5
• Patients Per Site: 4
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate if the study drug palbociclib has anti-tumor activity against the breast cancer that has spread to the brain and also to determine the overall radiographic response rate in the CNS. Palbociclib is an anti-cancer medication that has been shown to stop cancer cells from growing. It has been approved in hormone positive breast cancer, along with other hormone therapies and has been found to be effective. The preclinical studies suggest that the drug may also have activity in other types of breast cancer, such as HER2 positive breast cancer. The purpose of this study is to see if the study drug is effective in patients with brain metastasis, who have HER2-positive breast cancer.

Condition or Disease	Intervention/Treatment	Phase
Breast Carcinoma Metastatic in the Brain; Estrogen Receptor Negative; HER2/Neu Negative; HER2/Neu Positive; Progesterone Receptor Negative; Recurrent Breast Carcinoma; Stage IV Breast Cancer	Procedure: Cognitive Assessment; Drug: Palbociclib; Procedure: Quality-of-Life Assessment; Biological: Trastuzumab	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

1. To determine the radiographic response rate in the central nervous system (CNS) in patients with HER2-positive breast cancer who have brain metastasis treated with palbociclib.

SECONDARY OBJECTIVES:

1. To determine the progression-free survival (PFS) and overall survival (OS) in patients with HER2-positive breast cancer who have brain metastasis treated with palbociclib.

2. To determine time to CNS progression in patients with HER2-positive breast cancer who have brain metastasis treated with palbociclib.

3. To determine systemic overall response rate (ORR) in patients with HER2-positive breast cancer who have brain metastasis treated with palbociclib.

4. To determine the safety and tolerability of palbociclib in patients with and HER2-positive breast cancer.

TERTIARY OBJECTIVES:

1. To evaluate circulating tumor deoxyribonucleic acid (DNA) at baseline, 2 month and 4 months; particularly to assess cyclin D1 aberrations, and if this is predictive of responses.

2. To evaluate genomic landscape of available CNS and non-CNS tumors, and describe any discordance.

3. To evaluate cognitive function and quality of life at baseline, 2 and 4 months in patients receiving palbociclib.

OUTLINE:

Patients receive palbociclib orally (PO) daily on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients with HER2 positive breast cancer may also receive trastuzumab intravenously (IV) as standard of care concurrently with palbociclib.

After completion of study treatment, patients are followed up at 3, 6, 9, and 12 months, and then every 6 months for up to 3 years.

Study Design

• Study Type: Interventional
• Actual Enrollment: 12 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Single Arm Study of Palbociclib in Patients With Metastatic HER2-positive Breast Cancer With Brain Metastasis
• Actual Study Start Date: Aug 31, 2016
• Actual Primary Completion Date: Feb 13, 2019
• Actual Study Completion Date: Feb 16, 2020

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Treatment (palbociclib) Patients receive palbociclib PO daily on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients with HER2 positive breast cancer may also receive trastuzumab IV over 30-90 minutes every 3 weeks.

Procedure: Cognitive Assessment; Ancillary studies; Drug: Palbociclib; Given PO; Other Names: Ibrance PD-0332991 PD-332991 ; Procedure: Quality-of-Life Assessment; Ancillary studies; Other Names: Quality of Life Assessment ; Biological: Trastuzumab; Given IV; Other Names: ABP 980 Anti-c-ERB-2 Anti-c-erbB2 Monoclonal Antibody Anti-ERB-2 Anti-erbB-2 Anti-erbB2 Monoclonal Antibody Anti-HER2/c-erbB2 Monoclonal Antibody Anti-p185-HER2 c-erb-2 Monoclonal Antibody HER2 Monoclonal Antibody Herceptin Herceptin Biosimilar PF-05280014 Herceptin Trastuzumab Biosimilar PF-05280014 MoAb HER2 Monoclonal Antibody c-erb-2 Monoclonal Antibody HER2 PF-05280014 rhuMAb HER2 RO0452317 Trastuzumab Biosimilar ABP 980 Trastuzumab Biosimilar PF-05280014

Outcome Measures

Primary Outcome Measures

1. Radiographic Response Rate (RRR) in the CNS in Patients With HER2-positive Breast Cancer Who Have Brain Metastasis Treated With Palbociclib [Up to 3 years]

   Assess the Radiographic Response Rate (RRR) in the CNS by modified Response Assessment in Neuro-Oncology Criteria Brain Metastasis (modifiedRANO-BM). Maximum response prior to disease progression will be used. In General: Complete Response : Disappearance of all lesions Partial Response: At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. Stable Disease: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum of diameters while on study. Progressive Disease: At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression.)

