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). Note: Telehealth visits are allowed at any time per institutional guidelines. In addition, the study allows for remote consenting per institutional guidelines.

Trial Health

On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment

500

participants targeted

Target at P50-P75 for phase_3

Timeline

28mo left

Started Oct 2024

Typical duration for phase_3

Geographic Reach

1 country

67 active sites

Status

recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

3.8 years study duration

Study Progress40%

Oct 2024Sep 2028

First Submitted

Initial submission to the registry

April 8, 2024

Completed

14 days until next milestone

First Posted

Study publicly available on registry

April 22, 2024

Completed

6 months until next milestone

Study Start

First participant enrolled

October 29, 2024

Completed

3.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

August 31, 2028

Expected

1 day until next milestone

Study Completion

Last participant's last visit for all outcomes

September 1, 2028

Last Updated

March 18, 2026

Status Verified

March 1, 2026

Enrollment Period

3.8 years

First QC Date

April 8, 2024

Last Update Submit

March 16, 2026

Conditions

Metastatic Breast Cancer

Keywords

MBC

Outcome Measures

Primary Outcomes (1)

Time to Treatment Discontinuation (TTD)
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
up to 48 months

Secondary Outcomes (8)

Toxicity (grade 3-4 AEs)
up to 48 months
Event-Free survival (EFS)
up to 48 months
Quality of life assessed by patient reported outcomes
up to 48 months
Time to dose reduction and escalation
up to 48 months
Reason for not escalating
up to 48 months
+3 more secondary outcomes

Study Arms (2)

Arm 1: Indicated Dose

EXPERIMENTAL

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).

Drug: Palbociclib 125mgDrug: Ribociclib 600mg

Arm 2: Titrated Dose

EXPERIMENTAL

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.

Drug: RibociclibDrug: Palbociclib

Interventions

RibociclibDRUG

Arm 2: Titrated dosing approach with the same schedule but starting at a lower dose of ribociclib (400 mg or 200 mg) and escalating the dose if well-tolerated in combination with provider/patient choice of endocrine therapy.

Arm 2: Titrated Dose

PalbociclibDRUG

Arm 2: Titrated dosing approach with the same schedule but starting at a lower dose of palbociclib (100 mg or 75 mg) and escalating the dose if well-tolerated in combination with provider/patient choice of endocrine therapy.

Arm 2: Titrated Dose

Palbociclib 125mgDRUG

Arm 1: Indicated dosing for palbociclib (125 mg orally daily on days 1-21 of 28-day cycle)

Arm 1: Indicated Dose

Ribociclib 600mgDRUG

Arm 1: Indicated dosing of ribociclib (600 mg orally daily on days 1-21 of 28-day cycle)

Arm 1: Indicated Dose

Eligibility Criteria

Age65 Years+

Sexall

Healthy VolunteersNo

Age GroupsOlder Adult (65+)

You may qualify if:

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
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.
Baseline QTc ≤ 480 ms (only for ribociclib patients)
Ability to understand and the willingness to provide informed consent. Note: Remote consent is allowed per institutional guidelines.

You may not qualify if:

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.
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.
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.
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.
Prior or concurrent malignancies that are undergoing active treatment.

Contact the study team to confirm eligibility.