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

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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

Tracking Information
First Submitted Date  ICMJE May 13, 2016
First Posted Date  ICMJE May 17, 2016
Results First Submitted Date  ICMJE February 10, 2020
Results First Posted Date  ICMJE February 24, 2020
Last Update Posted Date April 14, 2020
Actual Study Start Date  ICMJE August 31, 2016
Actual Primary Completion Date February 13, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 10, 2020)
Radiographic Response Rate (RRR) in the CNS in Patients With HER2-positive Breast Cancer Who Have Brain Metastasis Treated With Palbociclib [ Time Frame: 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.)
Original Primary Outcome Measures  ICMJE
 (submitted: May 13, 2016)
Radiographic response rate in the CNS in patients with TNBC and HER2- positive breast cancer who have brain metastasis treated with palbociclib [ Time Frame: Up to 3 years ]
Assess the radiographic response rate in the CNS by modified Response Assessment in Neuro-Oncology Criteria Brain Metastasis (modified RANO-BM). Maximum response prior to disease progression will be used.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 20, 2020)
  • Incidence of Adverse Events [ Time Frame: 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.
  • Overall Survival (OS) [ Time Frame: 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.
  • Progression Free Survival (PFS) [ Time Frame: 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.
  • Overall Response Rate (ORR) [ Time Frame: 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.
  • Time to CNS Progression [ Time Frame: 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: May 13, 2016)
  • Incidence of Adverse Events [ Time Frame: Up to 3 years ]
    Determine the safety and tolerability of palbociclib in patients with TNBC and HER2-positive breast cancer by evaluating number, frequency, and severity of adverse events using Common Terminology Criteria for Adverse Events version 4.03
  • Overall Survival (OS) [ Time Frame: Up to 3 years ]
    Evaluate OS in patients with TNBC and 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.
  • Progression Free Survival (PFS) [ Time Frame: Up to 3 years ]
    Determine the PFS in patients with TNBC and 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
  • Overall Response Rate (ORR) [ Time Frame: 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
  • Time to CNS Progression [ Time Frame: 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.
Current Other Pre-specified Outcome Measures
 (submitted: May 13, 2016)
  • Change in Cognitive Function in Patients Receiving Palbociclib [ Time Frame: 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)
  • Change in Genomic Landscape of Available CNS and Non-CNS Tumors [ Time Frame: 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.
  • Change in Quality of Life in Patients Receiving Palbociclib [ Time Frame: 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
  • Cyclin D1 Aberrations Assessed by Circulating Tumor DNA [ Time Frame: 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.
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE Palbociclib in Treating Patients With Metastatic HER-2 Positive Breast Cancer With Brain Metastasis
Official Title  ICMJE A Phase II Single Arm Study of Palbociclib in Patients With Metastatic HER2-positive Breast Cancer With Brain Metastasis
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.
Detailed Description

PRIMARY OBJECTIVES:

I. 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:

I. 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.

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

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

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

TERTIARY OBJECTIVES:

I. 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.

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

III. 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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • 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
Intervention  ICMJE
  • Procedure: Cognitive Assessment
    Ancillary studies
  • Drug: Palbociclib
    Given PO
    Other Names:
    • Ibrance
    • PD-0332991
    • PD-332991
  • Procedure: Quality-of-Life Assessment
    Ancillary studies
    Other Name: 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
Study Arms  ICMJE 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.
Interventions:
  • Procedure: Cognitive Assessment
  • Drug: Palbociclib
  • Procedure: Quality-of-Life Assessment
  • Biological: Trastuzumab
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: February 18, 2019)
12
Original Estimated Enrollment  ICMJE
 (submitted: May 13, 2016)
33
Actual Study Completion Date  ICMJE February 16, 2020
Actual Primary Completion Date February 13, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02774681
Other Study ID Numbers  ICMJE 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) )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Northwestern University
Study Sponsor  ICMJE Northwestern University
Collaborators  ICMJE
  • Pfizer
  • National Cancer Institute (NCI)
Investigators  ICMJE
Principal Investigator: Cristofanilli Massimo, MD Northwestern University
PRS Account Northwestern University
Verification Date April 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP