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

• ClinicalTrials.gov Identifier: NCT02774681
• Recruitment Status: Terminated
• First Posted: May 17, 2016
• Results First Posted: February 24, 2020
• Last Update Posted: April 14, 2020
• Sponsor: Northwestern University
• Collaborators: Pfizer; National Cancer Institute (NCI)
• Information provided by (Responsible Party): Northwestern University

• Study Type: Interventional
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Conditions: 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
• Interventions: Procedure: Cognitive Assessment; Drug: Palbociclib; Procedure: Quality-of-Life Assessment; Biological: Trastuzumab
• Enrollment: 12

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
Pre-assignment Details

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
Reason Not Completed
Progressive Disease	7
Period Title: Follow-Up for 3 Years
Started	12
Completed	0
Not Completed	12
Reason Not Completed
Death	11
Withdrawal by Subject	1

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 Number of Baseline Participants		12
Baseline Analysis Population Description		[Not Specified]
Age, Categorical; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	12 participants
	<=18 years	0 0.0%
	Between 18 and 65 years	11 91.7%
	>=65 years	1 8.3%
Age, Continuous; Median (Full Range); Unit of measure: Years
	Number Analyzed	12 participants
		55; (44 to 77)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	12 participants
	Female	12 100.0%
	Male	0 0.0%
Ethnicity (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	12 participants
	Hispanic or Latino	2 16.7%
	Not Hispanic or Latino	10 83.3%
	Unknown or Not Reported	0 0.0%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	12 participants
	American Indian or Alaska Native	0 0.0%
	Asian	0 0.0%
	Native Hawaiian or Other Pacific Islander	0 0.0%
	Black or African American	0 0.0%
	White	12 100.0%
	More than one race	0 0.0%
	Unknown or Not Reported	0 0.0%
Region of Enrollment; Measure Type: Count of Participants; Unit of measure: Participants
United States	Number Analyzed	12 participants
		12 100.0%

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
Overall Number of Participants Analyzed	12
Measure Type: Count of Participants; Unit of Measure: Participants
Stable Disease CNS	6 50.0%
Progressive Disease CNS	6 50.0%

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
Overall Number of Participants Analyzed	12
Measure Type: Number; Unit of Measure: participants
	1

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
Overall Number of Participants Analyzed	11
Measure Type: Number; Unit of Measure: participants alive
	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
Overall Number of Participants Analyzed	12
Measure Type: Number; Unit of Measure: 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
Overall Number of Participants Analyzed	12
Measure Type: Number; Unit of Measure: participants
	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
Overall Number of Participants Analyzed	0

No data displayed because Outcome Measure has zero total analyzed.

