Comparing Oral Drug Dosing Strategies in Older Patients With Metastatic Breast Cancer to Maximize Tolerance and Reduce Discontinuation: The CDK4/6 Inhibitor Dosing Knowledge (CDK) Study
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 500
- 试验地点
- 118
- 主要终点
- Time to Treatment Discontinuation (TTD)
研究概览
简要总结
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.
详细描述
The CDK4/6 Inhibitor Dosing Knowledge Study (CDK Study) will study CDK4/6 inhibitor dosing regimens in patients 60 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 (> 60 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 (60-64 years vs. 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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 60 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
- •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.
排除标准
- •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.
- •Concurrent therapy with other investigational agents or anticancer therapy beyond aromatase inhibitors or fulvestrant. Note: radiation is allowed at any time.
- •Rapidly progressive brain metastases. Note: only applies to patients with known brain metastases. Brain imaging not required for enrollment.
- •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.
研究组 & 干预措施
Arm 2: Titrated Dose
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.
干预措施: Ribociclib (Drug)
Arm 1: Indicated Dose
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).
干预措施: Ribociclib 600mg (Drug)
Arm 1: Indicated Dose
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).
干预措施: Palbociclib 125mg (Drug)
Arm 2: Titrated Dose
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.
干预措施: Palbociclib (Drug)
结局指标
主要结局
Time to Treatment Discontinuation (TTD)
时间窗: 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
次要结局
- Body Mass Index(up to 48 months)
- Treatment received (missed doses, cumulative dose, etc.)(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)
- Toxicity (grade 3-4 AEs)(up to 48 months)
- Event-Free survival (EFS)(up to 48 months)
- Healthcare utilization (ED visits, hospital admissions, etc.)(up to 48 months)