Testing the Addition of Radium Therapy (Radium-223 Dichloride) to the Usual Chemotherapy Treatment (Paclitaxel) for Advanced Breast Cancer That Has Spread to the Bones
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT04090398|
Recruitment Status : Recruiting
First Posted : September 16, 2019
Last Update Posted : October 5, 2021
|Condition or disease||Intervention/treatment||Phase|
|Anatomic Stage IV Breast Cancer AJCC v8 Hormone Receptor-Positive Breast Carcinoma Metastatic Breast Carcinoma Metastatic HER2-Negative Breast Carcinoma Metastatic Malignant Neoplasm in the Bone Metastatic Triple-Negative Breast Carcinoma Prognostic Stage IV Breast Cancer AJCC v8||Drug: Paclitaxel Radiation: Radium Ra 223 Dichloride||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||70 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase II Trial of Radium-223 Dichloride in Combination With Paclitaxel in Patients With Bone Metastatic Breast Cancer|
|Actual Study Start Date :||December 27, 2019|
|Estimated Primary Completion Date :||June 30, 2022|
|Estimated Study Completion Date :||June 30, 2022|
Experimental: Arm I (paclitaxel, radium Ra 223 dichloride)
Patients receive paclitaxel IV over 1 hour on days 1, 8, and 15 and radium Ra 223 dichloride IV over 1 minute on day 1. Treatment with radium Ra 223 dichloride repeats every 28 days for 6 cycles and treatment with paclitaxel repeats every 28 days in the absence of disease progression or unacceptable toxicity.
Radiation: Radium Ra 223 Dichloride
Active Comparator: Arm II (paclitaxel)
Patients receive paclitaxel IV over 1 hour on days 1, 8, and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
- Progression-free survival (PFS) [ Time Frame: From randomization to the first documented tumor progression or death due to any cause, whichever occurred first, assessed up to 2 years ]Tumor progression will be determined from radiographic scans performed every 8 weeks (computed tomography and bone scan) using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria. The log-rank test will be used to analyze PFS for comparison of treatment effects, i.e., the only covariate that will be used is the treatment arm. Distributions of PFS times will be estimated using the Kaplan-Meier product-limit method.
- PFS [ Time Frame: From randomization to the first documented tumor progression or death due to any cause, whichever occurred first, assessed up to 2 years ]Treatment comparison in PFS will be conducted in pre-defined subgroups, including hormone receptor status and presence/absence of visceral metastases and two-sided 80% confidence intervals (CIs) will be provided for each subgroup.
- Time to first symptomatic skeletal event (SSE) [ Time Frame: Time from randomization to the occurrence of the first SSE, assessed up to 2 years ]Will be defined as the first use of radiation therapy to relieve skeletal symptoms, new symptomatic pathologic vertebral or non-vertebral bone fractures, spinal cord compression, or tumor-related orthopedic surgical intervention. Distributions of time to SSE will be estimated using the method of Kaplan-Meier and compared between treatment arms using the stratified log-rank test.
- Objective response rate [ Time Frame: From start of treatment until disease progression, assessed up to 2 years ]Will be defined as the proportion of all subjects with confirmed partial response or complete response according to RECIST 1.1.
- Overall survival (OS) [ Time Frame: Time from randomization to death due to any cause, assessed up to 2 years ]The log-rank test will be used as the primary analysis for comparison of treatment effects, i.e., the only covariate that will be used is the treatment arm. Distributions of OS times will be estimated using the Kaplan-Meier product-limit method. The median OS times with two-sided 95% CIs will be estimated for each treatment group.
- Incidence of adverse events (AEs) [ Time Frame: Up to 30 days after end of study treatment ]Will be assessed by grading all treatment-related AEs and events of clinical interest (ECI) according to National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Grade 3 or higher diarrhea or constipation are ECI for the proposed trial. Adverse events will be summarized according to grade, overall and by treatment arm, as number and percentage of participants. All adverse events resulting in discontinuation, dose modification, and/or dosing interruption, and/or treatment delay of drug will also be summarized by treatment arm.
- Fludeoxyglucose F-18 (18F-FDG) positron emission tomography (PET)/computed tomography (CT) response [ Time Frame: Up to day 1 of cycle 4 (each cycle = 28 days) ]Will be measured by PET Response Criteria in Solid Tumors at baseline and after cycle 3 (between treatments on cycle 3, day 15 and cycle 4, day 1). The peak SUL of hottest single tumor lesion with maximal 1.2 - cm diameter volume region of interest (ROI) (SULpeak) will be measured. The longest diameters and SULpeak of target lesions (up to 5 of the hottest lesions) on the PET/CT images before and after treatment will be measured (Wahl et al., 2009). Tumor response by PERCIST will be summarized as number and percentage of participants with complete response, partial response, stable disease, and progressive disease by treatment arm with two-sided 80% CI and compared between groups using Fisher's exact tests.
- Qualitative or semi-quantitative 18F-FDG PET/CT reporting of standardized uptake value (SUV) [ Time Frame: Up to 2 years ]Quantitative imaging biomarkers will be used for 18F-FDG-PET scan analysis as recommended. Two levels of SUV analysis will be performed: lesion level, in which SUV metrics will be extracted from each lesion ROI, and patient level, in which all lesions for a single patient will be grouped into a patient ROI before SUV analysis. Uptake will be quantified with maximal uptake (SUVmax), mean uptake (SUVmean), and total uptake (SUVtotal). For both ROI levels, SUVmax will be defined as the maximum SUV of the ROI and SUVtotal will be defined as the total summed SUV of the ROI normalized to voxel volume. SUVmean will be defined as the mean SUV within the lesion ROI or the mean of the SUVmean of all lesions within the patient ROI. For each SUV metric, response will be calculated as percent change from baseline to mid-treatment scans.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04090398
|Principal Investigator:||Jyoti Malhotra||University Health Network Princess Margaret Cancer Center LAO|