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

NCT01833520 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: 2012-0952NCI-2013-02267
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

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.

Conditions

Sarcoma

Keywords

Sarcoma; Osteosarcoma; recurrent or metastatic; Ra-223 dichloride; Radium-223 chloride; Alpharadin

Outcome Measures

Primary Outcomes (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).

  3 months

Secondary Outcomes (1)

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

  Baseline, 3 months and 6 months

Study Arms (1)

Ra-223 Dichloride

EXPERIMENTAL

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

Interventions

Ra-223 Dichloride DRUG

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.

Also known as: Alpharadin

Ra-223 Dichloride

Eligibility Criteria

• Age: 15 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• Diagnosis other than osteosarcoma.
• mTc-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.
• 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

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• Bayer: collaborator

Study Sites (1)

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Publications (1)

• 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.

  PMID: 26181034 DERIVED

Related Links

• University of Texas MD Anderson Cancer Center Website

MeSH Terms

Conditions

Sarcoma; Osteosarcoma; Recurrence; Neoplasm Metastasis

Condition Hierarchy (Ancestors)

Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Bone Tissue; Neoplasms, Connective Tissue; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neoplastic Processes

Results Point of Contact

• Title: Vivek Subbiah,Associate Professor, Invest. Cancer Therapeutics
• Organization: UT MD Anderson Cancer Center

vsubbiah@mdanderson.org

(713) 563-0393

Study Officials

• Vivek Subbiah, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 12, 2013
• First Posted: April 17, 2013
• Study Start: October 16, 2013
• Primary Completion: April 8, 2020
• Study Completion: April 8, 2020
• Last Updated: February 2, 2021
• Results First Posted: February 2, 2021

Record last verified: 2021-01

Locations

US (1)