Secondary Outcome Measures

1. Incidence of Adverse Events [Up to 3 years]

   Determine the safety and tolerability of palbociclib in patients with HER2-positive breast cancer by evaluating number, frequency, and severity of adverse events using Common Terminology Criteria for Adverse Events version 4.03. The number of patients that experienced SAEs that were determined to be at least possibly related to study drug are reported below.

2. Overall Survival (OS) [Up to 3 years]

   Evaluate OS in patients with HER2-positive breast cancer who have brain metastasis treated with palbociclib. OS is defined as the time from treatment initiation until death due to any cause. Number of patients remaining alive as of the last follow up date, is reported below.

3. Progression Free Survival (PFS) [Up to 3 years]

   Determine the PFS in patients with HER2-positive breast cancer who have brain metastasis treated with palbociclib where PFS is defined as the time from treatment initiation to documented disease progression or death for any reason. Below shows the number of patient who discontinued treatment due to progression of disease.

4. Overall Response Rate (ORR) [Up to 3 years]

   Evaluate systemic ORR defined as partial response or complete response assessed by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 where: Complete Response = complete disappearance of all lesions Partial Response = At least 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters.

5. Time to CNS Progression [Up to 3 years]

   Time to CNS progression will be defined as the time from treatment initiation to documented disease progression (modified RANO-BM criteria) in the CNS.

Other Outcome Measures

1. Change in Cognitive Function in Patients Receiving Palbociclib [At baseline, 2 months and 4 months]

   Change in cognitive function will be assessed at baseline, 2 months and 4 months and will be collected using patient reported outcome questionnaires: Functional assessment of Cancer Therapy-Cognitive function Version 3.0 (Fact -Cog)

2. Change in Genomic Landscape of Available CNS and Non-CNS Tumors [At baseline]

   To evaluate genomic landscape of available CNS and non-CNS tumors, and describe any discordance. Genotyping of CNS and non-CNS tumors will be performed from archival tissue that will be obtained at baseline. Genotyping will be performed through commercial next generation sequencing assays.

3. Change in Quality of Life in Patients Receiving Palbociclib [At baseline, 2 months and 4 months]

   Quality of life measures will be assessed at baseline, 2 months and 4 and will be collected using patient reported outcome questionnaires: Functional Assessment of Cancer Therapy-Brain (FACT-Br) Version 4.0

4. Cyclin D1 Aberrations Assessed by Circulating Tumor DNA [At baseline, 2 months and 4 months]

   Analyze circulating tumor DNA to assess cyclin D1 aberrations and if this is predictive of response to treatment. Circulating tumor DNA will be collected from whole blood at baseline, 2 and 4 months through commercial next generation sequencing assays.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Histologically confirmed HER2-positive metastatic breast cancer (estrogen and progesterone receptor 0%, HER-2 3+ by immunohistochemistry (IHC); if IHC score of 2, fluorescence in situ hybridization (FISH) ratio must be greater than 2.0; if FISH less than 2.0, HER2 copy number must be greater than 6; NOTE: Brain lesions are not required to have pathologic confirmation

• Patients should not have received > 2 lines of chemotherapy for metastatic disease

• Patients must have a life expectancy of at least 12 weeks at the time of registration

• Eastern Cooperative Oncology Group (ECOG) performance status >= 2

• Measurable disease in the brain, defined as at least 1 lesion measuring >= 5 mm on imaging at the time of registration

• If patients are on corticosteroids, they must have been on a stable or decreasing dose

= 5 days prior to obtaining their baseline gadolinium (Gd)-magnetic resonance imaging (MRI) of brain; this MRI is to be obtained within 28 days of registration; NOTE: If patient needs escalation of steroids prior to therapy, or are on unstable doses of steroids they are not eligible

• Patients who underwent neurosurgery (NSGY) or stereotactic radiosurgery (SRS) to a brain lesion must have a new measureable lesion; NOTE: SRS may be done to a lesion that will not be used for response evaluation and should be done > 2 weeks prior to registration; any NSGY procedure must have been completed > 3 weeks prior to registration

• Patients must not have received systemic therapy within 2 weeks of initiating palbociclib; NOTE: For the HER2-positive cohort, patients on trastuzumab can remain on the drug; no break or washout period required; however, lapatinib, ado-trastuzumab-emtansine, and pertuzumab are prohibited and a minimum wash out period of 2 weeks is required

