The CDK4/6 Inhibitor Dosing Knowledge (CDK) Study
- Conditions
- Metastatic Breast Cancer
- Interventions
- Registration Number
- NCT06377852
- Lead Sponsor
- American Society of Clinical Oncology
- Brief 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.
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.
Together with their treating physician, participants will choose the CDK4/6 inhibitor (palbociclib or ribociclib) and which endocrine therapy (aromatase inhibitor or fulvestrant) of their choice but will be randomized to either Arm 1 (indicated dosing) or Arm 2 (titrated dosing).
- Detailed Description
The CDK4/6 Inhibitor Dosing Knowledge Study (CDK Study) will study CDK4/6 inhibitor dosing regimens in patients 65 or older with Metastatic Breast Cancer (MBC). The overarching goal of this pragmatic, randomized trial is to compare an "indicated" dosing approach, as listed on the FDA-approved drug label, that starts at the full dose of a CDK4/6 inhibitor (palbociclib or ribociclib) with dose reduction based on tolerability versus a "titrated" dosing approach that starts at a lower dose of a CDK4/6 inhibitor and then titrates up to full dose as tolerated. CDK4/6 inhibitors will be given in combination with endocrine therapy (either an aromatase inhibitor (AI) or fulvestrant) based on the choice of the treating clinician.
The primary endpoint will be time to treatment discontinuation (TTD), defined as the time from randomization to last dose of the CDK4/6 inhibitor. The hypothesis is that starting low and escalating as tolerated will help older patients (\> 65 years) stay on therapy longer. Eligibility criteria are broad to allow patients who are not typically included in clinical trials to participate, allowing for a more representative sample of participants. The investigators will conduct sub-group analyses based on age (65-74 years vs. ≥75 years) and baseline frailty scores. This study builds upon the lessons learned from prior studies with CDK4/6 inhibitors. The investigators will augment the standard assessment of treatment toxicities assessed by the health care team with prospectively collected patient-reported outcomes data to better reflect how participants tolerate the different dosing approaches.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 500
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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.
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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.
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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)
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Ability to understand and the willingness to sign a written informed consent document.
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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.
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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.
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Known history of intolerance or allergy to the planned agents used in this trial.
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Uncontrolled intercurrent illness that, as evaluated by the treating clinician, would hinder compliance with study requirements.
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Concurrent therapy with other investigational agents.
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Rapidly progressive brain metastases.
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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.
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Current use of drugs known to prolong the QT interval. 10. Prior or concurrent malignancies that are undergoing active treatment.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm 1: Indicated Dose Palbociclib 125mg Arm 1 of the study is the indicated dosing regimen, provided in the FDA approved drug label: participants will start cycle 1 with either 125mg dose of palbociclib or 600mg dose of ribociclib, in combination with endocrine therapy (AI or fulvestrant). Arm 1: Indicated Dose Ribociclib 600mg Arm 1 of the study is the indicated dosing regimen, provided in the FDA approved drug label: participants will start cycle 1 with either 125mg dose of palbociclib or 600mg dose of ribociclib, in combination with endocrine therapy (AI or fulvestrant). Arm 2: Titrated Dose Ribociclib Arm 2 is the titrated dosing regimen: participants will start cycle 1 with either 100 mg or 75 mg dose of palbociclib or 400 mg or 200 mg dose of ribociclib, in combination with endocrine therapy (AI or fulvestrant). For cycle 2 and for subsequent cycles, escalation to the indicated dose will be based on treatment tolerance. Arm 2: Titrated Dose Palbociclib Arm 2 is the titrated dosing regimen: participants will start cycle 1 with either 100 mg or 75 mg dose of palbociclib or 400 mg or 200 mg dose of ribociclib, in combination with endocrine therapy (AI or fulvestrant). For cycle 2 and for subsequent cycles, escalation to the indicated dose will be based on treatment tolerance.
