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Breast CancerPhase 2NCT02366130

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

A Phase 2 study testing Ra-223 dichloride, Denosumab and Hormone Therapy in people with Breast Cancer, run by M.D. Anderson Cancer Center at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older, women only
Conditions the study is for
Breast Cancer
What is being tested?
Ra-223 dichloride, Denosumab and Hormone Therapy
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
45 participants
Where
1 siteUnited States
Study dates
11 Feb 2015to 16 Dec 2020
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Stage IV breast cancer with metastases to the bone and/or bone marrow.
  • 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.)
  • Visible uptake in at least one lesion on bone scanning prior to radium therapy.
  • 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.
  • Breast tumors with hormone receptor positive disease (ER+/PR+, ER+/PR- regardless of HER2 status).
  • ECOG performance score of 0, 1.
Show all 11Show fewer
  • Age =/> 18 years.
  • 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).
  • 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.
  • 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
  • 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.

Who cannot join

  • 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.
  • 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.
  • 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.
  • 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.
  • Any condition which, in the investigator's opinion, makes the subject unsuitable for trial participation.
  • Major surgery within 30 days prior to start of study drug.
  • 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).

Trial locations and contacts

1 site in 1 country.

United States1 site

  • University of Texas MD Anderson Cancer Center

    Houston, Texas, 77030

Other trials in United States

About this study

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

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.

Read more

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.

Read the 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 no more than 1 minute 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 1- 6.

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.
Conditions
Breast Cancer
Being tested
Ra-223 dichloride, Denosumab, Hormone Therapy
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
Medical subject headings
Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Ra-223 dichlorideDrug

    Also called Xofigo, Radium-223 chloride, Radium-223 dichloride, Alpharadin

    55 kBq/kg by vein on Day 1 of each 28 day cycle, and then every four weeks thereafter for 6 cycles.

  • DenosumabDrug

    Also called AMG 162, Prolia

    120 mg by subcutaneous (SC) injections on Day 1 of Cycles 2-5.

  • Hormone TherapyDrug

    A single hormonal agent administered daily while on study. Physician to decide what type of hormone therapy participant will receive.

Study groups in NCT02366130
Study groupRoleWhat they receive
Ra-223 dichloride + DenosumabExperimentalRa-223 dichloride 55 kBq/kg administered as a bolus intravenous (IV) injection (over 1 minute) through a secure in-dwelling catheter on day 1 of the study 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.
Receives: Drug: Ra-223 dichloride; Drug: Denosumab; Drug: Hormone Therapy

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Participants With Disease Control Rate at 9 Months

    Disease control rate is defined as the rate of the patients at that time with clinically complete or partial response or stable disease.

    Measured: 9 months from receiving the first dose of Radium-223

  2. The Number of Participants With Disease Control Rate at 6 Months

    Disease control rate is defined as the rate of the patients at that time with clinically complete or partial response or stable disease.

    Measured: 6 months from receiving the first dose of Radium-223

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted19 Feb 2015 (estimated)
  2. Study start11 Feb 2015
  3. Primary completion16 Dec 2020
  4. Study completion16 Dec 2020

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
45 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02366130
Sponsor's protocol ID
2014-0508
Other IDs
NCI-2015-00508
Status last verified
Oct 2021
First submitted
11 Feb 2015
Last updated
7 Oct 2021
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Ueno NT, Tahara RK, Fujii T, Reuben JM, Gao H, Saigal B, Lucci A, Iwase T, Ibrahim NK, Damodaran S, Shen Y, Liu DD, Hortobagyi GN, Tripathy D, Lim B, Chasen BA. Phase II study of Radium-223 dichloride combined with hormonal therapy for hormone receptor-positive, bone-dominant metastatic breast cancer. Cancer Med. 2020 Feb;9(3):1025-1032. doi: 10.1002/cam4.2780. Epub 2019 Dec 18.

    PubMed 31849202

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Ra-223 dichloride, Denosumab and Hormone Therapy in people with Breast Cancer, run by M.D. Anderson Cancer Center at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 7 Oct 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 7 Oct 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants With Disease Control Rate at 9 Months (time frame: 9 months from receiving the first dose of Radium-223). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02366130, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Oct 2021.

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