• Patients must exhibit adequate bone marrow, liver, and renal function, within 14 days prior to registration, defined as:

• Absolute neutrophil count (ANC) >= 1,000/mm^3 (growth factor support is permitted)

• Platelets >= 100,000/mm^3 (may be reached by transfusion)

• Hemoglobin >= 10 gm/dl (may be reached by transfusion)

• Glutamate pyruvate transaminase (GPT)/glutamate oxaloacetate transaminase (GOT) < 3 x upper limit of normal (ULN) (or < 5 x ULN in case of liver metastasis)

• Bilirubin < 3 x ULN (or < 5 x ULN in case of liver metastasis)

• Creatinine < 1.5 x ULN

• Females of child-bearing potential (FOCBP) and males must agree to use adequate contraception prior to study entry, for the duration of study participation, and for 2 weeks following completion of therapy; should a female patient become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately; likewise, if the female partner of a male patient becomes pregnant while participating in this study, he should inform his treating physician immediately; NOTE: A FOCBP is any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:

• Has not undergone a hysterectomy or bilateral oophorectomy

• Has had menses at any time in the preceding 12 consecutive months (and therefore has not been naturally postmenopausal for > 12 months)

• Female patients must have a negative urine pregnancy test within 7 days prior to registration; if urine test is positive, it should be followed by serum pregnancy test

• Patients must sign an informed consent prior to registration and before undergoing any study-specific procedures indicating that they are aware of the investigational nature of this study

• Patient must have the ability to swallow and retain oral medication

• Patient must have the ability to comply with all study requirements

Exclusion Criteria:

• Any uncontrolled neurological symptom attributed to CNS metastasis

• Brain metastasis must not be impending herniation or other significant vasogenic edema requiring increasing steroid doses; lesions must not have frank hemorrhage

• Patients with leptomeningeal disease are not eligible for participation

• Any significant medical illnesses or infection that, in the investigator's opinion, cannot be adequately controlled with appropriate therapy or would compromise the patient's ability to tolerate this therapy are not eligible for participation

• Known human immunodeficiency virus (HIV) positive status

• Known active hepatitis B and/or C

• Previous treatment with palbociclib

• Patients who have a history of allergic reactions attributed to compounds of similar chemical or biologic composition to palbociclib are not eligible; AND/OR patients who have had prior exposure to compounds of similar chemical or biologic composition to palbociclib are not eligible hypersensitivity to any component of palbociclib are not eligible for participation

• Patients being treated with any other experimental agents/clinical trials are not eligible for participation; if the patient is on any investigational agent, a wash-out period of minimum 2 weeks prior to registration is mandatory for the patient to be eligible for the study

• Patients who are on any prohibited medication; a wash-out period of minimum 2 weeks prior to registration is mandatory for the patient to be eligible for the study

• Inability to swallow capsules, malabsorption syndrome or gastrointestinal disease that severely affects the absorption of study drugs, major resection of the stomach or small bowel, or gastric bypass procedure

• Patients who have an uncontrolled intercurrent illness including, but not limited to any of the following, are not eligible:

• Ongoing or active infection requiring systemic treatment

• Symptomatic congestive heart failure

• Unstable angina pectoris

• Cardiac arrhythmia: except atrial fibrillation (AF) and supraventricular tachycardia (SVT) that are controlled by medication

• Psychiatric illness/social situations that would limit compliance with study requirements

• Any other illness or condition that the treating investigator feels would interfere with study compliance or would compromise the patient's safety or study endpoints

• Female patients who are pregnant or nursing are not eligible

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Northwestern University	Chicago	Illinois	United States	60611
2	Northwestern Lake Forest Hospital	Lake Forest	Illinois	United States	60045
3	Houston Methodist Hospital/Houston Methodist Cancer Center	Houston	Texas	United States	77030

Sponsors and Collaborators

• Northwestern University
• Pfizer
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Cristofanilli Massimo, MD, Northwestern University

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Aug 15, 2017

More Information

Publications

None provided.

