Hormone Receptor Positive HER-2 Negative Breast Cancer
Conditions
Keywords
African American
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
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.
Interventions
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
Sponsors
University of Chicago
Thomas Jefferson University
Georgetown University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
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 \-
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| Dose Delays in Palbociclib Attributed to Neutropenia | 12 months | Number of patients who required dose delays in palbociclib attributed to neutropenia. |
| Dose Reductions in Palbociclib Therapy Attributed to Neutropenia | 12 months | Number of patients who required dose reductions in palbociclib therapy |
| 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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 | 35 |
| Total | 35 |
Baseline characteristics
| Characteristic | Palbociclib + Letrozole or Fulvestrant |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 15 Participants |
| Age, Categorical Between 18 and 65 years | 20 Participants |
| Baseline absolute neutrophil count ≥1000/mm3 | 35 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 35 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| HR+/HER2- ABC | 35 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 35 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 0 Participants |
| Region of Enrollment United States | 35 participants |
| Sex: Female, Male Female | 35 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 1 / 35 |
| other Total, other adverse events | 32 / 35 |
| serious Total, serious adverse events | 8 / 35 |
Outcome results
Primary
Number of Patients Who Complete Planned Oncologic Therapy Without the Development of a Hematological Event
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
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Palbociclib + Letrozole or Fulvestrant | Number of Patients Who Complete Planned Oncologic Therapy Without the Development of a Hematological Event | 35 Participants |
Secondary
Clinical Benefit Rate
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
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Palbociclib + Letrozole or Fulvestrant | Clinical Benefit Rate | 23 Participants |
Secondary
Dose Delays in Palbociclib Attributed to Neutropenia
Number of patients who required dose delays in palbociclib attributed to neutropenia.
Time frame: 12 months
Population: Including all patients who completed ≥1 treatment cycle
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Palbociclib + Letrozole or Fulvestrant | Dose Delays in Palbociclib Attributed to Neutropenia | 17 Participants |
Secondary
Dose Reductions in Palbociclib Therapy Attributed to Neutropenia
Number of patients who required dose reductions in palbociclib therapy
Time frame: 12 months
Population: Including all patients who completed ≥1 treatment cycle
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Palbociclib + Letrozole or Fulvestrant | Dose Reductions in Palbociclib Therapy Attributed to Neutropenia | 13 Participants |