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.

Inclusion Criteria:

• Non-medullary thyroid carcinoma
• Having undergone total thyroidectomy and at least 1 treatment with [131]sodium iodine (NaI)
• Presence of local or metastatic disease, radiologically proven. A minimum of 1 target lesion (at least 1cm for soft tissue and 1.5cm for lymph nodes) must be present.
• Radioiodine refractory disease; at least one lesion without therapeutic relevant uptake at previous post-therapeutic scintigraphy and/or negative diagnostic [123]NaI-scan.
• The target lesion must not be eligible for local treatments.
• Hematologic lab values should be at least: absolute neutrophil count >1.4x10^9/liter, hemoglobin>5.5mmol/liter, thrombocytes >99x10^9/liter

Exclusion Criteria:

• Creatinine clearance <50ml/min and/or active kidney disease
• Cardiac arrhythmias
• Electrolyte disorder
• Concomitant drugs that interfere with digoxin metabolism such as P-glycoprotein inductors or inducers, including but not limited to penicillamine, sulfasalazin, tipranavir, amiodarona, diltiazem, itraconazole, ketoconazole, kinidin, lapatinib, propafenon, vemurafenib, verapamil, azithromycin, clarithromycin, erythromycin, roxithromycin, chloroquin, ciclosporin, anti hepatitis C drugs, anti-HIV drugs, hydroxychloroquine.
• Pregnancy, lactating or breast-feeding women.
• Having undergone a procedure with iodine contrast agent within the last 3 months.
• Prior therapy with radioactive iodine <6 months prior to participation.
• External beam radiation therapy <4 weeks prior to participation.
• Having undergone chemotherapy or targeted therapy <4 weeks prior to participation.
• Eastern Cooperative Oncology Group (ECOG) score >2.
• Use of other investigational drugs within 4 weeks preceding the first dose of digoxin treatment.
• Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to digoxin.
• Uncontrolled intercurrent illness that would limit compliance with the study requirements.
• Unwillingness or inability to comply with study and follow-up procedures.
• Other active malignancies other than basal cell carcinoma. Malignancies that have been in complete remission over 2 years are not considered active malignancies.
• Rapidly progressive disease in which urgent start with systemic therapy is required.