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

Primary Purpose

Thyroid Cancer

Status

Recruiting

Phase

Phase 1

Locations

Japan

Study Type

Interventional

Intervention

Targeted alpha therapy

About this trial

This is an interventional treatment trial for Thyroid Cancer focused on measuring Targeted alpha therapy, Astatine (At-211)

Eligibility Criteria

undefined - 18 Years (Child, Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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).
Patients aged 18 years or older at the time of consent acquisition
Patients with stable general condition with PS (Performance status) of 0 to 2 in ECOG (Eastern Cooperative Oncology Group)
Patients who can be expected to survive for 6 months or more, judging from clinical symptoms and medical examination findings
Patients with no or controlled brain metastases with symptoms
Patients with no clinically significant abnormal findings in electrocardiogram, respiratory rate, and blood oxygen saturation within 30 days before registration
Patients whose laboratory values within 30days before the enrollment are within the range specified in the protocol
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:

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

Sites / Locations

Osaka University HospitalRecruiting

Arms of the Study

Arm 1

Arm Type

Other

Arm Label

Treatment group

Arm Description

Outcomes

Primary Outcome Measures

Treatment-related adverse events as assessed by CTCAE v5.0

Type, severity, frequency of occurrence and duration of adverse events

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)

Secondary Outcome Measures

Blood pressure

Systolic and diastolic blood pressure (mmHg)

Heart rate

Pulse (bpm)

Blood oxygen saturation

Percutaneous oxygen saturation (%)

Respiratory rate

Respiratory rate (times/min)

Body temperature

Body temperature (°C)

Body weight

Weight (kg)

Symptoms and examination findings

Subjective symptoms and medical examination findings

Hematological examination

White blood cell count (/μL), red blood cell count (×10^4/μL), hemoglobin (g/dL), hematocrit (%), platelet count (×10^4/μL)

Blood biochemical test

Total protein (g/dL), albumin (g/dL), total bilirubin (mg/dL), AST (U/L), ALT (U/L), ALP (U/L), γ-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)

Urinalysis

Urinary protein, urine sugar, urineous blood, urobilinogen (qualitative test)

12-lead ECG

Presence or absence of abnormal findings in waveform

Pharmacokinetic parameters 1)

AUC (Area under the plasma concentration versus time curve, Bq·min/mL)

Pharmacokinetic parameters 2)

AUC / D (Area under the plasma concentration versus time curve divided by injected dose, min/mL)

Pharmacokinetic parameters 3)

Cmax (Peak plasma concentration, Bq/mL)

Pharmacokinetic parameters 4)

Cmax / D (Peak plasma concentration divided by injected dose, /mL)

Pharmacokinetic parameters 5)

Tmax (Time to maximum plasma concentration, min)

Pharmacokinetic parameters 6)

T1 / 2 (Time from Tmax to half of maximum plasma concentration, min)

Pharmacokinetic parameters 7)

CL (Clearance, L/hr/kg)

Pharmacokinetic parameters 8)

Vss (Volume of distribution in steady state, L/kg)

Excretion 1) urinary

Urine volume (mL) and radioactivity (Bq): Radioactivity and volume will be combined to report radioactivity concentration (Bq/mL).

Excretion 2) fecal

Stool weight (g) and radioactivity (Bq): Radioactivity and weight will be combined to report radioactivity concentration (Bq/g).

Excretion 3) exhaled

Exhaled volume (mL) and radioactivity (Bq): Radioactivity and volume will be combined to report radioactivity concentration (Bq/mL).

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.

Residence time of major organs

Residence time (hr) of each organ

Absorbed dose of major organs

Absorbed dose (mGy / MBq) of each organ

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)

Preliminary effectiveness assessment 2)

Evaluation of uptake change in diagnostic [131I] NaI scans: CR , PR, SD, or PD

Preliminary effectiveness assessment 3)

Evaluation of changes in tumor markers: blood thyroglobulin (ng/mL)

Full Information

NCT ID

NCT05275946

First Posted

January 22, 2022

Last Updated

March 22, 2023

Sponsor

Osaka University

1. Study Identification

Unique Protocol Identification Number

NCT05275946

Brief Title

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

2. Study Status

Record Verification Date

March 2023

Overall Recruitment Status

Recruiting

Study Start Date

November 20, 2021 (Actual)

Primary Completion Date

March 31, 2024 (Anticipated)

Study Completion Date

September 30, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Osaka University

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Thyroid Cancer

Keywords

Targeted alpha therapy, Astatine (At-211)

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

11 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Treatment group

Arm Type

Other

Intervention Type

Drug

Intervention Name(s)

Targeted alpha therapy

Intervention Description

Single intravenous administration

Primary Outcome Measure Information:

Title

Treatment-related adverse events as assessed by CTCAE v5.0

Description

Type, severity, frequency of occurrence and duration of adverse events

Time Frame

From the start of iodine restriction to 6 months after administration

Title

Dose Limiting Toxicity

Description

Time Frame

within 4 weeks after administration

Secondary Outcome Measure Information:

Title

Blood pressure

Description

Systolic and diastolic blood pressure (mmHg)

Time Frame

within 4 weeks after administration

Title

Heart rate

Description

Pulse (bpm)

Time Frame

within 4 weeks after administration

Title

Blood oxygen saturation

Description

Percutaneous oxygen saturation (%)

Time Frame

within 4 weeks after administration

Title

Respiratory rate

Description

Respiratory rate (times/min)

Time Frame

within 4 weeks after administration

Title

Body temperature

Description

Body temperature (°C)

Time Frame

within 4 weeks after administration

Title

Body weight

Description

Weight (kg)

Time Frame

within 4 weeks after administration

Title

Symptoms and examination findings

Description

Subjective symptoms and medical examination findings

Time Frame

within 4 weeks after administration

Title

Hematological examination

Description

White blood cell count (/μL), red blood cell count (×10^4/μL), hemoglobin (g/dL), hematocrit (%), platelet count (×10^4/μL)

Time Frame

within 4 weeks after administration

Title

Blood biochemical test

Description

Time Frame

within 4 weeks after administration

Title

Urinalysis

Description

Urinary protein, urine sugar, urineous blood, urobilinogen (qualitative test)

Time Frame

within 4 weeks after administration

Title

12-lead ECG

Description

Presence or absence of abnormal findings in waveform

Time Frame

within 4 weeks after administration

Title

Pharmacokinetic parameters 1)

Description

AUC (Area under the plasma concentration versus time curve, Bq·min/mL)

Time Frame