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SarcomaPhase 1/2NCT01833520

Phase I Dose Escalation of Monthly Intravenous Ra-223 Dichloride in Osteosarcoma

A Phase 1/2 study testing Ra-223 Dichloride in people with Sarcoma, 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 find the highest tolerable dose of radium-223 dichloride that can be given to patients with osteosarcoma. Radium-223 chloride is designed to work like radiation therapy in cells that are actively making bone. Read more about this study

Who is it for?
Ages 15 years and older
Conditions the study is for
Sarcoma
What is being tested?
Ra-223 Dichloride
Could I receive a placebo?
No, everyone receives an active treatment
How many people
18 participants
Where
1 siteUnited States
Study dates
16 Oct 2013to 8 Apr 2020
Phase
Phase 1/2
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 15 years and older
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • Patients with progressive, locally recurrent, or metastatic osteosarcoma (i.e. high-risk only) with no standard curative options available with at least one indicator lesion avid on 99mTc-MDP scan or a Sodium Fluoride (Na F) Bone PET scan will be eligible. In addition, subjects with extremely rare bone forming osteosarcoma-like tumors that behave like osteosarcoma phenotypically and are clinically treated like osteosarcoma (eg. Malignant Fibrous Histiocytoma of Bone or malignant transformation of giant cell tumor of bone) may be included if they satisfy all of the inclusion criteria.
  • Anatomic imaging (CT or MRI) of all sites of disease along with chest CT at baseline and restaging for all patients will be done to allow for assessment of RECIST progression. RECIST progression will determine progressive disease regardless of other imaging.
  • Indicator lesion that has uptake of 99mTc-MDP on bone scan or a Sodium Fluoride ( Na F) Bone PET scan and can be subjected to quantitative assessment by this scans and possibly other means.
  • Age 15 and above and >40 kg.
  • ECOG=2 or better
  • Subjects or their guardians 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.
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  • 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).
  • Women of childbearing potential must have a negative serum or urine 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.
  • Subjects (men and women) of childbearing potential must agree to use adequate contraception beginning at the signing of the ICF until at least 30 days 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) >= 1500/mm3; Absolute Neutrophil Count (ANC) >= 1,000/mm3; Platelet (PLT) count >= 75,000/mm3; Hemoglobin (HGB) >= 8 g/dl; Total bilirubin level <= 1.5 x institutional upper limit of normal (ULN); Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) <= 2.5 x ULN; Creatinine <= 1.5 x ULN; Albumin > 25 g/L
  • Willing and able to comply with the protocol, including follow-up visits and examinations.
  • Patients with progressive, locally recurrent, or metastatic osteosarcoma (i.e. high-risk only) with at least one indicator lesion avid on 99mTc-MDP scan will be eligible.

Who cannot join

  • Diagnosis other than osteosarcoma.
  • 99mTc-MDP bone scan with no significant uptake (i.e. "nothing" for a bone-seeking isotope to target/ i.e. indicator lesion that would be expected to have the bone-seeking targeted uptake of 223-radium dichloride).
  • Other malignancy treated within the last 3 years (except non-melanoma skin cancer or low-grade superficial bladder cancer).
  • Any other serious illness or medical condition, such as but not limited to: Any active infection >= National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03 Grade 2; Cardiac failure New York Heart Association (NYHA) III or IV; Fecal incontinence (this is because of Ra-223 elimination in feces).
  • Women who are pregnant or breast-feeding.
  • Inability to comply with the protocol and/or not willing or not available for follow-up assessments.
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  • Any condition which, in the investigator's opinion, makes the subject unsuitable for trial participation.
  • Concurrent anti-cancer therapy (chemotherapy, radiation therapy, surgery, immunotherapy, biologic therapy, or tumor embolization)
  • Patients on oxygen

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

The goal of this clinical research study is to find the highest tolerable dose of radium-223 dichloride that can be given to patients with osteosarcoma.

Radium-223 chloride is designed to work like radiation therapy in cells that are actively making bone. It is designed to target new bone growth in and around bone cancer and may kill cancer cells.

Read the detailed description

Study Groups:

If you are found to be eligible to take part in this study, you will be assigned to a study group based on when you join this study. Up to 3 groups of 3 participants will be enrolled in the Phase I portion of the study, and up to 6 participants will be enrolled in Phase II.

If you are found to be eligible to take part in this study, you will be assigned to a dose level of radium-223 dichloride based on when you join this study. The first group of participants will receive the lowest dose level. Each new group will receive a higher dose than the group before it, if no intolerable side effects were seen. This will continue until the highest tolerable dose of radium-223 dichloride is found.

If you are enrolled in the Phase II portion, you will receive radium-223 dichloride at the highest dose that was tolerated in the Phase I portion.

Study Drug Administration:

You will receive radium-223 chloride by vein over several minutes on Day 1 of each 4-week cycle.

You should drink plenty of fluids before each study drug dose.

You and your caregivers will receive spoken and written instructions about safety precautions after receiving this drug.

Study Visits:

At all study visits, you will be asked about any drugs you may be taking and if you have had any side effects from them.

