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PALINA: Palbociclib / Letrozole or Fulvestrant in African American Women With HR+ HER2- Breast Cancer

Sponsor
Georgetown University (Other)
Overall Status
Completed
CT.gov ID
NCT02692755
Collaborator
University of Chicago (Other), Thomas Jefferson University (Other)
35
Enrollment
6
Locations
1
Arm
54.7
Actual Duration (Months)
5.8
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study aims to evaluate the hematological safety of palbociclib with letrozole and fulvestrant in African American women with hormone receptor positive HER2 negative advanced breast cancer. Hematological safety is a composite endpoint of episodes of febrile neutropenia and treatment discontinuation due to neutropenia according to current recommendations for management of neutropenia

Condition or Disease Intervention/Treatment Phase
  • Drug: Palbociclib + Letrozole or Fulvestrant
 Phase 2/Phase 3

Detailed Description

The study is designed to assess the rate of completion of planned oncology therapy in the absence of a hematological event defined as episodes of febrile neutropenia and treatment discontinuation due to neutropenia. A completion rate of 80% is considered of clinical relevance as to benefit breast cancer patients who are at a higher risk of having ethnic neutropenia where as a completion rate of 60% is considered poor and to justify additional safety studies. A two stage design with a total of 35 patients is used to test if the completion rate is at least 80% versus if it is below 60% with 80% power at a significance level of 5%.

An exact confidence interval of the completion rate will be calculated. Investigators estimate there will be no more than a 10% rate of febrile neutropenia. Due to the small sample size, the analysis of secondary endpoints will be descriptive and will not include specific hypothesis testing.

Study Design

Study Type:
Interventional
Actual Enrollment :
35 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Phase II Safety Study of Palbociclib in Combination With Letrozole or Fulvestrant in African American Women With Hormone Receptor Positive HER2 Negative Advanced Breast Cancer
Actual Study Start Date :
Sep 1, 2016
Actual Primary Completion Date :
Dec 16, 2019
Actual Study Completion Date :
Mar 23, 2021

Arms and Interventions

Arm Intervention/Treatment
Experimental: Palbociclib + Letrozole or Fulvestrant

Drug: Palbociclib + Letrozole or Fulvestrant
Palbociclib x 21 days with a 7 day rest plus 2.5 mg Letrozole QD (no break) or Fulvestrant 500mg IM every 2 weeks for 3 doses and then every 4 weeks until progression or maximum of 12 months
Other Names:
  • Ibrance
  • Femara
  • Faslodex

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Number of Patients Who Complete Planned Oncologic Therapy Without the Development of a Hematological Event [12 months]

      For study purpose febrile neutropenia will be defined according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0: "ANC less than 1000/mm3 with a single temperature of >38.3 degrees Celsius (101 degrees Fahrenheit) or a sustained temperature of 38 degrees Celsius (100.4 degrees Fahrenheit) for more than one hour." Planned oncology therapy is defined as completion of one year of therapy for advanced breast cancer in the absence of disease progression or cessation of study drug due to progressive disease or non-hematological toxicity.

    Secondary Outcome Measures

    1. Dose Delays in Palbociclib Attributed to Neutropenia [12 months]

      Number of patients who required dose delays in palbociclib attributed to neutropenia.

    2. Dose Reductions in Palbociclib Therapy Attributed to Neutropenia [12 months]

      Number of patients who required dose reductions in palbociclib therapy

    3. Clinical Benefit Rate [24 weeks]

      Clinical Benefit Rate (CBR), for those with evaluable disease, defined as the percentage of patients who achieved complete response, partial response and stable disease. RECIST 1.1 was used as the standard way to measure response to treatment. The mean (SD) of specific metabolites were calculated at each time point and graphically assess these measures over time with clinical response and hematological toxicity. The mean change in these variables from baseline to each follow-up point was be calculated. Generalized linear model was utilized for the correlative analysis of clinical response and hematologic events.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    Female
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    1. Self-identified Black, African or African American women of ≥ 18 years of age with proven diagnosis of advanced adenocarcinoma of the breast (locoregionally recurrent or metastatic disease)

