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

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ClinicalTrials.gov Identifier: NCT01833520
Recruitment Status : Active, not recruiting
First Posted : April 17, 2013
Last Update Posted : May 29, 2019
Sponsor:
Collaborator:
Bayer
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Brief 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. It is designed to target new bone growth in and around bone cancer and may kill cancer cells.


Condition or disease Intervention/treatment Phase
Sarcoma Drug: Ra-223 Dichloride Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 15 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I Dose Escalation of Monthly Intravenous Ra-223 Dichloride in Osteosarcoma
Study Start Date : October 2013
Estimated Primary Completion Date : October 2019
Estimated Study Completion Date : October 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Ra-223 Dichloride

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.

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.

Drug: Ra-223 Dichloride

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.

Other Name: Alpharadin




Primary Outcome Measures :
  1. Maximum Tolerated Dose (MTD) of Ra-223 Dichloride in Osteosarcoma [ Time Frame: 3 months ]
    If at least 2 patients are observed to have a dose-limiting toxicity (DLT), the MTD will have been exceeded and no further patients will be enrolled at this dose level or at any higher dose level. The prior dose level is defined as the MTD (unless only 3 patients have been treated at that level, in which case it is the tentative MTD). A tentative MTD becomes final when a total of 6 patients are treated with less than 2 showing DLT. Dose-limiting toxicities include all adverse experiences that are related to study medication, and clearly not related to disease progression or intercurrent illness.


Secondary Outcome Measures :
  1. Objective Response of Osteosarcoma Indicator Lesions to 223-Radium Dichloride [ Time Frame: Baseline, 3 months and 6 months ]
    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.



Information from the National Library of Medicine

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Ages Eligible for Study:   15 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. 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.
  2. 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.
  3. 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.
  4. Age 15 and above and >40 kg.
  5. ECOG=2 or better
  6. 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.
  7. 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).
  8. 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.
  9. 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.
  10. 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
  11. Willing and able to comply with the protocol, including follow-up visits and examinations.
  12. 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.

Exclusion Criteria:

  1. Diagnosis other than osteosarcoma.
  2. 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).
  3. Other malignancy treated within the last 3 years (except non-melanoma skin cancer or low-grade superficial bladder cancer).
  4. 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).
  5. Women who are pregnant or breast-feeding.
  6. Inability to comply with the protocol and/or not willing or not available for follow-up assessments.
  7. Any condition which, in the investigator's opinion, makes the subject unsuitable for trial participation.
  8. Concurrent anti-cancer therapy (chemotherapy, radiation therapy, surgery, immunotherapy, biologic therapy, or tumor embolization)
  9. Patients on oxygen

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01833520


Locations
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United States, Texas
University of Texas MD Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
Bayer
Investigators
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Principal Investigator: Vivek Subbiah, MD M.D. Anderson Cancer Center

Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT01833520     History of Changes
Other Study ID Numbers: 2012-0952
NCI-2013-02267 ( Registry Identifier: NCI CTRP )
First Posted: April 17, 2013    Key Record Dates
Last Update Posted: May 29, 2019
Last Verified: May 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by M.D. Anderson Cancer Center:
Sarcoma
Osteosarcoma
recurrent or metastatic
Ra-223 dichloride
Radium-223 chloride
Alpharadin

Additional relevant MeSH terms:
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Sarcoma
Osteosarcoma
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Bone Tissue
Neoplasms, Connective Tissue