Trial of Ra-223 Dichloride in Combination With Hormonal Therapy and Denosumab in the Treatment of Patients With Hormone-Positive Bone-Dominant Metastatic Breast Cancer
Condition: Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: Ra-223 dichloride; Denosumab; Hormone Therapy
Intervention description: 55 kBq/kg by vein on Day 1 of each 28 day cycle, and then every four weeks thereafter for 6 cycles.; 120 mg by subcutaneous (SC) injections on Day 1 of Cycles 2-5.; A single hormonal agent administered daily while on study. Physician to decide what type of hormone therapy participant will receive.
Intervention MeSH terms: Denosumab; Radium Ra 223 dichloride; Hormones
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 45.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Breast cancer; Hormone-positive bone-dominant metastatic breast cancer; Ra-223 dichloride; Xofigo; Radium-223 chloride; Radium-223 dichloride; Alpharadin; Denosumab; AMG 162; Prolia; Hormone therapy

Summary:

      The goal of this clinical research study is to learn if Xofigo® (also called Ra-223
      dichloride) combined with hormone therapy and denosumab can help to control breast cancer
      that has spread to the bones and/or bone marrow. The safety of this study drug combination
      will also be studied.

      This is an investigational study. Denosumab and the hormone therapies used in this study are
      FDA-approved and commercially available for the treatment of metastatic breast cancer. Ra-223
      dichloride is FDA-approved and commercially available for the treatment of bone metastases.
      It is considered investigational to use the combination of Ra-223 dichloride, hormone therapy
      and denosumab to treat patients with bone cancer that has spread to the bones.

      The study doctor can explain how the study drugs are designed to work.

      Up to 36 participants will be enrolled in this study. All will take part at MD Anderson.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Stage IV breast cancer with metastases to the bone and/or bone marrow.

          2. Pathological or radiographically confirmation of metastases to the bone and/or bone
             marrow. (The definition of radiologic diagnosis of bone metastasis is based on typical
             and highly reliable imaging findings in studies such as bone scan (new or multiple
             TC99m positive lesions), PET/CT (new or multiple FRG positive lesions), and MRI
             (typical T1w replacement, T2w positive and T1 plus contrast media positive) for bone
             metastasis with 2 or more lesions. If the bone metastasis is highly suspected or not
             well defined by imaging, bone biopsy is necessary for confirmation.)

          3. Visible uptake in at least one lesion on bone scanning prior to radium therapy.

          4. No limit in number of prior hormonal agents in metastatic breast cancer; only one
             prior chemotherapy is allowed in metastatic setting. Anti-HER2 targeting therapy,
             CDK4/6 inhibitor, other targeted therapy (e.g., mTOR or PI3K inhibitor) in combination
             with hormonal treatment will be counted as one hormonal agent. Any anti-HER2 targeting
             therapy in combination with chemotherapy will not be counted as one additional
             treatment.

          5. Breast tumors with hormone receptor positive disease (ER+/PR+, ER+/PR- regardless of
             HER2 status).

          6. ECOG performance score of 0, 1.

          7. Age =/> 18 years.

          8. All acute toxic effects of any prior treatment have resolved to NCI-CTCAE v4.0 Grade 1
             or less at the time of signing the Informed Consent Form (ICF).

          9. Subjects (men and women) of childbearing potential must agree to use adequate
             contraception beginning at the signing of the ICF until at least 6 months after the
             last dose of study drug. The definition of adequate contraception will be based on the
             judgment of the principal investigator or a designated associate.

         10. Acceptable hematology and serum biochemistry screening values: White Blood Cell Count
             (WBC) =/> 3,000/mm3 Absolute Neutrophil Count (ANC) =/> 1,500/mm3 Platelet (PLT) count
             =/> 100,000/mm3 Hemoglobin (HGB) =/> 10 g/dl Total bilirubin level </=2.0 x
             institutional upper limit of normal (ULN) Aspartate aminotransferase (AST) and alanine
             aminotransferase (ALT) </= 3.0 x ULN Creatinine </= 1.5 x ULN

         11. Subjects must be able to understand and be willing to sign the written informed
             consent form. A signed informed consent form must be appropriately obtained prior to
             the conduct of any trial-specific procedure.

        Exclusion Criteria:

          1. Following breast cancer disease conditions are not eligible: A) Single Bone Lesion.
             B)Two or more visceral metastasis C) Single visceral lesion < 2cm without any
             laboratory changes or clinical symptoms due to the metastatic lesion is permitted.
             D)Presence of brain metastases E) Imminent spinal cord compression based on clinical
             findings and/or magnetic resonance imaging (MRI). T F) Impending fracture, spinal cord
             compression, and/or potentially unstable compression fracture of vertebral body with
             possibility of cord compression. G) Life expectancy severely limited by concomitant
             illness (less than 12 months). H) Concurrent external beam radiation therapy to non
             target lesion is permitted.

          2. Following prior treatments are not eligible. A) Use of any investigational agent
             within 30 days preceding enrollment. B) Treatment with cytotoxic chemotherapy within
             previous 4 weeks C) Failure to achieve </= Grade 2 AE resolution from cytotoxic
             chemotherapy administered more than 4 weeks previous (however, ongoing neuropathy is
             permitted). D) Received systemic therapy with radionuclides (e.g., strontium-89,
             samarium-153, rhenium-186, or rhenium-188, or Ra-223 dichloride) for the treatment of
             bony metastases.

          3. Following medical conditions are not eligible. A) Other malignancy treated within the
             last 3 years (except non melanoma skin cancer or low-grade superficial bladder cancer
             or cervical dysplasia) B) Any other serious illness or medical condition, such as but
             not limited to: Any infection =/> National Cancer Institute Common Terminology
             Criteria for Adverse Events (NCI-CTCAE) version 4.03 Grade 2. C) Cardiac failure New
             York Heart Association (NYHA) III or IV. D) Crohn's disease or ulcerative colitis-Bone
             marrow dysplasia or Myelodysplastic syndrome.

          4. Women who are pregnant or breast-feeding. Women of childbearing potential must have a
             negative serum pregnancy test performed within 7 days prior to the start of study
             drug. Post-menopausal women (defined as no menses for at least 1 year) and surgically
             sterilized women are not required to undergo a pregnancy test.

          5. Any condition which, in the investigator's opinion, makes the subject unsuitable for
             trial participation.

          6. Major surgery within 30 days prior to start of study drug.

          7. Excluded therapies and medications, previous and concomitant: A) Concurrent
             anti-cancer therapy (chemotherapy, surgery, immunotherapy, biologic therapy, anti-HER
             2 targeting therapies, or tumor embolization) other than Ra 223 dichloride. Concurrent
             external beam radiation therapy is permitted.B) Prior use of Ra-223 dichloride. C)
             Concurrent use of another investigational drug or device therapy (i.e., outside of
             study treatment) during, or within 4 weeks of trial entry (signing of the informed
             consent form).