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

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

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.

Why it matters

Who can join: the full rules

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 60 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 60 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 or anticancer therapy beyond aromatase inhibitors or fulvestrant. Note: radiation is allowed at any time.
6. Rapidly progressive brain metastases. Note: only applies to patients with known brain metastases. Brain imaging not required for enrollment.
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 it's running

• Ironwood Cancer & Research Centers
  Chandler, Arizona, United States Recruiting
• Ironwood Cancer & Research Centers
  Gilbert, Arizona, United States Recruiting
• Ironwood Cancer & Research Centers
  Glendale, Arizona, United States Recruiting
• Ironwood Cancer & Research Centers
  Goodyear, Arizona, United States Recruiting
• Ironwood Cancer & Research Centers
  Mesa, Arizona, United States Recruiting
• Ironwood Cancer & Research Centers
  Mesa, Arizona, United States Recruiting

+42 more sites. See ClinicalTrials.gov for the full list.

Study contacts

• Principal investigator: Julie Gralow, MD — American Society of Clinical Oncology
• Study coordinator: Jackie Perez, MPH
• Email: CDKstudy@asco.org
• Phone: 571-483-1300

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How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.