Targeted Alpha Therapy Using Astatine (At-211) Against Differentiated Thyroid Cancer

Thyroid Cancer Clinical Trial

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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05275946
• Other study ID #: AT1-001
• Status: Recruiting
• Phase: Phase 1
• Start date: November 20, 2021
• Est. completion date: September 30, 2025

Study information

• Verified date: April 2024
• Source: Osaka University
• Contact: Tadashi Watabe, M.D., Ph.D.
• Phone: +81-6-6879-3461
• Email: watabe[@]tracer.med.osaka-u.ac.jp
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 11
• Est. completion date: September 30, 2025
• Est. primary completion date: March 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 18 Years

Eligibility

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.

Related Conditions & MeSH terms

• Thyroid Cancer
• Thyroid Diseases
• Thyroid Neoplasms

Intervention

Drug:
• Targeted alpha therapy
Single intravenous administration

Locations

Country	Name	City	State
Japan	Osaka University Hospital	Suita

Sponsors (1)

Lead Sponsor	Collaborator
Osaka University

Country where clinical trial is conducted

Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Treatment-related adverse events as assessed by CTCAE v5.0	Type, severity, frequency of occurrence and duration of adverse events	From the start of iodine restriction to 6 months after administration
Primary	Dose Limiting Toxicity	Toxicity is defined as one or more of the following items for which a causal relationship with the investigational drug cannot be ruled out.; Grade 3 * hematological toxicity that lasts for 7 days or more; Hematological toxicity of Grade 4 * or higher regardless of duration; Febrile neutropenia regardless of duration; Thrombocytopenia with bleeding tendency or requiring platelet transfusion; Anemia requiring red blood cell transfusion; Neutropenia with infection; Non-hematological toxicity of Grade 3 * or higher that does not improve with symptomatic treatment and lasts for 7 days or longer. However, the following are excluded.; Abnormal laboratory test values that are not clinically significant; Toxicity that can be controlled to Grade 2 * or less with maximum supportive care; Due to exacerbation of the underlying disease (*: Grade specified in CTCAE v.5.0J COG version)	within 4 weeks after administration
Secondary	Blood pressure	Systolic and diastolic blood pressure (mmHg)	within 4 weeks after administration
Secondary	Heart rate	Pulse (bpm)	within 4 weeks after administration
Secondary	Blood oxygen saturation	Percutaneous oxygen saturation (%)	within 4 weeks after administration
Secondary	Respiratory rate	Respiratory rate (times/min)	within 4 weeks after administration
Secondary	Body temperature	Body temperature (°C)	within 4 weeks after administration
Secondary	Body weight	Weight (kg)	within 4 weeks after administration
Secondary	Symptoms and examination findings	Subjective symptoms and medical examination findings	within 4 weeks after administration
Secondary	Hematological examination	White blood cell count (/µL), red blood cell count (×10^4/µL), hemoglobin (g/dL), hematocrit (%), platelet count (×10^4/µL)	within 4 weeks after administration
Secondary	Blood biochemical test	Total protein (g/dL), albumin (g/dL), total bilirubin (mg/dL), AST (U/L), ALT (U/L), ALP (U/L), ?-GTP (U/L), LDH (U/L), total cholesterol (mg/dL), triglyceride (mg/dL), uric acid (mg/dL), BUN (mg/dL), creatinine (mg/dL), CK (U/L), Na (mmol/L), K (mmol/L), Cl (mmol/L), Ca (mmol/L), CRP (mg/dL)	within 4 weeks after administration
Secondary	Urinalysis	Urinary protein, urine sugar, urineous blood, urobilinogen (qualitative test)	within 4 weeks after administration
Secondary	12-lead ECG	Presence or absence of abnormal findings in waveform	within 4 weeks after administration
Secondary	Pharmacokinetic parameters 1)	AUC (Area under the plasma concentration versus time curve, Bq·min/mL)	until 24 hours after administration
Secondary	Pharmacokinetic parameters 2)	AUC / D (Area under the plasma concentration versus time curve divided by injected dose, min/mL)	until 24 hours after administration
Secondary	Pharmacokinetic parameters 3)	Cmax (Peak plasma concentration, Bq/mL)	until 24 hours after administration
Secondary	Pharmacokinetic parameters 4)	Cmax / D (Peak plasma concentration divided by injected dose, /mL)	until 24 hours after administration
Secondary	Pharmacokinetic parameters 5)	Tmax (Time to maximum plasma concentration, min)	until 24 hours after administration
Secondary	Pharmacokinetic parameters 6)	T1 / 2 (Time from Tmax to half of maximum plasma concentration, min)	until 24 hours after administration
Secondary	Pharmacokinetic parameters 7)	CL (Clearance, L/hr/kg)	until 24 hours after administration
Secondary	Pharmacokinetic parameters 8)	Vss (Volume of distribution in steady state, L/kg)	until 24 hours after administration
Secondary	Excretion 1) urinary	Urine volume (mL) and radioactivity (Bq): Radioactivity and volume will be combined to report radioactivity concentration (Bq/mL).	until 24 hours after administration
Secondary	Excretion 2) fecal	Stool weight (g) and radioactivity (Bq): Radioactivity and weight will be combined to report radioactivity concentration (Bq/g).	until 24 hours after administration
Secondary	Excretion 3) exhaled	Exhaled volume (mL) and radioactivity (Bq): Radioactivity and volume will be combined to report radioactivity concentration (Bq/mL).	until 24 hours after administration
Secondary	Radioactivity concentration in major organs	Changes in radioactivity concentration (Bq/mL) in major organs over time: Whole-body imaging (planar and SPECT/CT) is performed to evaluate the distribution in the body at 1 hour, 3 hours, 24 hours after the administration.	until 24 hours after administration
Secondary	Residence time of major organs	Residence time (hr) of each organ	until 24 hours after administration
Secondary	Absorbed dose of major organs	Absorbed dose (mGy / MBq) of each organ	until 24 hours after administration
Secondary	Preliminary effectiveness assessment 1)	Evaluation of treatment effect on CT images by referring to the Revised RECIST guideline (version 1.1): CR (Complete response), PR (Partial response), SD (Stable disease), or PD (Progressive disease)	3 and 6 months after administration
Secondary	Preliminary effectiveness assessment 2)	Evaluation of uptake change in diagnostic [131I] NaI scans: CR , PR, SD, or PD	3 and 6 months after administration
Secondary	Preliminary effectiveness assessment 3)	Evaluation of changes in tumor markers: blood thyroglobulin (ng/mL)	3 and 6 months after administration