    2. ER-positive and/or PgR-positive tumor based on local laboratory results

    3. HER2-negative breast cancer based on local laboratory results (test to be used as per local practice)

    4. Patients must be appropriate candidates for letrozole or fulvestrant therapy

    5. Eastern Cooperative Oncology Group (ECOG) performance status 0-2

    6. Adequate bone marrow function:

    • Absolute Neutrophil Count (ANC) ≥ 1,000/mm3 (1.0 x 109/L);

    • Platelets ≥100,000/mm3 (100 x 109/L);

    • Hemoglobin ≥9 g/dL (90 g/L).

    Exclusion Criteria:

    1. Current use of food or drugs known to be potent inhibitors or inducers of CYP3A4

    2. Active uncontrolled or symptomatic brain metastases. Previously treated and clinically stable, as per Investigator's judgment, brain metastases are permitted.

    3. Previous CDK4/6 inhibitor

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 MedStar Georgetown University Hospital Washington District of Columbia United States 20007
    2 MedStar Washington Hospital Center Washington District of Columbia United States 20013
    3 University of Chicago Chicago Illinois United States 60637
    4 MedStar Union Memorial Hospital Baltimore Maryland United States 21218
    5 MedStar Good Samaritan Hospital Baltimore Maryland United States 21239
    6 Thomas Jefferson University Philadelphia Pennsylvania United States 19107

    Sponsors and Collaborators

    • Georgetown University
    • University of Chicago
    • Thomas Jefferson University

    Investigators

    • Principal Investigator: Claudine Isaacs, MD, MedStar Georgetown University Hospital

    Study Documents (Full-Text)

    More Information

    Publications

    Responsible Party:
    Georgetown University
    ClinicalTrials.gov Identifier:
    NCT02692755
    Other Study ID Numbers:
    • 2015-1396
    First Posted:
    Feb 26, 2016
    Last Update Posted:
    Sep 28, 2021
    Last Verified:
    Aug 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Keywords provided by Georgetown University
    African American
    Additional relevant MeSH terms:
    Breast Neoplasms
    Letrozole
    Fulvestrant
    Palbociclib

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title Palbociclib + Letrozole or Fulvestrant
    Arm/Group Description Palbociclib + Letrozole or Fulvestrant: Palbociclib x 21 days with a 7 day rest plus 2.5 mg Letrozole QD (no break) or Fulvestrant 500mg IM every 2 weeks for 3 doses and then every 4 weeks until progression or maximum of 12 months
    Period Title: Overall Study
    STARTED 35
    COMPLETED 35
    NOT COMPLETED 0

    Baseline Characteristics

    Arm/Group Title Palbociclib + Letrozole or Fulvestrant
    Arm/Group Description Palbociclib + Letrozole or Fulvestrant: Palbociclib x 21 days with a 7 day rest plus 2.5 mg Letrozole QD (no break) or Fulvestrant 500mg IM every 2 weeks for 3 doses and then every 4 weeks until progression or maximum of 12 months
    Overall Participants 35
    Age (Count of Participants)
    <=18 years
    0
    0%
    Between 18 and 65 years
    20
    57.1%
    >=65 years
    15
    42.9%
    Sex: Female, Male (Count of Participants)
    Female
    35
    100%
    Male
    0
    0%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    0
    0%
    Not Hispanic or Latino
    35
    100%
    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
    35
    100%
    White
    0
    0%
    More than one race
    0
    0%
    Unknown or Not Reported
    0
    0%
    Region of Enrollment (participants) [Number]
    United States
    35
    100%
    HR+/HER2- ABC (Count of Participants)
    Count of Participants [Participants]
    35
    100%
    Baseline absolute neutrophil count ≥1000/mm3 (Count of Participants)
    Count of Participants [Participants]
    35
    100%