On Day 1 of Cycle 2-6:

  • You will have a physical exam, including measurement of your vital signs
  • You will complete a brief questionnaire about any pain that you may be experiencing. This questionnaire should take about 5-10 minutes to complete.
  • Your performance status will be recorded.
  • Blood (about 1 tablespoon) will be drawn for routine tests.
  • If you can become pregnant, you will have a urine or blood pregnancy test. If the doctor thinks it is needed, you will also have an ultrasound to check for pregnancy. To take part in this study, you cannot be pregnant.

Within 1-3 weeks after Cycle 3:

  • You will have scans such as a bone scan and CT or MRI scan to check the status of the disease.
  • Blood (about 1 tablespoon) will be drawn for routine tests.

You may have other routine tests done, including a pregnancy test, if the study doctor thinks it is needed.

Length of Study Drug Dosing:

You may continue taking the study drug 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 in this study will be over once you have completed the end-of-dosing visit (and follow-up visits if applicable).

End-of-Dosing Visit:

About 30 days after your last study drug dose:

  • You will be asked about any drugs you may be taking and if you have had any side effects from them.
  • You will have a physical exam, including measurement of your vital signs.
  • You will complete a brief questionnaire about any pain that you may be experiencing. This questionnaire should take about 5-10 minutes to complete.
  • Your performance status will be recorded.
  • Blood (about 1 tablespoon) will be drawn for routine tests.
  • You will have scans such as a bone scan and CT or MRI scan to check the status of the disease.

Follow-Up Visits:

If you are younger than 18 years old, your height and weight will be measured 1 time a year until you turn 21. These measurements may stop earlier if your height stays about the same for 2 years in a row.

Information about your health status and any side effects (especially related to your bones) will be collected and reported to the study staff every year.

This is an investigational study. Radium-223 dichloride is commercially available and FDA approved for the treatment of certain types of prostate cancer. It is currently being used for research purposes only.

Up to 20 patients will be enrolled in this study. All will be enrolled at MD Anderson.

Conditions
Sarcoma
Being tested
Ra-223 Dichloride
Keywords
Sarcoma, Osteosarcoma, recurrent or metastatic, Ra-223 dichloride, Radium-223 chloride, Alpharadin
Medical subject headings
Sarcoma, Osteosarcoma, Recurrence, Neoplasm Metastasis

What participants receive

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

  • Ra-223 DichlorideDrug

    Also called Alpharadin

    Phase I Starting Dose of Ra-223 Dichloride: 50 kBq/kg by vein over several minutes on Day 1 of each 4-week cycle.

    Phase II Starting Dose of Ra-223 Dichloride: MTD from Phase I.

Study groups in NCT01833520
Study groupRoleWhat they receive
Ra-223 DichlorideExperimentalPhase I Starting Dose of Ra-223 Dichloride: 50 kBq/kg by vein over several minutes on Day 1 of each 4-week cycle. Phase II Starting Dose of Ra-223 Dichloride: MTD from Phase I. Up to 3 groups of 3 participants will be enrolled in the Phase I portion of the study, and up to 6 participants will be enrolled in Phase II.
Receives: Drug: Ra-223 Dichloride

What is being measured

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

  1. Maximum Tolerated Dose (MTD) of Ra-223 Dichloride in Osteosarcoma

    The goal of this initial study is to determine the safety of escalating doses of monthly Ra-223 dichloride in the number of osteosarcoma participants with osteoblastic bone-forming metastases until MTD or a dose 100 kBq/kg dose is reached (whichever is first).

    Measured: 3 months

Secondary outcomes (1)

  1. Number of Participants With Objective Response of Osteosarcoma Indicator Lesions to 223-Radium Dichloride

    Alkaline phosphatase reduction to quantitative imaging techniques (99mTc-MDP, 18FDG-PET-CT, 18FNa PET-CT scans) to determine objective response of osteosarcoma indicator lesions to 223-radium dichloride. >30% increase in SUV peak indicates progression, if >30% decrease in SUV peak indicates a response and other does not meet above criteria or mixed response using the NAFCIST and PERCIST criteria.

    Measured: Baseline, 3 months and 6 months

Timeline

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

  1. First posted17 Apr 2013 (estimated)
  2. Study start16 Oct 2013
  3. Primary completion8 Apr 2020
  4. Study completion8 Apr 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 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Sequential
Masking
None (open label)
Enrolment
18 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01833520
Sponsor's protocol ID
2012-0952
Other IDs
NCI-2013-02267
Status last verified
Jan 2021
First submitted
12 Apr 2013
Last updated
2 Feb 2021
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Subbiah V, Anderson P, Rohren E. Alpha Emitter Radium 223 in High-Risk Osteosarcoma: First Clinical Evidence of Response and Blood-Brain Barrier Penetration. JAMA Oncol. 2015 May;1(2):253-5. doi: 10.1001/jamaoncol.2014.289. No abstract available.

    PubMed 26181034

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Ra-223 Dichloride in people with Sarcoma, 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 12 inclusion and 9 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 2 Feb 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 combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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 2 Feb 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?

Maximum Tolerated Dose (MTD) of Ra-223 Dichloride in Osteosarcoma (time frame: 3 months). 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 NCT01833520, 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 2 Feb 2021.

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