• Responsible Party: Northwestern University
• ClinicalTrials.gov Identifier: NCT02774681
• Other Study ID Numbers: NU 15B08; STU00202582; NU 15B08; P30CA060553; NCI-2016-00626
• First Posted: May 17, 2016
• Last Update Posted: Apr 14, 2020
• Last Verified: Apr 1, 2020

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Carcinoma; Breast Neoplasms; Brain Neoplasms; Antineoplastic Agents, Immunological; Trastuzumab; Palbociclib; Antibodies; Immunoglobulins; Antibodies, Monoclonal

Study Results

Participant Flow

Recruitment Details	The study opened to accrual May 25, 2016 with the first patient being treated on study August 31,2016. the total accrual goal of 25 patients. The study closed to further accrual January 28, 2019 with 12 patients enrolled on the study

Arm/Group Title	Treatment (Palbociclib)
Arm/Group Description	Patients receive palbociclib PO daily on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients with HER2 positive breast cancer may also receive trastuzumab IV over 30-90 minutes every 3 weeks. Cognitive Assessment: Ancillary studies Palbociclib: Given PO Quality-of-Life Assessment: Ancillary studies Trastuzumab: Given IV
Period Title: Treatment on Study
STARTED	12
Reached 1st Response/2 Cycles	10
Went on to Start Cycle 3	5
COMPLETED	5
NOT COMPLETED	7
Period Title: Treatment on Study
STARTED	12
COMPLETED	0
NOT COMPLETED	12

Baseline Characteristics

Arm/Group Title	Treatment (Palbociclib)
Arm/Group Description	Patients receive palbociclib PO daily on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients with HER2 positive breast cancer may also receive trastuzumab IV over 30-90 minutes every 3 weeks. Cognitive Assessment: Ancillary studies Palbociclib: Given PO Quality-of-Life Assessment: Ancillary studies Trastuzumab: Given IV
Overall Participants	12
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	11 91.7%
>=65 years	1 8.3%
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	55
Sex: Female, Male (Count of Participants)
Female	12 100%
Male	0 0%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	2 16.7%
Not Hispanic or Latino	10 83.3%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	12 100%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (Count of Participants)
United States	12 100%

Outcome Measures

1. Primary Outcome

Title	Radiographic Response Rate (RRR) in the CNS in Patients With HER2-positive Breast Cancer Who Have Brain Metastasis Treated With Palbociclib
Description	Assess the Radiographic Response Rate (RRR) in the CNS by modified Response Assessment in Neuro-Oncology Criteria Brain Metastasis (modifiedRANO-BM). Maximum response prior to disease progression will be used. In General: Complete Response : Disappearance of all lesions Partial Response: At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. Stable Disease: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum of diameters while on study. Progressive Disease: At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression.)
Time Frame	Up to 3 years

Outcome Measure Data

Analysis Population Description

Below table shows best response (Clinical and radiological) of all patients treated on study. Patients that did not complete 2 cycles of treatment required for evaluability for response rate objective are shown. No RRR was not calculated as the study did not met statistical analysis criteria due to study closing before total accrual was met.

Arm/Group Title	Treatment (Palbociclib)
Arm/Group Description	Patients receive palbociclib PO daily on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients with HER2 positive breast cancer may also receive trastuzumab IV over 30-90 minutes every 3 weeks. Cognitive Assessment: Ancillary studies Palbociclib: Given PO Quality-of-Life Assessment: Ancillary studies Trastuzumab: Given IV
Measure Participants	12
Stable Disease CNS	6 50%
Progressive Disease CNS	6 50%

2. Secondary Outcome

Title	Incidence of Adverse Events
Description	Determine the safety and tolerability of palbociclib in patients with HER2-positive breast cancer by evaluating number, frequency, and severity of adverse events using Common Terminology Criteria for Adverse Events version 4.03. The number of patients that experienced SAEs that were determined to be at least possibly related to study drug are reported below.
Time Frame	Up to 3 years

Outcome Measure Data

Analysis Population Description

Data not collected for analysis

Arm/Group Title	Treatment (Palbociclib)
Arm/Group Description	Patients receive palbociclib PO daily on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients with HER2 positive breast cancer may also receive trastuzumab IV over 30-90 minutes every 3 weeks. Cognitive Assessment: Ancillary studies Palbociclib: Given PO Quality-of-Life Assessment: Ancillary studies Trastuzumab: Given IV
Measure Participants	12
Number [participants]	1 8.3%

3. Secondary Outcome

Title	Overall Survival (OS)
Description	Evaluate OS in patients with HER2-positive breast cancer who have brain metastasis treated with palbociclib. OS is defined as the time from treatment initiation until death due to any cause. Number of patients remaining alive as of the last follow up date, is reported below.
Time Frame	Up to 3 years

Outcome Measure Data

Analysis Population Description

one patient withdrew consent to be followed for survival

Arm/Group Title	Treatment (Palbociclib)
Arm/Group Description	Patients receive palbociclib PO daily on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients with HER2 positive breast cancer may also receive trastuzumab IV over 30-90 minutes every 3 weeks. Cognitive Assessment: Ancillary studies Palbociclib: Given PO Quality-of-Life Assessment: Ancillary studies Trastuzumab: Given IV
Measure Participants	11
Number [participants alive]	0 0%

