Efficacy of Radium 223 in Radioactive Iodine Refractory Bone Metastases From Differentiated Thyroid Cancer

NCT02390934 | Completed Phase 2

• 2 other identifiers: 2014-001070-342014/2110
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this Phase II single-arm study is to evaluate the efficacy of Radium-223 in treating bone lesions from differentiated thyroid cancer that are I-131 refractory. Based on the results of the phase III trial, the protocol using an injection of Radium-223 activity of 50 kBq/kg b.w. given 6 times at 4 weeks interval will be applied. The end point of this study will be the evaluation of Radium-223 efficacy one month after 3 administrations, i.e. at 3 months after the first injection. If disease progression at that time is excluded, patients will be treated with 3 further injections for a total of 6 administrations of Radium-223. The principal response criterion at 3 and 6 months will be the metabolic response on FDG PET/CT, but other imaging techniques will also be performed: axial skeleton MRI, 99mTc-HMDP bone scan and FNa PET/CT. Axial skeleton MRI is the reference for soft tissue study. 99mTc- HMDP bone scan is the most used and available routine tool to detect bone metastases in cancer patients, but its sensitivity in patients with bone metastases from thyroid cancer is low, because most lesions are lytic \[23\]. 18FNa PET/CT shows higher sensitivity than 99mTc-HMDP bone scan to detect bone lesions in cancer patients and is able to detect micrometastases that are not seen on bone scan \[24\] \[25\]. Preliminary results show some interest of using this tracer to evaluate the sclerotic component of bone metastases from thyroid cancer \[26\]. Furthermore preliminary data show that FNa PET/CT can be useful to quantify response to Radium-223 in prostate cancer. In only five patients evaluated by FNa PET/CT at baseline, 6 weeks and 12 weeks after 100 KBq/Kg of Radium-223, semiquantitative analysis by SUV max showed a relationship between PSA and SUV max level decrease in 3 patients (-44%, -31%, -27% vs -52%, -75, and -49% respectively) \[27\]. Finally bone metastases that are visible on morphological imaging (CT scan or on RI) are frequently submitted to local treatment modalities, and this may induce fibrosis and recalcification. Therefore, already treated metastases and not treated metastases will be studied separately as two separate subgroups of target lesions.

Conditions

Thyroid Cancer

Keywords

Radium 223; bone metastases

Outcome Measures

Primary Outcomes (1)

• Metabolic response (PERCIST criteria)

  Metabolic response according to PERCIST criteria in up to five lesions on FDG PET/CT performed 1 month after 3 monthly injections of Radium 223

  Assessed 1 months after 3 monthly injections of Radium 223

Secondary Outcomes (6)

• Pain response (numerical rating scale)

  Assessed every 30 days following the first Radium 223 up to 7 months

• Partial pain response (improvement ≥30% and <50% pain score)

  Assessed every 30 days following the first Radium 223 up to 7 months

• ECOG performance status

  Assessed every 30 days following the first Radium 223 up to 7 months

• Changes in Quality of life (QLQ-C30 and QLQ-BM22 questionnaires)

  Assessed every 30 days following the first Radium 223 up to 7 months

• Time to occurrence of first skeletal-related events

  Assessed every 30 days following the first Radium 223 up to 7 months

Study Arms (1)

Radium 223

EXPERIMENTAL

Radium-223 (Xofigo®) will be supplied in vials as a ready-to-use solution for intravenous administration. The activity (administered radioactivity) will be 50 kBq/kg b.w., and multiple treatment activities up to 6 injections will be administered at intervals of 4 weeks.

