Clinical Trials /

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

NCT02366130

Description:

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.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

Phase II Trial of Ra-223 Dichloride and Hormonal Treatment

Title

  • Brief Title: Phase II Trial of Ra-223 Dichloride and Hormonal Treatment
  • Official Title: Phase II 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
  • Clinical Trial IDs

    NCT ID: NCT02366130

    ORG ID: 2014-0508

    NCI ID: NCI-2015-00508

    Trial Conditions

    Breast Cancer

    Trial Interventions

    Drug Synonyms Arms
    Ra-223 dichloride Xofigo, Radium-223 chloride, Radium-223 dichloride, Alpharadin Ra-223 dichloride + Denosumab
    Denosumab AMG 162, Prolia Ra-223 dichloride + Denosumab
    Hormone Therapy Ra-223 dichloride + Denosumab

    Trial Purpose

    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.

    Detailed Description

    Study Drug Administration:

    If you are found to be eligible to take part in this study, you will receive Ra-223
    dichloride by vein over about 5 minutes on Day 1 of each 28-day study cycle.

    You will also receive denosumab as an injection under the skin on Day 1 of Cycles 2-5.

    You will also receive hormone therapy while on study. Your doctor will discuss with you what
    type of hormone therapy you will have, how it will be given, and its risks.

    Study Visits:

    On Day 1 of Cycle 1, blood (about 2 teaspoons) will be drawn for routine tests.

    On Day 1 of Cycles 2-5:

    - You will have a physical exam.

    - Blood (about 2 teaspoons) will be drawn for routine tests.

    On Day 1 of Cycle 6:

    - Blood (about 2 teaspoons) and urine will be collected for routine tests.

    - Blood (about 3 tablespoons) will be drawn for biomarker testing, including genetic
    biomarkers.

    - Blood (about 5 teaspoons) will be drawn to test for CTCs, tumor markers, and genetic
    testing.

    - You will have a PET-CT scan and a bone scan to check the status of the disease. If the
    doctor thinks it is needed, you will also have an MRI.

    Length of Study Participation:

    You may continue taking the study drugs for up to 6 cycles. You will no longer be able to
    take the study drug if the disease gets worse, if intolerable side effects occur, or if you
    are unable to follow study directions.

    Your participation will be over after the end-of-study visit.

    End-of-Study Visit:

    After your last dose of study drug:

    - You will have a physical exam.

    - Blood (about 2 teaspoons) and urine will be collected for routine tests.

    - Blood (about 3 tablespoons) will be drawn for biomarker testing, including genetic
    biomarkers.

    - Blood (about 5 teaspoons) will be drawn to test for CTCs, tumor markers, and genetic
    testing.

    - You will have a PET-CT scan and either a bone scan or a CT scan to check the status of
    the disease. If the doctor thinks it is needed, you will also have an MRI.

    If the doctor thinks it is needed, you will have a bone marrow aspiration/biopsy to check
    the status of the disease.

    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.

    Trial Arms

    Name Type Description Interventions
    Ra-223 dichloride + Denosumab Experimental Ra-223 dichloride 50 kBq/kg body weight administered as a bolus intravenous (IV) injection on Day 1 of each 28 day cycle and then every four weeks thereafter for 6 cycles. Denosumab 120 mg by subcutaneous (SC) injections on Day 1 of Cycles 2-5. A single hormonal agent (ie, Tamoxifen or Aromatase Inhibitor or Fulvestrant) administered daily while on study. Physician to decide what type of hormone therapy participant will receive. Ra-223 dichloride, Denosumab, Hormone Therapy

    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 prior or one prior treatment for metastatic breast cancer; one prior treatment
    includes any one hormonal treatment or chemotherapy or one line combination treatment
    of hormonal treatment and chemotherapy. Any anti-HER2 targeting therapy in
    combination with hormonal treatment or chemotherapy will not be counted as one.

    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).

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Female

    Primary Outcome Measures

    Disease Control Rate

    Secondary Outcome Measures

    Tumor Response Rate

    Trial 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