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 Not Reported

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 Not Reported

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 Not Reported

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 Not Reported

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)
Adverse Event Reporting Description	[Not Specified]
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 (%)
Total	11/12 (91.67%)
Serious Adverse Events
	Treatment (Palbociclib)
	Affected / at Risk (%)	# Events
Total	6/12 (50.00%)
Nervous system disorders
Hydrocephalus † 1	1/12 (8.33%)	1
Seizure † 1	2/12 (16.67%)	2
Psychiatric disorders
Confusion † 1	1/12 (8.33%)	1
Vascular disorders
Thromboembolic Event † 1	2/12 (16.67%)	2
1 Term from vocabulary, CTCAE (4.03); † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	Treatment (Palbociclib)
	Affected / at Risk (%)	# Events
Total	12/12 (100.00%)
Blood and lymphatic system disorders
Anemia † 1	8/12 (66.67%)
Endocrine disorders
Hypothyroidism † 1	1/12 (8.33%)
Eye disorders
Blurred Vision † 1	1/12 (8.33%)
Watery Eyes † 1	1/12 (8.33%)
Gastrointestinal disorders
Abdominal Pain † 1	1/12 (8.33%)
Diarrhea † 1	2/12 (16.67%)
Nausea † 1	3/12 (25.00%)
Stomach Pain † 1	1/12 (8.33%)
Vomiting † 1	2/12 (16.67%)
General disorders
Fatigue † 1	5/12 (41.67%)
Flu Like Symptoms † 1	1/12 (8.33%)
Gait Disturbance † 1	2/12 (16.67%)
Malaise † 1	1/12 (8.33%)
Pain † 1	2/12 (16.67%)
Infections and infestations
Tooth Infection † 1	1/12 (8.33%)
Investigations
Alanine aminotransferase increased † 1	2/12 (16.67%)
Alkaline phosphatase increased † 1	1/12 (8.33%)
Aspartate aminotransferase increased † 1	4/12 (33.33%)
Creatinine Increased † 1	2/12 (16.67%)
Lymphocyte Count Decreased † 1	7/12 (58.33%)
Neutrophil Count Decreased † 1	8/12 (66.67%)
Platelet count Decreased † 1	6/12 (50.00%)
White Blood Cell Decreased † 1	10/12 (83.33%)
Low GFR † 1	1/12 (8.33%)
Metabolism and nutrition disorders
Hyperglycemia † 1	6/12 (50.00%)
Hypoalbuminemia † 1	3/12 (25.00%)
Hyponatremia † 1	2/12 (16.67%)
Hypertriglyceridemia † 1	1/12 (8.33%)
Musculoskeletal and connective tissue disorders
Chest Wall Pain † 1	1/12 (8.33%)
Pain in Extremity † 1	1/12 (8.33%)
Nervous system disorders
Cognitive Disturbance † 1	1/12 (8.33%)
Dysphasia † 1	1/12 (8.33%)
Headache † 1	2/12 (16.67%)
Memory Impairment † 1	1/12 (8.33%)
Paresthesia † 1	1/12 (8.33%)
Peripheral Motor Neuropathy † 1	1/12 (8.33%)
Peripheral Sensory Neuropathy † 1	1/12 (8.33%)
Seizure † 1	1/12 (8.33%)
Somnolence † 1	1/12 (8.33%)
Psychiatric disorders
Anxiety † 1	2/12 (16.67%)
Confusion † 1	1/12 (8.33%)
Depression † 1	1/12 (8.33%)
Hallucinations † 1	1/12 (8.33%)
Renal and urinary disorders
Chronic Kidney Disease † 1	1/12 (8.33%)
Reproductive system and breast disorders
Pelvic Pain † 1	1/12 (8.33%)
Respiratory, thoracic and mediastinal disorders
Allergic Rhinitis † 1	1/12 (8.33%)
Dyspnea † 1	1/12 (8.33%)
Hoarseness † 1	1/12 (8.33%)
Laryngeal Inflammation † 1	1/12 (8.33%)
Pleuritic Pain † 1	1/12 (8.33%)
Sore Throat † 1	1/12 (8.33%)
Skin and subcutaneous tissue disorders
Rash Maculo-Papular † 1	1/12 (8.33%)
Stomatitis † 1	1/12 (8.33%)
Vascular disorders
Hypertension † 1	1/12 (8.33%)
Lymphedema † 1	1/12 (8.33%)
1 Term from vocabulary, CTCAE (4.03); † Indicates events were collected by systematic assessment

Limitations and 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.

Results Point of Contact

• Name/Title: Massimo Cristofanilli, MD
• Organization: Northwestern University
• Phone: 312-503-5488
• EMail: Massimo.cristofanilli@nm.org

• Responsible Party: Northwestern University
• ClinicalTrials.gov Identifier: NCT02774681
• Other Study ID Numbers: NU 15B08; STU00202582 ( CTRP (Clinical Trial Reporting Program) ); NU 15B08 ( Other Identifier: Northwestern University ); P30CA060553 ( U.S. NIH Grant/Contract ); NCI-2016-00626 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
• First Submitted: May 13, 2016
• First Posted: May 17, 2016
• Results First Submitted: February 10, 2020
• Results First Posted: February 24, 2020
• Last Update Posted: April 14, 2020