Radiation: Radium 223

Interventions

Radium 223 RADIATION

Also known as: Xofigo

Radium 223

Eligibility Criteria

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

You may qualify if:

• Affiliated to a social security regimen ;
• Patients with histologically confirmed differentiated thyroid cancer (papillary, follicular including Hurthle cell or poorly differentiated) ;
• Iodine refractory disease defined by the absence of radioiodine uptake in at least one lesion or progression of the disease within 14 months after a radioactive iodine (RAI) treatment or persistent disease after the administration of a cumulative activity of 22GBq I 131 ;
• Age ≥18 years ;
• Eastern Cooperative Oncology Group performance status 0-2 ;
• Life expectancy longer than 3 months ;
• Presence of at least one bone metastasis visible on CT scan or axial skeleton (AS) MRI and not requiring urgent locoregional treatment ;
• Presence of at least one bone metastasis with uptake on FDG PET/CT ;
• Presence of at least one bone metastasis with increased uptake on 99mTc HMDP bone scintigraphy or FNa PET/CT
• Adequate haematological (neutrophils ≥1,5×109/L; platelets ≥100×109/ L; haemoglobin \> 9g/dL), renal (creatinine \<1,5×upper limit of normal range), and hepatic (total bilirubin \< 1.5 institutional upper limit of normal), aspartate aminotransferase and alanine aminotransferase \<2,5×upper limit of normal range in the absence of liver metastases or \<5×upper limit of normal range in case of liver metastases) functions ;
• Patients receiving bisphosphonates or anti-RANK ligand (Denosumab) are allowed but patients should have received at least 2 administrations prior to Radium-223 administration and these treatments will be continued during Radium-223 treatment ;
• Blood negative pregnancy test in women of childbearing potential within 30 days prior to treatment initiation. Both men and women (of childbearing potential) who are sexually active must use adequate contraception during and for at least 6 months post-treatment ;
• Patient who is fully informed, able to comply with the protocol and who signed the informed consent.

You may not qualify if:

• Patients with another malignancy that is not in remission for at least 2 years (except for in situ cervix uterine cancer, basocellular skin cancer) ;
• Treatment with any investigational drug or with a TKI within the previous 4 weeks, or planned during the treatment period ;
• Treatment with cytotoxic chemotherapy within the previous 4 weeks, or planned during the treatment period, or failure to recover from adverse events due to cytotoxic chemotherapy administered more than 4 weeks before the study initiation ;
• Previous systemic therapy with radionuclides, including strontium-89, samarium-153, rhenium-186, rhenium-188 or radium-223 ;
• Patients with imminent or established spinal cord compression based on clinical findings and/or MRI and/or immediate need for local radiotherapy ;
• Patients with progressive visceral metastases according to RECIST 1.1 criteria assessed by CT scan and/or symptomatic brain metastases within 6 months prior to study initiation ;
• Patient already included in other clinical trial ;
• Pregnant or breast feeding women ;
• Fecal or urinary unmanageable incontinence ;
• Bone marrow dysplasia, uncontrolled diabetes or infection, NYHA Class III or IV cardiac disorders, fecal incontinence and symptomatic intestinal disease (such as Crohn disease or ulcerative colitis).

Sponsors & Collaborators

• Gustave Roussy, Cancer Campus, Grand Paris: lead

Study Sites (1)

Gustave Roussy

Villejuif, Val De Marne, 94805, France

Location

Related Publications (1)

• Deandreis D, Maillard A, Zerdoud S, Bournaud C, Vija L, Sajous C, Terroir M, Leenhardt L, Schlumberger M, Borget I, Leboulleux S. RADTHYR: an open-label, single-arm, prospective multicenter phase II trial of Radium-223 for the treatment of bone metastases from radioactive iodine refractory differentiated thyroid cancer. Eur J Nucl Med Mol Imaging. 2021 Sep;48(10):3238-3249. doi: 10.1007/s00259-021-05229-y. Epub 2021 Feb 23.

  PMID: 33619600 DERIVED

MeSH Terms

Conditions

Thyroid Neoplasms

Interventions

radium Ra 223 dichloride

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Head and Neck Neoplasms; Endocrine System Diseases; Thyroid Diseases

Study Officials

• Sophie LEBOULLEUX, MD

  Gustave Roussy, Cancer Campus, Grand Paris

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 1, 2014
• First Posted: March 18, 2015
• Study Start: October 1, 2014
• Primary Completion: April 2, 2019
• Study Completion: April 2, 2019
• Last Updated: June 11, 2019

Record last verified: 2019-06

Locations

FR (1)