Phase I investigator-initiated clinical trial against differentiated thyroid cancer using TAH-1005

JRCT ID: jRCT2051210144

Registered date:28/12/2021

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Differentiated thyroid cancer (papillary cancer, follicular cancer)
• Date of first enrollment: 28/12/2021
• Target sample size: 32
• Study type: Interventional
• Intervention(s): A single intravenous injection of TAH-1005 (1.25, 2.5, 3.5, 5, 7, or 10 MBq/kg).

Outcome(s)

Primary Outcome

1) Adverse events
Measurement items: Presence / absence, type, severity, frequency of occurrence and duration of adverse events
Measurement time: From the start of iodine restriction to 6 months after administration, or at the time of discontinuation
Evaluation Criteria: Japanese translation of CTCAE (Common Terminology Criteria for Adverse Events) 5.0th Edition

2) Dose limiting toxicity (DLT)
Toxicity is defined as toxicity when one or more of the following items for which a causal relationship with the investigational drug cannot be ruled out within 4 weeks after administration of the investigational drug.
a) Grade 3 hematological toxicity that lasts for 7 days or more
b) Hematological toxicity of Grade 4 or higher regardless of duration
c) Febrile neutropenia regardless of duration
d) Thrombocytopenia with bleeding tendency or requiring platelet transfusion
e) Anemia requiring red blood cell transfusion
f) Neutropenia with infection
g) 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 which 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

Secondary Outcome

1) Secondary evaluation items related to safety
The following items are used as secondary evaluation items related to safety.
(1) Vital signs, etc. (blood pressure, pulse, blood oxygen saturation), respiratory rate, body temperature
(2) Weight
(3) Awareness / objective findings
(4) Hematological examination
(5) Blood biochemical test
(6) Urinalysis
(7) 12-lead ECG

2) Evaluation of pharmacokinetic parameters
For the evaluation of pharmacokinetics, the radiation dose of the collected blood sample is measured, and the pharmacokinetic parameters are calculated based on the measured radiation dose.
(1) Blood collection points: At the time of administration (collected immediately before administration), 30 seconds (+/- 10 seconds), 1 minute (+/- 20 seconds), 2 minutes (+/- 30 seconds), 10 minutes (+/- 1 minute), 1 hour after administration (+/- 10 minutes), 3 hours (+/- 15 minutes), 6 hours (+/- 30 minutes), 24 hours (+/- 2 hours)
(2) Handling of blood samples
As a blood sample for drug concentration measurement, about 2 mL of blood is collected at a predetermined time with a heparin-containing syringe.
(3) Radiation dose measurement method
500 mic.L is separated from the heparin-treated blood sample, and the weight and radiation dose are measured with a radiation measuring device. The remaining specimens are centrifuged to measure plasma weight and radiation dose.
(4) Pharmacokinetic parameters to be calculated: AUC, AUC / D, Cmax, Cmax / D, Tmax, T1 / 2, CL (clearance), Vss (volume of distribution in steady state)

3) Excretion (urinary, fecal, exhaled)
Collect urine, stool, and exhaled breath in order to understand the excretory dynamics.
(1) Measurement items: urine volume (mL) and radiation dose, stool weight and radiation dose, exhaled volume and radiation dose
(2) Measurement time:
Urine (1 hour, 1-3 hours, 3-6 hours, 6-24 hours after administration)
Stool (every time of defecation up to 24 hours after administration)
Exhalation (5 minutes (+/- 1 minute), 30 minutes (+/- 5 minutes), 3 hours (+/- 15 minutes) after administration)

4) Whole body scan using gamma camera (SPECT / CT) and evaluation of absorbed dose
Whole-body imaging is performed to evaluate the distribution in the body, and local SPECT / CT imaging is added as needed. Calculate the change in radioactivity concentration and residence time of each organ, and calculate the absorbed dose (mGy / MBq).
(1) Measurement time: 1 hour, 3 hours, 24 hours after administration
(2) Evaluation items: Changes in radioactivity concentration in major organs in the body over time, absorbed dose of each organ (mGy / MBq)

5) Preliminary effectiveness assessment
(1) Judgment of tumor shrinkage effect on images (when target lesion is present by RECIST in screening CT)
To determine the tumor shrinkage effect, refer to "Guidelines for determining the therapeutic effect of solid tumors (RECIST guidelines) revised version 1.1-Japanese translation JCOG version-: Revised RECIST guideline (version 1.1)" for metastasis / recurrence on CT. Evaluate the lesion.
(2) [131^I] Changes in NaI uptake capacity
Diagnostic [131^I] NaI scans were performed at 3 and 6 months after screening and administration to estimate the expression level of NIS (sodium iodide cotransporter), which is a mechanism for taking up iodine / astatine, from changes in the degree of accumulation. , Evaluate the residual degree of thyroid cancer cells.
(3) Evaluation of changes in tumor markers over time
To evaluate changes over time in blood thyroglobulin, which is a tumor marker for differentiated thyroid cancer.

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Both

Include 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.

Exclude 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 Information

• Primary Sponsor: Watabe Tadashi
• Source(s) of Monetary Support: Japan Agency for Medical Research and Development,Alpha Fusion Incorporated