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
Phase II Trial of Radium-223 Dichloride in Combination With Paclitaxel in Patients With Bone Metastatic Breast Cancer
5 other identifiers
interventional
70
1 country
30
Brief Summary
This phase II trial studies how well radium-223 dichloride and paclitaxel work in treating patients with advanced breast cancer that has spread to the bones. Radium-223 dichloride is a radioactive drug that behaves in a similar way to calcium and collects in cancer that has spread to the bones (bone metastases). The radioactive particles in radium-223 dichloride act on bone metastases, killing the tumor cells and reducing the pain that they can cause. Drugs used in chemotherapy, such as paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving radium-223 dichloride and paclitaxel may work better in treating patients with metastatic breast cancer compared to paclitaxel alone.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_2
Started Aug 2020
Longer than P75 for phase_2
30 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
September 13, 2019
CompletedFirst Posted
Study publicly available on registry
September 16, 2019
CompletedStudy Start
First participant enrolled
August 4, 2020
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 30, 2026
ExpectedStudy Completion
Last participant's last visit for all outcomes
June 30, 2026
April 13, 2026
December 1, 2025
5.9 years
September 13, 2019
April 9, 2026
Conditions
Outcome Measures
Primary Outcomes (1)
Progression-free survival (PFS)
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.
From randomization to the first documented tumor progression or death due to any cause, whichever occurred first, assessed up to 2 years
Secondary Outcomes (5)
PFS
From randomization to the first documented tumor progression or death due to any cause, whichever occurred first, assessed up to 2 years
Time to first symptomatic skeletal event (SSE)
From randomization to the occurrence of the first SSE, assessed up to 2 years
Objective response rate
From start of treatment until disease progression, assessed up to 2 years
Overall survival (OS)
From randomization to death due to any cause, assessed up to 2 years
Incidence of adverse events (AEs)
Up to 30 days after end of study treatment
Other Outcomes (1)
Molecular profiling assays on malignant and normal tissues
At baseline
Study Arms (2)
Arm I (paclitaxel, radium Ra 223 dichloride)
EXPERIMENTALPatients receive paclitaxel IV over 1 hour on days 1, 8, and 15 and radium Ra 223 dichloride IV over 1 minute on day 1 of each cycle. 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. Patients also undergo CT scan, bone scan and/or MRI, as well as collection of blood samples throughout trial. Patients may optionally undergo SPECT on trial.
Arm II (paclitaxel)
ACTIVE COMPARATORPatients receive paclitaxel IV over 1 hour on days 1, 8, and 15 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT scan, bone scan, and/or MRI, as well as collection of blood samples throughout trial. Patients may optionally undergo SPECT on trial.
Interventions
Undergo MRI
Given IV
Given IV
Undergo SPECT
Undergo bone scan
Correlative studies
Undergo CT scan
Ancillary studies
Eligibility Criteria
You may qualify if:
- Women or men with metastatic breast cancer with two or more bone metastases identified by technetium Tc-99m (99mTc) bone scintigraphy and/or CT, at least one of these bone lesions must not have been treated with prior radiation therapy
- A diagnosis of breast cancer must have been histologically or cytologically confirmed at any time point
- Patients with non-bone metastases (in addition to bone metastases) are permitted if:
- Five or less visceral metastasis (=\< 4 cm in size) and asymptomatic (not including lymph nodes)
- Enlarged lymph nodes =\< 4 cm
- Patients with HER2 negative disease (HER2 negativity by immunohistochemistry \[IHC\] or fluorescent in situ hybridization \[FISH\] ratio according to the American Society of Clinical Oncology-College of American Pathologists guideline criteria) (Hammond et al., 2010; Wolff et al., 2013). Hormone-receptor positive (estrogen receptor \[ER\]-positive and/or progesterone receptor \[PR\]-positive) as well as triple-negative (ER-negative, PR-negative and no overexpression of HER2) breast cancer may be enrolled. Hormone receptor status will be determined at the local institution. ER and PR negativity will be defined as \< 1% tumor staining by IHC
- Patient must be eligible to receive therapy with paclitaxel for the treatment of their breast cancer. Patients with hormone-receptor positive disease should have progressed on at least one prior line of hormone therapy and a CDK4/6 inhibitor in the metastatic setting to be eligible (except if patient had a contraindication or intolerable toxicity with the use of these agents). Previous radiation and chemotherapy for the treatment of metastatic breast cancer is allowed
- Age \>= 18 years
- Because no dosing or AE data are currently available on the use of radium-223 dichloride in combination with paclitaxel in patients \< 18 years of age, children are excluded from this study, but will be eligible for future pediatric trials
- Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 (Karnofsky \>= 60%)
- Absolute neutrophil count (ANC) \>= 1,500/mcL
- Platelets \>= 100,000/mcL
- Total bilirubin =\< 1.5 x institutional upper limit of normal (ULN) (with the exception of \< 3 mg/dL for patients with Gilbert's disease)
- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 3 x institutional ULN (=\< 5 ULN for patients with liver metastasis)
- Creatinine =\< 1.5 x institutional ULN OR glomerular filtration rate (GFR) \>= 40 mL/min/1.73 m\^2
