Clinical Trials /

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

NCT02774681

Description:

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.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Terminated

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Palbociclib in Treating Patients With Metastatic HER-2 Positive Breast Cancer With Brain Metastasis
  • Official Title: A Phase II Single Arm Study of Palbociclib in Patients With Metastatic HER2-positive Breast Cancer With Brain Metastasis

Clinical Trial IDs

  • ORG STUDY ID: NU 15B08
  • SECONDARY ID: STU00202582
  • SECONDARY ID: NU 15B08
  • SECONDARY ID: P30CA060553
  • SECONDARY ID: NCI-2016-00626
  • NCT ID: NCT02774681

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

DrugSynonymsArms
PalbociclibIbrance, PD-0332991, PD-332991Treatment (palbociclib)
TrastuzumabABP 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-05280014Treatment (palbociclib)

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (palbociclib)ExperimentalPatients 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.
  • Palbociclib
  • Trastuzumab

Eligibility Criteria

        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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure: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
Safety Issue:
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.)

Secondary Outcome Measures

Measure:Incidence of Adverse Events
Time Frame:Up to 3 years
Safety Issue:
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.
Measure:Overall Survival (OS)
Time Frame:Up to 3 years
Safety Issue:
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.
Measure:Progression Free Survival (PFS)
Time Frame:Up to 3 years
Safety Issue:
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.
Measure:Overall Response Rate (ORR)
Time Frame:Up to 3 years
Safety Issue:
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.
Measure:Time to CNS Progression
Time Frame:Up to 3 years
Safety Issue:
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.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Terminated
Lead Sponsor:Northwestern University

Last Updated

April 14, 2020