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

Anatomic Stage IV Breast Cancer AJCC v8 Clinical Trial

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

Status Active, not recruiting

Clinical Trial 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.

Clinical Trial Description

PRIMARY OBJECTIVE: I. To determine if the combination of radium-23 dichloride (radium Ra 223 dichloride) and paclitaxel improves progression-free survival (PFS) compared to paclitaxel alone. SECONDARY OBJECTIVES: I. To determine the time to the first symptomatic skeletal event (SSE) (defined as 1st 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). II. To measure the objective response rate (ORR). III. To determine the safety of radium-223 dichloride with paclitaxel. IV. To measure overall survival (OS). EXPLORATORY OBJECTIVES: I. To perform molecular profiling assays on malignant and normal tissues, including, but not limited to, whole exome sequencing (WES) and messenger ribonucleic acid (RNA) sequencing (RNAseq), in order to: Ia. Investigate if molecular alterations in deoxyribonucleic acid (DNA) repair genes are associated with response to radium-223 dichloride, and; Ib. Investigate if loss of heterozygosity in triple negative tumors is associated with response to radium-223 dichloride. II. To contribute genetic analysis data from de-identified biospecimens to Genomic Data Commons (GDC), a well annotated cancer molecular and clinical data repository, for current and future research; specimens will be annotated with key clinical data, including presentation, diagnosis, staging, summary treatment, and if possible, outcome. III. To correlate change in level of total alkaline phosphatase, bone-specific alkaline phosphatase, and serum osteocalcin to response to radium-223 dichloride therapy. IV. To examine the radium-223 dichloride bio-distribution and absorbed dose in each bone metastatic lesions as well as elsewhere in the body including critical organs using dosimetry. V. To bank formalin-fixed, paraffin-embedded (FFPE) tissue, blood, and nucleic acids obtained from patients at the Experimental Therapeutics Clinical Trials Network (ETCTN) Biorepository at Nationwide Children's Hospital. VI. To explore the symptomatic adverse events (AE) for tolerability of each treatment arm. OUTLINE: Patients are randomized to 1 of 2 arms. ARM I: Patients receive paclitaxel intravenously (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 computed tomography (CT) scan, bone scan and/or magnetic resonance imaging (MRI), as well as collection of blood samples throughout trial. Patients may optionally undergo single photon emission computed tomography (SPECT) on trial. ARM II: Patients 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. After completion of study treatment, patients are followed up at 30 days, then every 3 months for 2 years. ;

Related Conditions & MeSH terms

• Anatomic Stage IV Breast Cancer AJCC v8
• Breast Neoplasms
• Metastatic Malignant Neoplasm in the Bone
• Neoplasms

• NCT number: NCT04090398
• Study type: Interventional
• Source: National Cancer Institute (NCI)
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: August 4, 2020
• Completion date: June 30, 2025