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

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: NCT02774681
Recruitment Status : Terminated (Slow accrual)
First Posted : May 17, 2016
Results First Posted : February 24, 2020
Last Update Posted : April 14, 2020
Sponsor:
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
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)
Hide 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
Arm/Group Title Treatment (Palbociclib)
Hide 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
Hide 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%
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
Hide 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
Hide Outcome Measure Data
Hide 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)
Hide 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
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
Data not collected for analysis
Arm/Group Title Treatment (Palbociclib)
Hide 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)
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
one patient withdrew consent to be followed for survival
Arm/Group Title Treatment (Palbociclib)
Hide 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)
Hide 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
Hide Outcome Measure Data
Hide 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)
Hide 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)
Hide 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
Hide Outcome Measure Data
Hide 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)
Hide 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
Hide 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
Hide Outcome Measure Data
Hide 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)
Hide 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
Hide 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
Hide 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
Hide 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
Hide 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
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)
Hide 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%)    
Hide 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
Hide 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
The study was closed before the accrual goal was met due to slow accrual.
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Massimo Cristofanilli, MD
Organization: Northwestern University
Phone: 312-503-5488
EMail: Massimo.cristofanilli@nm.org
Layout table for additonal information
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