Clinical trial NCT05275946: Targeted Alpha Therapy Using Astatine (At-211) Against Differentiated Thyroid Cancer
Official title: Phase I Investigator-initiated Clinical Trial in Patients With Differentiated Thyroid Cancer (Papillary Cancer, Follicular Cancer) by the Targeted Alpha Therapy Drug TAH-1005 ([211At] NaAt) (Alpha-T1 Study)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Thyroid Cancer
Keywords: Targeted alpha therapy
Astatine (At-211)
Lead sponsor: Osaka University
Sponsor class: OTHER
First posted: 2022-03-11
Enrollment: 11
Sex: ALL
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Single intravenous administration of TAH-1005 is performed in patients with differentiated thyroid cancer (papillary cancer, follicular cancer) who cannot obtain therapeutic effect with standard treatment or who have difficulty in implementing and continuing standard treatment. The safety, pharmacokinetics, absorbed dose, and efficacy will be evaluated to determine the recommended dose for Phase II clinical trial.

Detailed description: Radioactive iodine (I-131) has long been used clinically for patients with metastatic differentiated thyroid cancer. However, some patients are refractory to repetitive I-131 treatment, despite the targeted regions showing sufficient iodine uptake. In such patients, beta-particle therapy using I-131 is inadequate and another strategy is needed using more effective radionuclide targeting the sodium/iodide symporter (NIS). Astatine (At-211) is receiving increasing attention as an alpha-emitter for targeted radionuclide therapy. At-211 is a halogen element with similar chemical properties to iodine. Alpha particles emitted from At-211 has higher linear energy transfer as compared to beta particles from I-131 and exert a better therapeutic effect by inducing DNA double strand breaks and free radical formation. Thus, targeted alpha therapy using At-211 is highly promising for the treatment of advanced differentiated thyroid cancer.

Eligibility criteria: Inclusion Criteria:

1. Patients with differentiated thyroid cancer (papillary cancer, follicular cancer) after total thyroidectomy who meet the following conditions (1) resistance to standard treatment or (2) difficulty in continuing standard treatment (1) Patients who are refractory to standard treatment such as 131I-NaI treatment Insufficient therapeutic effect after 3 or more 131I-NaI treatments. 131I-NaI treatment resistance and difficulty in performing or continuing tyrosine kinase inhibitor (TKI) treatment (2) Patients who have difficulty continuing standard treatment such as 131I-NaI treatment Ablation for residual thyroid or 131I-NaI treatment for relapsed / metastatic lesions has been performed, but relapsed / metastatic lesions were observed at the time of participation in this study, and 131I-NaI is the standard treatment. If it is difficult to continue treatment or if local radiation therapy (including addition) is not indicated (if it is not 131I-NaI treatment resistant, TKI treatment is not indicated).
2. Patients aged 18 years or older at the time of consent acquisition
3. Patients with stable general condition with PS (Performance status) of 0 to 2 in ECOG (Eastern Cooperative Oncology Group)
4. Patients who can be expected to survive for 6 months or more, judging from clinical symptoms and medical examination findings
5. Patients with no or controlled brain metastases with symptoms
6. Patients with no clinically significant abnormal findings in electrocardiogram, respiratory rate, and blood oxygen saturation within 30 days before registration
7. Patients whose laboratory values within 30days before the enrollment are within the range specified in the protocol
8. Patients who thoroughly listened to the explanation of the clinical trial, agreed to the examination, visit during the observation period and follow-up survey, contraception during the clinical trial period, etc. according to the clinical trial protocol, and signed the consent document.

Exclusion Criteria:

1. Patients who need fertility preservation
2. Pregnant or potentially pregnant women, lactating patients
3. Patients with active double cancer (simultaneous double cancer and ectopic double cancer with a disease-free period of 5 years or less)
4. Patients who received other investigational or unapproved drugs within 5 weeks prior to enrollment
5. Patients who received chemotherapy, immunotherapy or radiation therapy within 8 weeks prior to enrollment in this study
6. Patients with uncontrollable active infections
7. HBsAg positive, HCV antibody positive or HIV antibody positive patients
8. Patients with mental illness or psychiatric symptoms who are judged to be difficult to participate in clinical trials
9. Other patients who are judged to be inappropriate by the investigator, etc.

Primary outcomes:
measure: Treatment-related adverse events as assessed by CTCAE v5.0
timeFrame: From the start of iodine restriction to 6 months after administration
measure: Dose Limiting Toxicity
timeFrame: within 4 weeks after administration
Secondary outcomes:
measure: Blood pressure
timeFrame: within 4 weeks after administration
measure: Heart rate
timeFrame: within 4 weeks after administration
measure: Blood oxygen saturation
timeFrame: within 4 weeks after administration
measure: Respiratory rate
timeFrame: within 4 weeks after administration
measure: Body temperature
timeFrame: within 4 weeks after administration
measure: Body weight
timeFrame: within 4 weeks after administration
measure: Symptoms and examination findings
timeFrame: within 4 weeks after administration
measure: Hematological examination
timeFrame: within 4 weeks after administration
measure: Blood biochemical test
timeFrame: within 4 weeks after administration
measure: Urinalysis
timeFrame: within 4 weeks after administration
measure: 12-lead ECG
timeFrame: within 4 weeks after administration
measure: Pharmacokinetic parameters 1)
timeFrame: until 24 hours after administration
measure: Pharmacokinetic parameters 2)
timeFrame: until 24 hours after administration
measure: Pharmacokinetic parameters 3)
timeFrame: until 24 hours after administration
measure: Pharmacokinetic parameters 4)
timeFrame: until 24 hours after administration
measure: Pharmacokinetic parameters 5)
timeFrame: until 24 hours after administration
measure: Pharmacokinetic parameters 6)
timeFrame: until 24 hours after administration
measure: Pharmacokinetic parameters 7)
timeFrame: until 24 hours after administration
measure: Pharmacokinetic parameters 8)
timeFrame: until 24 hours after administration
measure: Excretion 1) urinary
timeFrame: until 24 hours after administration
measure: Excretion 2) fecal
timeFrame: until 24 hours after administration
measure: Excretion 3) exhaled
timeFrame: until 24 hours after administration
measure: Radioactivity concentration in major organs
timeFrame: until 24 hours after administration
measure: Residence time of major organs
timeFrame: until 24 hours after administration
measure: Absorbed dose of major organs
timeFrame: until 24 hours after administration
measure: Preliminary effectiveness assessment 1)
timeFrame: 3 and 6 months after administration
measure: Preliminary effectiveness assessment 2)
timeFrame: 3 and 6 months after administration
measure: Preliminary effectiveness assessment 3)
timeFrame: 3 and 6 months after administration
Other outcomes:
Locations:
city: Suita
country: Japan
facility: Osaka University Hospital
Study officials:
References: