Phase II Trial of Radium-223 Dichloride in Combination With Paclitaxel in Patients With Bone Metastatic Breast Cancer

Plain English Summary

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 is a Phase 2 clinical trial sponsored by National Cancer Institute (NCI) studying Anatomic Stage IV Breast Cancer AJCC v8, Metastatic HER2-Negative Breast Carcinoma, Metastatic Malignant Neoplasm in the Bone. This trial tests if adding a radioactive drug (radium-223 dichloride) to standard chemotherapy (paclitaxel) is more effective for advanced breast cancer that has spread to the bones. It is for men and women with advanced breast cancer that has spread to at least two areas in the bone, and who meet specific health and cancer criteria. Participation involves receiving either the combination treatment or paclitaxel alone, with regular medical check-ups, scans, and blood tests. Standard chemotherapy (paclitaxel) is the current alternative treatment for this condition. The trial aims to enroll 70 participants.

Official 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.

Who Can Participate

Here is what you need to know about eligibility for this trial. You can join if you are 18 or older, have advanced breast cancer that has spread to the bones, and your cancer is HER2-negative. You cannot join if you have more than five non-bone tumors, or if your brain metastases are not stable or treated. You must have good general health, with specific blood count and organ function levels, and be able to receive paclitaxel treatment. Women of childbearing potential must agree to use effective contraception during and after the study. This trial is studying Anatomic Stage IV Breast Cancer AJCC v8, Metastatic HER2-Negative Breast Carcinoma, Metastatic Malignant Neoplasm in the Bone, so participants generally need a confirmed diagnosis.

What They're Measuring

The main goal is to see how long patients live without their cancer getting worse (progression-free survival), meaning the treatment is controlling the cancer. The specific primary outcome measures are: Progression-free survival (PFS) (From randomization to the first documented tumor progression or death due to any cause, whichever occurred first, assessed up to 2 years). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This trial is in Phase 2, which tests whether the treatment actually works against the target condition. Phase 2 trials involve 100-300 patients and continue to monitor safety while evaluating effectiveness. This phase often tests different dosages to find the optimal amount. About 33% of Phase 2 drugs advance to Phase 3. If successful, the treatment will move to large-scale Phase 3 trials needed for FDA approval.

Why This Trial Matters

This trial aims to improve treatment for breast cancer that has spread to the bones, a common and painful complication, by exploring a new combination therapy. Phase 2 success would typically lead to larger Phase 3 trials needed for regulatory approval. This research targets Anatomic Stage IV Breast Cancer AJCC v8, Metastatic HER2-Negative Breast Carcinoma, Metastatic Malignant Neoplasm in the Bone, where improved treatment options are needed.

Investor Insight

This trial explores a targeted radiation therapy for bone metastases, a significant area of unmet need in breast cancer treatment, potentially offering a new option in a competitive landscape. Phase 2 trials have approximately a 15-20% chance of eventually gaining FDA approval.

Is This Trial Right for Me?

Ask your doctor about the potential benefits and risks of both radium therapy and paclitaxel, and how this combination might affect your specific situation. Participation involves regular clinic visits for treatment, blood draws, scans (like CT or MRI), and bone scans to monitor your cancer and overall health. You will need to continue taking any prescribed bone-strengthening medications like bisphosphonates or denosumab. The trial is being conducted at 20 sites. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: RANDOMIZED
• Model: PARALLEL
• Masking: NONE
• Enrollment: 70 participants

Interventions

• PROCEDURE: Biospecimen Collection — Correlative studies
• PROCEDURE: Bone Scan — Undergo bone scan
• PROCEDURE: Computed Tomography — Undergo CT scan
• OTHER: Electronic Health Record Review — Ancillary studies
• PROCEDURE: Magnetic Resonance Imaging — Undergo MRI

Primary Outcomes

• Progression-free survival (PFS) (From randomization to the first documented tumor progression or death due to any cause, whichever occurred first, assessed up to 2 years)

Secondary Outcomes

• 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)

Full Eligibility Criteria

Inclusion Criteria:

* 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
* Hemoglobin \> 10 g/dL
* Human immunodeficiency virus (HIV)-infected patients on effective antiretroviral therapy with undetectable viral load within 6 months are eligible for this trial
* For patients with evidence of chronic hepatitis B virus (HBV) infection, HBV viral load must be undetectable on suppressive therapy if indicated
* Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
* Patients with asymptomatic, treated brain metastases are permitted if there is no evidence of progression for at least 4 weeks after central nervous system (CNS)-directed treatment, as ascertained by clinical examination or brain imaging (magnetic resonance imaging \[MRI\] or CT scan) during the screening period
* Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial. History of other active malignancy requiring treatment within the last 3 years or bone marrow dysplasia such as myelodysplastic syndrome (MDS) is not allowed
* Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association functional classification. To be eligible for this study, patients should be class 2B or better
* Concomitant use of bisphosphonates or denosumab is required (except if medical contraindication such as hypocalcemia or concern for osteonecrosis of the jaw). If not already on bone modifying agents, patient must initiate such therapy within one month before start of study treatment
* The effects of radium-223 dichloride on the developing human fetus are unknown. For this reason and because alpha particle-emitting radiopharmaceutical agents as well as other therapeutic agents used in this trial are known to be teratogenic, women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for at least 6 months after the last dose. Should a woman become pregnant or sus

Trial Locations

• University of Alabama at Birmingham Cancer Center, Birmingham, Alabama, United States
• City of Hope Comprehensive Cancer Center, Duarte, California, United States
• UC Irvine Health/Chao Family Comprehensive Cancer Center, Orange, California, United States
• University of California Davis Comprehensive Cancer Center, Sacramento, California, United States
• UM Sylvester Comprehensive Cancer Center at Coral Gables, Coral Gables, Florida, United States
• UM Sylvester Comprehensive Cancer Center at Deerfield Beach, Deerfield Beach, Florida, United States
• University of Miami Miller School of Medicine-Sylvester Cancer Center, Miami, Florida, United States
• UM Sylvester Comprehensive Cancer Center at Kendall, Miami, Florida, United States
• UM Sylvester Comprehensive Cancer Center at Plantation, Plantation, Florida, United States
• University of Chicago Comprehensive Cancer Center, Chicago, Illinois, United States
• ...and 10 more locations

Frequently Asked Questions

Related Conditions

• Breast Cancer
• Metastatic Breast Cancer
• Bone Metastases
• Stage IV Breast Cancer
• HER2-Negative Breast Cancer
• Triple-Negative Breast Cancer
• Hormone Receptor-Positive Breast Cancer
• Bone Pain
• Cancer Treatment
• Oncology

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