    Outcome Measures

    1. Primary Outcome
    Title Number of Patients Who Complete Planned Oncologic Therapy Without the Development of a Hematological Event
    Description For study purpose febrile neutropenia will be defined according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0: "ANC less than 1000/mm3 with a single temperature of >38.3 degrees Celsius (101 degrees Fahrenheit) or a sustained temperature of 38 degrees Celsius (100.4 degrees Fahrenheit) for more than one hour." Planned oncology therapy is defined as completion of one year of therapy for advanced breast cancer in the absence of disease progression or cessation of study drug due to progressive disease or non-hematological toxicity.
    Time Frame 12 months

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Palbociclib + Letrozole or Fulvestrant
    Arm/Group Description Palbociclib + Letrozole or Fulvestrant: Palbociclib x 21 days with a 7 day rest plus 2.5 mg Letrozole QD (no break) or Fulvestrant 500mg IM every 2 weeks for 3 doses and then every 4 weeks until progression or maximum of 12 months
    Measure Participants 35
    Count of Participants [Participants]
    35
    100%
    2. Secondary Outcome
    Title Dose Delays in Palbociclib Attributed to Neutropenia
    Description Number of patients who required dose delays in palbociclib attributed to neutropenia.
    Time Frame 12 months

    Outcome Measure Data

    Analysis Population Description
    Including all patients who completed ≥1 treatment cycle
    Arm/Group Title Single ARM
    Arm/Group Description Palbociclib + Letrozole or Fulvestrant Palbociclib + Letrozole or Fulvestrant: Palbociclib x 21 days with a 7 day rest plus 2.5 mg Letrozole QD (no break) or Fulvestrant 500mg IM every 2 weeks for 3 doses and then every 4 weeks until progression or maximum of 12 months
    Measure Participants 33
    Count of Participants [Participants]
    17
    48.6%
    3. Secondary Outcome
    Title Dose Reductions in Palbociclib Therapy Attributed to Neutropenia
    Description Number of patients who required dose reductions in palbociclib therapy
    Time Frame 12 months

    Outcome Measure Data

    Analysis Population Description
    Including all patients who completed ≥1 treatment cycle
    Arm/Group Title Single ARM
    Arm/Group Description Palbociclib + Letrozole or Fulvestrant Palbociclib + Letrozole or Fulvestrant: Palbociclib x 21 days with a 7 day rest plus 2.5 mg Letrozole QD (no break) or Fulvestrant 500mg IM every 2 weeks for 3 doses and then every 4 weeks until progression or maximum of 12 months
    Measure Participants 33
    Count of Participants [Participants]
    13
    37.1%
    4. Secondary Outcome
    Title Clinical Benefit Rate
    Description Clinical Benefit Rate (CBR), for those with evaluable disease, defined as the percentage of patients who achieved complete response, partial response and stable disease. RECIST 1.1 was used as the standard way to measure response to treatment. The mean (SD) of specific metabolites were calculated at each time point and graphically assess these measures over time with clinical response and hematological toxicity. The mean change in these variables from baseline to each follow-up point was be calculated. Generalized linear model was utilized for the correlative analysis of clinical response and hematologic events.
    Time Frame 24 weeks

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Single ARM
    Arm/Group Description Palbociclib + Letrozole or Fulvestrant Palbociclib + Letrozole or Fulvestrant: Palbociclib x 21 days with a 7 day rest plus 2.5 mg Letrozole QD (no break) or Fulvestrant 500mg IM every 2 weeks for 3 doses and then every 4 weeks until progression or maximum of 12 months
    Measure Participants 33
    Count of Participants [Participants]
    23
    65.7%