4. Secondary Outcome

Title	Progression Free Survival (PFS)
Description	Determine the PFS in patients with HER2-positive breast cancer who have brain metastasis treated with palbociclib where PFS is defined as the time from treatment initiation to documented disease progression or death for any reason. Below shows the number of patient who discontinued treatment due to progression of disease.
Time Frame	Up to 3 years

Outcome Measure Data

Analysis Population Description

Not sufficient patients enrolled for statistical analysis due to study closing to accrual before the accrual goal was met. Number of patients shown below is the number of patients that discontinued treatment due to progression.

Arm/Group Title	Treatment (Palbociclib)
Arm/Group Description	Patients receive palbociclib PO daily on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients with HER2 positive breast cancer may also receive trastuzumab IV over 30-90 minutes every 3 weeks. Cognitive Assessment: Ancillary studies Palbociclib: Given PO Quality-of-Life Assessment: Ancillary studies Trastuzumab: Given IV
Measure Participants	12
Number [patients]	11

5. Secondary Outcome

Title	Overall Response Rate (ORR)
Description	Evaluate systemic ORR defined as partial response or complete response assessed by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 where: Complete Response = complete disappearance of all lesions Partial Response = At least 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters.
Time Frame	Up to 3 years

Outcome Measure Data

Analysis Population Description

All patient data is shown. Patients that did not complete 2 cycles of treatment required for response are also included as there was no analysis of the data.

Arm/Group Title	Treatment (Palbociclib)
Arm/Group Description	Patients receive palbociclib PO daily on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients with HER2 positive breast cancer may also receive trastuzumab IV over 30-90 minutes every 3 weeks. Cognitive Assessment: Ancillary studies Palbociclib: Given PO Quality-of-Life Assessment: Ancillary studies Trastuzumab: Given IV
Measure Participants	12
Number [participants]	0 0%

6. Secondary Outcome

Title	Time to CNS Progression
Description	Time to CNS progression will be defined as the time from treatment initiation to documented disease progression (modified RANO-BM criteria) in the CNS.
Time Frame	Up to 3 years

Outcome Measure Data

Analysis Population Description

Data not collected. Not sufficient patients enrolled for statistical analysis due to study closing to accrual before the accrual goal was met.

Arm/Group Title	Treatment (Palbociclib)
Arm/Group Description	Patients receive palbociclib PO daily on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients with HER2 positive breast cancer may also receive trastuzumab IV over 30-90 minutes every 3 weeks. Cognitive Assessment: Ancillary studies Palbociclib: Given PO Quality-of-Life Assessment: Ancillary studies Trastuzumab: Given IV
Measure Participants	0

7. Other Pre-specified Outcome

Title	Change in Cognitive Function in Patients Receiving Palbociclib
Description	Change in cognitive function will be assessed at baseline, 2 months and 4 months and will be collected using patient reported outcome questionnaires: Functional assessment of Cancer Therapy-Cognitive function Version 3.0 (Fact -Cog)
Time Frame	At baseline, 2 months and 4 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

8. Other Pre-specified Outcome

Title	Change in Genomic Landscape of Available CNS and Non-CNS Tumors
Description	To evaluate genomic landscape of available CNS and non-CNS tumors, and describe any discordance. Genotyping of CNS and non-CNS tumors will be performed from archival tissue that will be obtained at baseline. Genotyping will be performed through commercial next generation sequencing assays.
Time Frame	At baseline

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

9. Other Pre-specified Outcome

Title	Change in Quality of Life in Patients Receiving Palbociclib
Description	Quality of life measures will be assessed at baseline, 2 months and 4 and will be collected using patient reported outcome questionnaires: Functional Assessment of Cancer Therapy-Brain (FACT-Br) Version 4.0
Time Frame	At baseline, 2 months and 4 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

