Comparing Oral Drug Dosing Strategies in Older Patients with Metastatic Breast Cancer to Maximize Tolerance and Reduce Discontinuation: the CDK4/6 Inhibitor Dosing Knowledge (CDK) Study
65 Years and older (Older Adult ), Male and Female
Summary
The purpose of this study is to generate evidence on an alternative dosing strategy for CDK4/6 inhibitors to help more patients with Metastatic Breast Cancer (MBC) (age ≥ 65 years) tolerate side effects and stay on treatment longer, to derive the most clinical benefit from these drugs
Objectives
The primary objective of the CDK Study is to compare time to treatment discontinuation (TTD) on the approved dosing for palbociclib (125 mg orally daily on days 1-21 of 28-day cycle) or ribociclib (600 mg orally daily on days 1-21 of 28-day cycle) vs. TTD using titrated dosing approach with the same schedule but starting at a lower dose of palbociclib (100 mg or 75 mg) or ribociclib (400 mg or 200 mg) and escalating the dose if well-tolerated in combination with provider/patient choice endocrine therapy (aromatase inhibitor (AI) or fulvestrant) in patients age 65 or older with HR+/HER2- MBC. The secondary and exploratory objectives will generate evidence needed to personalize treatment decisions by comparing patient-centric secondary outcomes and evaluating baseline factors.
Eligibility
- Hormone receptor positive (HR+) HER2 negative metastatic breast cancer. Cut-off values for positive/negative staining should be as per standard practice in accordance with ASCO/CAP (American Society of Clinical Oncology/College of American Pathologists) guidelines. Verification of histology is preferred at the time of recurrence and where not possible or necessary in the judgment of the treating physician, the study will accept histology from the initial diagnosis.
- Candidate for planned endocrine therapy in combination with 1st use of palbociclib or ribociclib, in the metastatic setting. The planned endocrine partner can be an aromatase inhibitor (letrozole, anastrozole, exemestane) or fulvestrant, selected through patient/provider choice.
- Aged 65 years or older
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Adequate bone marrow and organ function.
- Absolute neutrophil count ≥ 1,000/µL
- Platelets ≥ 100,000/µL
- Hemoglobin ≥ 9g/dL
- Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN) (participants with documented Gilbert's disease are allowed total bilirubin up to 5X ULN)
- AST (SGOT)/ALT (SGPT) <3 x institutional ULN, or ≤ 5 x ULN for subjects with documented metastatic disease to the liver.
- Creatinine ≤ institutional ULN or creatinine clearance ≥ 30 mL/min/1.73 m2 for subjects with creatinine levels above institutional ULN.
- Baseline QTc ≤ 480 ms (only for ribociclib patients)
- Ability to understand and the willingness to sign a written informed consent document.
Exclusion Criteria:
- Previous treatment with a CDK4/6 inhibitor for metastatic breast cancer, or previous treatment within the past 12 months with a CDK4/6 inhibitor in the neo/adjuvant breast cancer setting.
- May have received no more than 30 days of the endocrine therapy agent planned as the partner to the CDK4/6 inhibitor in the study.
- Known history of intolerance or allergy to the planned agents used in this trial.
- Uncontrolled intercurrent illness that, as evaluated by the treating clinician, would hinder compliance with study requirements.
- Concurrent therapy with other investigational agents.
- Rapidly progressive brain metastases.
- Active or chronic Hepatitis B or C are eligible provided they meet liver function laboratory criteria and are not on medication with a known interaction with the study agents.
9. Current use of drugs known to prolong the QT interval. 10. Prior or concurrent malignancies that are undergoing active treatment.
Treatment Sites in Georgia
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