The CDK4/6 Inhibitor Dosing Knowledge (CDK) Study

Phase 3

Recruiting

• Conditions: Metastatic Breast Cancer
• Interventions: Drug: Palbociclib 125mg; Drug: Ribociclib; Drug: Ribociclib 600mg; Drug: Palbociclib

• 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.
...

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 (pa...

Basic Information
|
Recruitment & Eligibility
|
Study & Design
|
Trial Locations

Study Timeline

• Study First Submitted: 2024-04-08
• Study First Submitted QC: 2024-04-17
• Study First Posted: 2024-04-22
• Study Start: 2024-10-29
• Status Verified: 2024-11
• Last Update Submitted: 2024-11-26
• Last Update Posted: 2024-11-28
• Primary Completion: 2028-08-31
• Study Completion: 2028-09-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 500

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.

   • 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)

5. Ability to understand and the willingness to sign a written informed consent document.

Read More

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. 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.

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 known to prolong the QT interval. 10. Prior or concurrent malignancies that are undergoing active treatment.

Read More

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 (7)

Dana-Farber Cancer Institute; 🇺🇸 Boston, Massachusetts, 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

Ironwood Cancer & Research Centers; 🇺🇸 Scottsdale, Arizona, United States

Miami Cancer Institute; 🇺🇸 Plantation, Florida, United States

Lewis Cancer and Research Pavilion; 🇺🇸 Savannah, Georgia, United States

The University of New Mexico Comprehensive Cancer Center; 🇺🇸 Albuquerque, New Mexico, United States