    Adverse Events

    Time Frame 12 months
    Adverse Event Reporting Description
    Arm/Group Title Single ARM
    Arm/Group Description Palbociclib + Letrozole or Fulvestrant Palbociclib + Letrozole or Fulvestrant: Palbociclib x 21 days with a 7 day rest plus 2.5 mg Letrozole QD (no break) or Fulvestrant 500mg IM every 2 weeks for 3 doses and then every 4 weeks until progression or maximum of 12 months
    All Cause Mortality
    Single ARM
    Affected / at Risk (%) # Events
    Total 1/35 (2.9%)
    Serious Adverse Events
    Single ARM
    Affected / at Risk (%) # Events
    Total 8/35 (22.9%)
    Cardiac disorders
    Heart failure 1/35 (2.9%) 1
    Gastrointestinal disorders
    Colitis 1/35 (2.9%) 1
    Diarrhea 1/35 (2.9%) 1
    General disorders
    Fever 1/35 (2.9%) 1
    Infections and infestations
    Upper respiratory infection 1/35 (2.9%) 1
    Urinary tract infection 1/35 (2.9%) 1
    Investigations
    Neutrophil count decreased 1/35 (2.9%) 1
    Metabolism and nutrition disorders
    Anorexia 1/35 (2.9%) 1
    Psychiatric disorders
    Suicidal ideation 1/35 (2.9%) 1
    Renal and urinary disorders
    Acute kidney injury 1/35 (2.9%) 1
    Respiratory, thoracic and mediastinal disorders
    Respiratory, thoracic and mediastinal disorders 1/35 (2.9%) 1
    Respiratory, thoracic and mediastinal disorders 1/35 (2.9%) 1
    Respiratory, thoracic and mediastinal disorders 1/35 (2.9%) 1
    Vascular disorders
    Hematoma 1/35 (2.9%) 1
    Thromboembolic event 1/35 (2.9%) 1
    Other (Not Including Serious) Adverse Events
    Single ARM
    Affected / at Risk (%) # Events
    Total 32/35 (91.4%)
    Blood and lymphatic system disorders
    Anemia 12/35 (34.3%) 20
    Febrile neutropenia 2/35 (5.7%) 9
    Gastrointestinal disorders
    Abdominal Pain 6/35 (17.1%) 8
    Constipation 4/35 (11.4%) 4
    Diarrhea 3/35 (8.6%) 3
    Nausea 5/35 (14.3%) 5
    General disorders
    Edema limbs 2/35 (5.7%) 2
    Fatigue 16/35 (45.7%) 21
    Flu like symptoms 3/35 (8.6%) 3
    Pain 4/35 (11.4%) 6
    Infections and infestations
    Upper respiratory infection 2/35 (5.7%) 2
    Investigations
    Alkaline Phosphate Increased 3/35 (8.6%) 3
    Aspartate aminotransferase increased 2/35 (5.7%) 2
    Creatinine increased 2/35 (5.7%) 7
    Neutrophil count decreased 17/35 (48.6%) 51
    Platelet count decreased 4/35 (11.4%) 6
    White blood cell decreased 10/35 (28.6%) 41
    Metabolism and nutrition disorders
    Anorexia 4/35 (11.4%) 4
    Hyperglycemia 2/35 (5.7%) 3
    Musculoskeletal and connective tissue disorders
    Arthralgia 3/35 (8.6%) 5
    Myalgia 4/35 (11.4%) 4
    Pain in extremity 2/35 (5.7%) 3
    Nervous system disorders
    Paresthesia 2/35 (5.7%) 2
    Peripheral sensory neuropathy 2/35 (5.7%) 2
    Psychiatric disorders
    Insomnia 2/35 (5.7%) 2
    Respiratory, thoracic and mediastinal disorders
    Cough 4/35 (11.4%) 5
    Skin and subcutaneous tissue disorders
    Rash acneiform 2/35 (5.7%) 2
    Rash maculo-papular 2/35 (5.7%) 2
    Vascular disorders
    Hot flashes 6/35 (17.1%) 6
    Hypertension 2/35 (5.7%) 2

    Limitations/Caveats

    [Not Specified]

    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.

    Results Point of Contact

    Name/Title Nicole Swanson
    Organization Georgetown University
    Phone 2026879194
    Email ns1209@georgetown.edu
    Responsible Party:
    Georgetown University
    ClinicalTrials.gov Identifier:
    NCT02692755
    Other Study ID Numbers:
    • 2015-1396
    First Posted:
    Feb 26, 2016
    Last Update Posted:
    Sep 28, 2021
    Last Verified:
    Aug 1, 2021