- +11 more criteria
You may not qualify if:
- Patients with peripheral neuropathy \> grade 1
- Patients who have not recovered from AEs due to prior anti-cancer therapy (i.e., have residual toxicities \> grade 1) with the exception of alopecia
- Patients who have had chemotherapy or immunotherapy with checkpoint inhibitor within 4 weeks prior to treatment. Patient who receives radiation therapy or hormone therapy within 2 weeks prior to treatment are excluded. For patients on trial therapy prior to study enrollment, washout period of 6 times the half-life of previously administered investigational agents prior to starting radium-223 dichloride is required
- Prior therapy with radionuclides (e.g., strontium, samarium, rhenium, radium)
- Patients who are receiving any other investigational agents. Vaccination for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is allowed as well as any therapy as required for the treatment of active coronavirus disease 2019 (COVID-19) infection
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to radium-223 dichloride or other agents used in study
- Patients with psychiatric illness/social situations that would limit compliance with study requirements
- Pregnant women are excluded from this study because radium-223 dichloride is an alpha particle-emitting radiopharmaceutical agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for AEs in nursing infants secondary to treatment of the mother with radium-223 dichloride, breastfeeding should be discontinued if the mother is treated with radium-223 dichloride. These potential risks may also apply to other agents used in this study
- Imminent/established spinal cord compression, pathological fracture in weight bearing bones or bone lesion with soft tissue component unless treated as appropriate with radiation and/or surgery before starting on trial
- Prior hemibody external radiotherapy
- Patients must not have an active infection requiring systemic treatment
- Patients must not use immunosuppressive medication =\< 7 days of registration, EXCEPT for the following:
- Intranasal, inhaled, topical steroids, or local steroid injection (e.g., intra-articular injection)
- Systemic corticosteroids at physiologic doses =\< 10 mg/day of prednisone or equivalent
- Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication) is allowed
- +5 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (30)
University of Alabama at Birmingham Cancer Center
Birmingham, Alabama, 35233, United States
City of Hope Comprehensive Cancer Center
Duarte, California, 91010, United States
UC Irvine Health/Chao Family Comprehensive Cancer Center
Orange, California, 92868, United States
University of California Davis Comprehensive Cancer Center
Sacramento, California, 95817, United States
UM Sylvester Comprehensive Cancer Center at Coral Gables
Coral Gables, Florida, 33146, United States
UM Sylvester Comprehensive Cancer Center at Deerfield Beach
Deerfield Beach, Florida, 33442, United States
University of Miami Miller School of Medicine-Sylvester Cancer Center
Miami, Florida, 33136, United States
UM Sylvester Comprehensive Cancer Center at Kendall
Miami, Florida, 33176, United States
UM Sylvester Comprehensive Cancer Center at Plantation
Plantation, Florida, 33324, United States
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, 60637, United States
UC Comprehensive Cancer Center at Silver Cross
New Lenox, Illinois, 60451, United States
University of Chicago Medicine-Orland Park
Orland Park, Illinois, 60462, United States
University of Kansas Clinical Research Center
Fairway, Kansas, 66205, United States
University of Kansas Cancer Center
Kansas City, Kansas, 66160, United States
University of Kansas Cancer Center-Overland Park
Overland Park, Kansas, 66210, United States
University of Kansas Health System Saint Francis Campus
Topeka, Kansas, 66606, United States
University of Kansas Hospital-Westwood Cancer Center
Westwood, Kansas, 66205, United States
University of Kentucky/Markey Cancer Center
Lexington, Kentucky, 40536, United States
Wayne State University/Karmanos Cancer Institute
Detroit, Michigan, 48201, United States
Weisberg Cancer Treatment Center
Farmington Hills, Michigan, 48334, United States
University of Kansas Cancer Center - North
Kansas City, Missouri, 64154, United States
University of Kansas Cancer Center - Lee's Summit
Lee's Summit, Missouri, 64064, United States
University of Kansas Cancer Center at North Kansas City Hospital
North Kansas City, Missouri, 64116, United States
Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center
Lebanon, New Hampshire, 03756, United States
Rutgers Cancer Institute of New Jersey
New Brunswick, New Jersey, 08903, United States
Laura and Isaac Perlmutter Cancer Center at NYU Langone
New York, New York, 10016, United States
Wake Forest University Health Sciences
Winston-Salem, North Carolina, 27157, United States
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43210, United States
University of Pittsburgh Cancer Institute (UPCI)
Pittsburgh, Pennsylvania, 15232, United States
University of Virginia Cancer Center
Charlottesville, Virginia, 22908, United States
MeSH Terms
Interventions
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Jyoti Malhotra
City of Hope Comprehensive Cancer Center LAO
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
September 13, 2019
First Posted
September 16, 2019
Study Start
August 4, 2020
Primary Completion (Estimated)
June 30, 2026
Study Completion (Estimated)
June 30, 2026
Last Updated
April 13, 2026
Record last verified: 2025-12
Data Sharing
- IPD Sharing
- Will share
NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.