- Primary Outcome Measures
Name Time Method Time to Treatment Discontinuation (TTD) up to 48 months Our primary outcome is time to CDK4/6 inhibitor discontinuation (TTD): the number of days between randomization and the last day the patient takes any dose of the same CDK4/6 inhibitor (regardless of drug holds, dose changes
- Secondary Outcome Measures
Name Time Method Body Mass Index up to 48 months weight and height will be combined to report BMI in kg/m\^2
Treatment received (missed doses, cumulative dose, etc.) up to 48 months Assessed in each arm of the study and study drug
Reason for not escalating up to 48 months Assessed in each arm of the study and study drug
Quality of life assessed by patient reported outcomes up to 48 months PROMIS-29 (3 domains of 12 questions, physical function, fatigue, participation in social activities), FACT-G Item GP5 (1 question)
Time to dose reduction and escalation up to 48 months For titrated arm. Assessed in each arm of the study and study drug
Toxicity (grade 3-4 AEs) up to 48 months Assessed in each arm of the study and study drug
Event-Free survival (EFS) up to 48 months Assessed in each arm of the study and study drug
Healthcare utilization (ED visits, hospital admissions, etc.) up to 48 months ED visits, hospital admissions, etc., assessed in each arm of the study and study drug
Trial Locations
- Locations (42)
Ironwood Cancer & Research Centers
🇺🇸Scottsdale, Arizona, United States
University of Colorado Anschutz Medical Campus
🇺🇸Aurora, Colorado, United States
Smilow Cancer Hospital Care Center - Derby
🇺🇸Derby, Connecticut, United States
Smilow Cancer Hospital Care Center - Fairfield
🇺🇸Fairfield, Connecticut, United States
Smilow Cancer Hospital at Glastonbury
🇺🇸Glastonbury, Connecticut, United States
Smilow Cancer Hospital Care Center - Greenwich
🇺🇸Greenwich, Connecticut, United States
Smilow Cancer Hospital Care Center - Guilford
🇺🇸Guilford, Connecticut, United States
Smilow Cancer Hospital at Saint Francis
🇺🇸Hartford, Connecticut, United States
Yale University/Yale Cancer Center
🇺🇸New Haven, Connecticut, United States
Smilow Cancer Hospital Care Center - North Haven
🇺🇸North Haven, Connecticut, United States
Smilow Cancer Hospital Care Center - Torrington
🇺🇸Torrington, Connecticut, United States
Smilow Cancer Hospital Care Center - Trumbull
🇺🇸Trumbull, Connecticut, United States
Smilow Cancer Hospital Care Center - Waterbury
🇺🇸Waterbury, Connecticut, United States
Smilow Cancer Hospital - Waterford
🇺🇸Waterford, Connecticut, United States
Miami Cancer Institute
🇺🇸Plantation, Florida, United States
Emory University Winship Cancer Institute
🇺🇸Atlanta, Georgia, United States
Lewis Cancer and Research Pavilion
🇺🇸Savannah, Georgia, United States
The University of Kansas Cancer Center
🇺🇸Westwood, Kansas, United States
The Jackson Laboratory (JAX) - Harold Alfond Center for Cancer Care
🇺🇸Augusta, Maine, United States
The Jackson Laboratory (JAX) - Northern Light Cancer Care
🇺🇸Brewer, Maine, United States
Dana-Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
Dana-Farber Brigham Cancer Center Foxborough
🇺🇸Foxboro, Massachusetts, United States
Dana-Farber Cancer Institute Merrimack Valley
🇺🇸Methuen, Massachusetts, United States
Dana-Farber Brigham Cancer Center at Milford Regional Medical Center
🇺🇸Milford, Massachusetts, United States
Dana-Farber Brigham Cancer Center at South Shore Health
🇺🇸Weymouth, Massachusetts, United States
Dana-Farber/New Hampshire Oncology-Hematology
🇺🇸Londonderry, New Hampshire, United States
Penn Medicine - Princeton Health
🇺🇸Plainsboro, New Jersey, United States
Lovelace Medical Center - Saint Joseph Square
🇺🇸Albuquerque, New Mexico, United States
Lovelace Women's Hospital
🇺🇸Albuquerque, New Mexico, United States
Presbyterian Kaseman Hospital
🇺🇸Albuquerque, New Mexico, United States
The University of New Mexico Comprehensive Cancer Center
🇺🇸Albuquerque, New Mexico, United States
Memorial Medical Center
🇺🇸Las Cruces, New Mexico, United States
Presbyterian Rust Medical Center/Jorgensen Cancer Center
🇺🇸Rio Rancho, New Mexico, United States
Levine Cancer Institute
🇺🇸Rock Hill, South Carolina, United States
Penn Medicine - Lancaster General Hospital
🇺🇸Lancaster, Pennsylvania, United States
Penn Medicine - Perelman Center for Advanced Medicine
🇺🇸Philadelphia, Pennsylvania, United States
Penn Medicine - Pennsylvania Hospital
🇺🇸Philadelphia, Pennsylvania, United States
Penn Medicine - Chester County Hospital
🇺🇸West Chester, Pennsylvania, United States
Smilow Cancer Hospital - Westerly
🇺🇸Westerly, Rhode Island, United States
St. Joseph's Candler Bluffton Campus
🇺🇸Bluffton, South Carolina, United States
SC Cancer Specialists - Hilton Head at St. Joseph's/Candler
🇺🇸Hilton Head Island, South Carolina, United States
Baptist Memorial Healthcare
🇺🇸Memphis, Tennessee, United States