10. Other Pre-specified Outcome

Title	Cyclin D1 Aberrations Assessed by Circulating Tumor DNA
Description	Analyze circulating tumor DNA to assess cyclin D1 aberrations and if this is predictive of response to treatment. Circulating tumor DNA will be collected from whole blood at baseline, 2 and 4 months through commercial next generation sequencing assays.
Time Frame	At baseline, 2 months and 4 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Time Frame	Adverse Events were collected over a 2 and half year period for the study. For each patient they were collected from treatment initiation until 30 days post the last treatment with range of cycles completed by patients being less than 1 Cycle to 5 Cycles (1 Cycle = 28 Days)
Arm/Group Title	Treatment (Palbociclib)
Arm/Group Description	Patients receive palbociclib PO daily on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients with HER2 positive breast cancer may also receive trastuzumab IV over 30-90 minutes every 3 weeks. Cognitive Assessment: Ancillary studies Palbociclib: Given PO Quality-of-Life Assessment: Ancillary studies Trastuzumab: Given IV
All Cause Mortality
	Treatment (Palbociclib)
	Affected / at Risk (%)	# Events
Total	11/12 (91.7%)
Serious Adverse Events
	Treatment (Palbociclib)
	Affected / at Risk (%)	# Events
Total	6/12 (50%)
Nervous system disorders
Hydrocephalus	1/12 (8.3%)	1
Seizure	2/12 (16.7%)	2
Psychiatric disorders
Confusion	1/12 (8.3%)	1
Vascular disorders
Thromboembolic Event	2/12 (16.7%)	2
Other (Not Including Serious) Adverse Events
	Treatment (Palbociclib)
	Affected / at Risk (%)	# Events
Total	12/12 (100%)
Blood and lymphatic system disorders
Anemia	8/12 (66.7%)
Endocrine disorders
Hypothyroidism	1/12 (8.3%)
Eye disorders
Blurred Vision	1/12 (8.3%)
Watery Eyes	1/12 (8.3%)
Gastrointestinal disorders
Abdominal Pain	1/12 (8.3%)
Diarrhea	2/12 (16.7%)
Nausea	3/12 (25%)
Stomach Pain	1/12 (8.3%)
Vomiting	2/12 (16.7%)
General disorders
Fatigue	5/12 (41.7%)
Flu Like Symptoms	1/12 (8.3%)
Gait Disturbance	2/12 (16.7%)
Malaise	1/12 (8.3%)
Pain	2/12 (16.7%)
Infections and infestations
Tooth Infection	1/12 (8.3%)
Investigations
Alanine aminotransferase increased	2/12 (16.7%)
Alkaline phosphatase increased	1/12 (8.3%)
Aspartate aminotransferase increased	4/12 (33.3%)
Creatinine Increased	2/12 (16.7%)
Lymphocyte Count Decreased	7/12 (58.3%)
Neutrophil Count Decreased	8/12 (66.7%)
Platelet count Decreased	6/12 (50%)
White Blood Cell Decreased	10/12 (83.3%)
Low GFR	1/12 (8.3%)
Metabolism and nutrition disorders
Hyperglycemia	6/12 (50%)
Hypoalbuminemia	3/12 (25%)
Hyponatremia	2/12 (16.7%)
Hypertriglyceridemia	1/12 (8.3%)
Musculoskeletal and connective tissue disorders
Chest Wall Pain	1/12 (8.3%)
Pain in Extremity	1/12 (8.3%)
Nervous system disorders
Cognitive Disturbance	1/12 (8.3%)
Dysphasia	1/12 (8.3%)
Headache	2/12 (16.7%)
Memory Impairment	1/12 (8.3%)
Paresthesia	1/12 (8.3%)
Peripheral Motor Neuropathy	1/12 (8.3%)
Peripheral Sensory Neuropathy	1/12 (8.3%)
Seizure	1/12 (8.3%)
Somnolence	1/12 (8.3%)
Psychiatric disorders
Anxiety	2/12 (16.7%)
Confusion	1/12 (8.3%)
Depression	1/12 (8.3%)
Hallucinations	1/12 (8.3%)
Renal and urinary disorders
Chronic Kidney Disease	1/12 (8.3%)
Reproductive system and breast disorders
Pelvic Pain	1/12 (8.3%)
Respiratory, thoracic and mediastinal disorders
Allergic Rhinitis	1/12 (8.3%)
Dyspnea	1/12 (8.3%)
Hoarseness	1/12 (8.3%)
Laryngeal Inflammation	1/12 (8.3%)
Pleuritic Pain	1/12 (8.3%)
Sore Throat	1/12 (8.3%)
Skin and subcutaneous tissue disorders
Rash Maculo-Papular	1/12 (8.3%)
Stomatitis	1/12 (8.3%)
Vascular disorders
Hypertension	1/12 (8.3%)
Lymphedema	1/12 (8.3%)

Limitations/Caveats

The study was closed before the accrual goal was met due to slow accrual.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.