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The CDK4/6 Inhibitor Dosing Knowledge (CDK) Study

ConditionMetastatic Breast Cancer
Trial statusRecruiting
Trial phasePhase 3
Trial typeInterventional
Biological sexAll
Age60+
SponsorAmerican Society of Clinical Oncology

About this trial

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 ≥ 60 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 60 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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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 60 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.

Disqualifiers

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 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.

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.

Trial design

Design model

Parallel

Treatments tested in this trial

  • Palbociclib 125mg

    Drug

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

  • Ribociclib 600mg

    Drug

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

  • Ribociclib

    Drug

    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.

  • Palbociclib

    Drug

    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.

Treatment groups

500 Participants
are divided into 2 treatment groups
Group A: Arm 1: Indicated DoseExperimental treatment 2 interventions
Group B: Arm 2: Titrated DoseExperimental treatment 2 interventions

Trial outcomes

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

Time frame
up to 48 months

Secondary outcomes

1

Toxicity (grade 3-4 AEs)

Assessed in each arm of the study and study drug

Time frame
up to 48 months
2

Event-Free survival (EFS)

Assessed in each arm of the study and study drug

Time frame
up to 48 months
3

Quality of life assessed by patient reported outcomes

PROMIS-29 (3 domains of 12 questions, physical function, fatigue, participation in social activities), FACT-G Item GP5 (1 question)

Time frame
up to 48 months
4

Time to dose reduction and escalation

For titrated arm. Assessed in each arm of the study and study drug

Time frame
up to 48 months

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

American Society of Clinical Oncology

Lead sponsor

Patient-Centered Outcomes Research Institute

Collaborator

Source ClinicalTrials.gov
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