Trial Title:
The CDK4/6 Inhibitor Dosing Knowledge (CDK) Study
NCT ID:
NCT06377852
Condition:
Metastatic Breast Cancer
Conditions: Official terms:
Breast Neoplasms
Palbociclib
Conditions: Keywords:
MBC
Study type:
Interventional
Study phase:
Phase 3
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Intervention model description:
500 patients will be enrolled, 250 per arm (Arm 1 being indicated dose, Arm 2 being
titrated dose).
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Palbociclib 125mg
Description:
Arm 1: Indicated dosing for palbociclib (125 mg orally daily on days 1-21 of 28-day
cycle)
Arm group label:
Arm 1: Indicated Dose
Intervention type:
Drug
Intervention name:
Ribociclib 600mg
Description:
Arm 1: Indicated dosing of ribociclib (600 mg orally daily on days 1-21 of 28-day cycle)
Arm group label:
Arm 1: Indicated Dose
Intervention type:
Drug
Intervention name:
Ribociclib
Description:
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 group label:
Arm 2: Titrated Dose
Intervention type:
Drug
Intervention name:
Palbociclib
Description:
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 group label:
Arm 2: Titrated Dose
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).
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 (palbociclib or ribociclib) with dose reduction based on tolerability
versus a "titrated" dosing approach that starts at a lower dose of a CDK4/6 inhibitor and
then titrates up to full dose as tolerated. CDK4/6 inhibitors will be given in
combination with endocrine therapy (either an aromatase inhibitor (AI) or fulvestrant)
based on the choice of the treating clinician.
The primary endpoint will be time to treatment discontinuation (TTD), defined as the time
from randomization to last dose of the CDK4/6 inhibitor. The hypothesis is that starting
low and escalating as tolerated will help older patients (> 65 years) stay on therapy
longer. Eligibility criteria are broad to allow patients who are not typically included
in clinical trials to participate, allowing for a more representative sample of
participants. The investigators will conduct sub-group analyses based on age (65-74 years
vs. ≥75 years) and baseline frailty scores. This study builds upon the lessons learned
from prior studies with CDK4/6 inhibitors. The investigators will augment the standard
assessment of treatment toxicities assessed by the health care team with prospectively
collected patient-reported outcomes data to better reflect how participants tolerate the
different dosing approaches.
Criteria for eligibility:
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.
- 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.
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.
9. Current use of drugs known to prolong the QT interval. 10. Prior or concurrent
malignancies that are undergoing active treatment.
Gender:
All
Minimum age:
65 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Ironwood Cancer & Research Centers
Address:
City:
Chandler
Zip:
85224
Country:
United States
Status:
Recruiting
Contact:
Last name:
Berenice Valdez
Phone:
480-890-7705
Email:
berenice.mendez@ironwoodcrc.com
Investigator:
Last name:
Sumeet Mendonca, MD
Email:
Principal Investigator
Facility:
Name:
Ironwood Cancer & Research Centers
Address:
City:
Gilbert
Zip:
85297
Country:
United States
Status:
Recruiting
Contact:
Last name:
Berenice Valdez
Phone:
480-890-7705
Email:
berenice.mendez@ironwoodcrc.com
Investigator:
Last name:
Sumeet Mendonca, MD
Email:
Principal Investigator
Facility:
Name:
Ironwood Cancer & Research Centers
Address:
City:
Glendale
Zip:
85306
Country:
United States
Status:
Recruiting
Contact:
Last name:
Berenice Valdez
Phone:
480-890-7705
Email:
berenice.mendez@ironwoodcrc.com
Investigator:
Last name:
Sumeet Mendonca, MD
Email:
Principal Investigator
Facility:
Name:
Ironwood Cancer & Research Centers
Address:
City:
Mesa
Zip:
85202
Country:
United States
Status:
Recruiting
Contact:
Last name:
Berenice Valdez
Phone:
480-890-7705
Email:
berenice.mendez@ironwoodcrc.com
Investigator:
Last name:
Sumeet Mendonca, MD
Email:
Principal Investigator
Facility:
Name:
Ironwood Cancer & Research Centers
Address:
City:
Mesa
Zip:
85206
Country:
United States
Status:
Recruiting
Contact:
Last name:
Berenice Valdez
Phone:
480-890-7705
Email:
berenice.mendez@ironwoodcrc.com
Investigator:
Last name:
Sumeet Mendonca, MD
Email:
Principal Investigator
Facility:
Name:
Ironwood Cancer & Research Centers
Address:
City:
Phoenix
Zip:
85028
Country:
United States
Status:
Recruiting
Contact:
Last name:
Berenice Valdez
Phone:
480-890-7705
Email:
berenice.mendez@ironwoodcrc.com
Investigator:
Last name:
Sumeet Mendonca, MD
Email:
Principal Investigator
Facility:
Name:
Ironwood Cancer & Research Centers
Address:
City:
Scottsdale
Zip:
85260
Country:
United States
Status:
Recruiting
Contact:
Last name:
Berenice Valdez
Phone:
480-890-7705
Email:
berenice.mendez@ironwoodcrc.com
Investigator:
Last name:
Sumeet Mendonca, MD
Email:
Principal Investigator
Facility:
Name:
Miami Cancer Institute
Address:
City:
Miami
Zip:
33176
Country:
United States
Status:
Recruiting
Contact:
Last name:
Elaine Hernandez
Phone:
786-527-8537
Email:
elaineher@baptisthealth.net
Investigator:
Last name:
Reshma Mahtani, DO
Email:
Principal Investigator
Facility:
Name:
Miami Cancer Institute
Address:
City:
Plantation
Zip:
33324
Country:
United States
Status:
Recruiting
Contact:
Last name:
Krystal Fernandez
Phone:
954-837-1566
Email:
Krystal.Fernandez@baptisthealth.net
Investigator:
Last name:
Reshma Mahtani, DO
Email:
Principal Investigator
Start date:
October 29, 2024
Completion date:
September 1, 2028
Lead sponsor:
Agency:
American Society of Clinical Oncology
Agency class:
Other
Collaborator:
Agency:
Patient-Centered Outcomes Research Institute
Agency class:
Other
Source:
American Society of Clinical Oncology
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06377852
