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Alternative dosing strategy for CDK4/6 inhibitors in older patients with metastatic breast cancer

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

PHASE3 · American Society of Clinical Oncology · NCT06377852

This study is testing a new way to give CDK4/6 inhibitors to older patients with metastatic breast cancer to see if starting with a lower dose helps them stay on treatment longer and feel better.

Quick facts

PhasePHASE3
Study typeInterventional
Enrollment500 (estimated)
Ages65 Years and up
SexAll
SponsorAmerican Society of Clinical Oncology (other)
Locations67 sites (Chandler, Arizona and 66 other locations)
Trial IDNCT06377852 on ClinicalTrials.gov

What this trial studies

This study aims to evaluate a new dosing strategy for CDK4/6 inhibitors, specifically palbociclib and ribociclib, in patients aged 65 and older with hormone receptor-positive, HER2-negative metastatic breast cancer. It compares the standard full dosing regimen with a titrated approach that starts at a lower dose and increases as tolerated. The primary goal is to determine which dosing strategy allows patients to remain on treatment longer, thereby maximizing the clinical benefits of these medications. The study also includes sub-group analyses based on age and frailty to personalize treatment decisions.

Who should consider this trial

Good fit: Ideal candidates are patients aged 65 years or older with hormone receptor-positive, HER2-negative metastatic breast cancer who are candidates for endocrine therapy.

Not a fit: Patients with non-hormone receptor-positive or HER2-positive metastatic breast cancer may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could help older patients tolerate treatment better and stay on therapy longer, improving their overall outcomes.

How similar studies have performed: Previous studies have shown promise with CDK4/6 inhibitors, but this titrated dosing approach is relatively novel.

Eligibility criteria

Show full inclusion / exclusion criteria 
Inclusion Criteria:

1. 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.
2. 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.
3. Aged 65 years or older
4. Adequate bone marrow and organ function. Laboratory values must be within normal institutional limits, or within ranges as indicated below, or demonstrate minor abnormalities that are deemed clinically non-significant by the investigator.

   * Absolute neutrophil count ≥ 1,000/µL
   * 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.
5. Baseline QTc ≤ 480 ms (only for ribociclib patients)
6. Ability to understand and the willingness to provide informed consent. Note: Remote consent is allowed per institutional guidelines.

Exclusion Criteria:

1. 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.
2. Received greater than 30 days (in the metastatic setting) of the specific endocrine therapy agent planned as partner to the CDK4/6 inhibitor in the study at the time of randomization.
3. Known history of intolerance or allergy to the planned agents used in this trial.
4. Uncontrolled intercurrent illness that, as evaluated by the treating clinician, would hinder compliance with study requirements.
5. Concurrent therapy with other investigational agents.
6. Rapidly progressive brain metastases.
7. 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.
8. Current use of drugs that have known potential to prolong the QT interval (e.g., antiarrhythmic drugs), for patients on ribociclib. Note: If concomitant use cannot be avoided, monitor ECG when initiating, during concomitant use, and as clinically indicated. Refer to crediblemeds.org as a resource.
9. Prior or concurrent malignancies that are undergoing active treatment.

Where this trial is running

Chandler, Arizona and 66 other locations

+17 more sites — see ClinicalTrials.gov for the full list.

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.

View on ClinicalTrials.gov →

Conditions: Metastatic Breast Cancer, MBC

Last reviewed 2026-05-15 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.