Neoplasms

All Conditions

Gland and Hormone Related Diseases

Carcinoma

Thyroid Neoplasms

Thyroid Diseases

Thyroid Cancer, Papillary

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Endocrine System Diseases

Endocrine Gland Neoplasms

Head and Neck Neoplasms

Adenocarcinoma

Adenocarcinoma, Papillary

Anti-Arrhythmia Agents

Cardiotonic Agents

All Drugs and Chemicals

Micronutrients

Anti-Infective Agents

Digoxin

Iodine

Cadexomer iodine

Enzyme Inhibitors

Protective Agents

This arm will consist of 10 patients with radioiodine refractory non-medullary thyroid carcinoma. All participants will be treated according to the same protocol.

Participants will be treated with digoxin tablets for 3 weeks. On the first they, participants will start with a starting dosage of 3x0.25mg with 6 hours between each administration. Thereafter they will continue with a dosage of 1x0.25mg. Participants aged \>70 years or with body weight \<55kg will initiate a starting dosage of 3x0.125mg with 6 hours between each administration. Thereafter they will continue with a dosage of 1x0.125mg.

After one week the blood concentration of digoxin will be measured. According to this blood concentration, the dose of digoxin will be adjusted.

Digoxin tablet

Non-medullary thyroid carcinoma has a good prognosis in most patients. However, a small subset of patients nevertheless develop metastatic or locally advanced and unresectable disease which in some cases also becomes radioiodine refractory. In these patients treatment options are very limited. Earlier cell line and animal studies have shown that digoxin can reinduce radioiodine uptake in non-medullary thyroid cancer. This study serves as a proof of principle study to assess the possibility of digoxin to reinduce radioiodine uptake in adult humans with metastatic or locally advanced non-medullary radioiodine refractory thyroid carcinoma.

10 participants with radioiodine refractory metastatic or locally advanced non-medullary thyroid carcinoma will enroll in this study. All participants will be treated according to the same protocol.

Digoxin for the Reinduction of Radioiodine Uptake in Metastatic or Locally Advanced Non-medullary Thyroid Carcinoma

At baseline and after 3 weeks of digoxin treatment, a scintigraphy scan will be conducted. Reinduction of radioiodine uptake is defined as enough uptake that a treatment with high-dose radioactive iodine is possible.

Participants with reinduction of radioiodine uptake in the target lesion will be offered a treatment with high-dose radioactive iodine, according to the guidelines for the treatment of thyroid carcinoma. The beneficial effects of this treatment will be measured after 6 months with a computertomography scan and will be described using the RECIST criteria.

All serious adverse events (SAE) occuring during the digoxin treatment will be described.

Radboud University Medical Center

Antineoplastic Agents

Apatinib

Protein Kinase Inhibitors

In phase A, subjects receiving a single 0.25 mg of digoxin orally and wash-out for 5 days, then apatinib once daily will be conducted on D5 through D16 ； In addition, a single dose of 0.25 mg digoxin (in combination with apatinib) will be orally administered in fasting conditions on D12；

Apatinib at a dosage of will be administered daily from on D5 through D16

Apatinib Mesylate

Digoxin at a dosage of 0.25mg will be administered at day 1 and day 12

Apatinib, an oral inhibitor of vascular endothelial growth factor receptor 2#VEGFR-2#, Induces Transporter Pgp function in vitro. This study in patients with advanced cancer evaluated the effect of Apatinib on Transporter Pgp function by comparing the pharmacokinetics of Transporter Pgp-specific probe drugs in the presence and absence of Apatinib. The probes used Substrate Digoxin.

A Pharmacokinetic Interaction Study Between Apatinib Mesylate and Transporter Pgp Substrate Digoxin in Advanced Solid Tumor Subjects

A Single Arm, Open and Fixed Sequence Study to Investigate the Pharmacokinetic Effects of Apatinib Mesylate on Transporter Pgp Substrate Digoxin in Advanced Solid Tumor Subjects

Peak Plasma Concentration (Cmax) of digoxin

Area under the plasma concentration versus time curve (AUC) of digoxin

Time of maximum observed concentration (Tmax) of digoxin

Total body clearance for extravascular administration (CL/F) of digoxin

An adverse event is any untoward medical occurrence in a patient or clinical study participant criteria

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Digoxin for the Reinduction of Radioiodine Uptake in Metastatic or Locally Advanced Non-medullary Thyroid Carcinoma	NCT05507775	Non-Medullary T...	Digoxin tablet	18 Years -	Radboud University Medical Center
A Pharmacokinetic Interaction Study Between Apatinib Mesylate and Transporter Pgp Substrate Digoxin in Advanced Solid Tumor Subjects	NCT04322552	Advanced Solid ...	Apatinib Mesyla... Digoxin tablet	18 Years - 70 Years	Jiangsu HengRui Medicine Co., Ltd.
Digoxin for the Reinduction of Radioiodine Uptake in Metastatic or Locally Advanced Non-medullary Thyroid Carcinoma	NCT05507775	Non-Medullary T...	Digoxin tablet	18 Years -	Radboud University Medical Center

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