Description:
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
Title
- Brief Title: Palbociclib / Letrozole or Fulvestrant in African American Women With HR+ HER2- Breast Cancer
- 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
Clinical Trial IDs
- ORG STUDY ID:
2015-1396
- NCT ID:
NCT02692755
Conditions
- Hormone Receptor Positive HER-2 Negative Breast Cancer
Interventions
Drug | Synonyms | Arms |
---|
Palbociclib + Letrozole or Fulvestrant | Ibrance, Femara, Faslodex | Palbociclib + Letrozole or Fulvestrant |
Purpose
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.
Trial Arms
Name | Type | Description | Interventions |
---|
Palbociclib + Letrozole or Fulvestrant | Experimental | | - Palbociclib + Letrozole or Fulvestrant
|
Eligibility Criteria
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
-
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | Female |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Number of Patients Who Complete Planned Oncologic Therapy Without the Development of a Hematological Event |
Time Frame: | 12 months |
Safety Issue: | |
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. |
Secondary Outcome Measures
Measure: | Dose Delays in Palbociclib Attributed to Neutropenia |
Time Frame: | 12 months |
Safety Issue: | |
Description: | Number of patients who required dose delays in palbociclib attributed to neutropenia. |
Measure: | Dose Reductions in Palbociclib Therapy Attributed to Neutropenia |
Time Frame: | 12 months |
Safety Issue: | |
Description: | Number of patients who required dose reductions in palbociclib therapy |
Measure: | Clinical Benefit Rate |
Time Frame: | 24 weeks |
Safety Issue: | |
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. 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. |
Details
Phase: | Phase 2/Phase 3 |
Primary Purpose: | Interventional |
Overall Status: | Completed |
Lead Sponsor: | Georgetown University |
Trial Keywords
Last Updated
August 20, 2021