Digoxin for the Reinduction or Radioiodine Uptake in Metastatic or Locally Advanced Non-medullary Thyroid Cancer.

Phase 1

• Conditions: on-medullary thyroid Carconoma (NMTC); MedDRA version: 21.1Level: PTClassification code: 10055107Term: Thyroid cancer metastatic Class: 100000004864; Therapeutic area: Diseases [C] - Neoplasms [C04]

• Registration Number: CTIS2022-500477-14-00
• Lead Sponsor: Stichting Radboud University Medical Center

Brief Summary

Summary of Results

Detailed Description

Not available

Study Timeline

• Study Start: 2022-06-09
• Study Completion: 2023-06-21
• Last Update Posted: 21 August 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 10

Inclusion Criteria

Being diagnosed with NMTC., Being aged =18 years., Having undergone total thyroidectomy and at least 1 treatment with RaI., The presence of local or metastatic disease, radiologically proven. A minimum of 1 target lesion (minimum of 1.0 cm for soft tissue and 1.5 cm for lymph nodes) must be present., RaI refractory disease: at least one lesion (target lesion, needs to fulfil the above-mentioned criteria) without therapeutic relevant RaI uptake at previous post-therapeutic RaI scintigraphy and/or negative diagnostic RaI scan., Target lesion must not be eligible for local treatments (radiotherapy, radiofrequency ablation, etc.). In case of multiple lesions, local treatment is allowed, but these lesions are not considered target lesions.

Exclusion Criteria

Contraindications for digoxin: Creatinine clearance < 50 ml/min and/or active kidney disease; Cardiac arrhythmias (history of arrhythmias and arrhythmias at ECG); Electrolyte disorders, Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection or psychiatric illness/social situations that would limit compliance with study requirements., Unwillingness or inability to comply with study and follow-up procedures., Condition of patient which is critical to participate in this study in the discretion of the PI., Rapidly progressive disease in which urgent start with systemic therapy is required., Concomitant drugs that interfere with digoxin metabolism such as P-glycoprotein inductors or inhibitors, including but not limited to penicillamin, sufasalazin, tipranavir, amiodaron, diltiazem, itraconazol, ketoconazol, kinidin, lapatinib, propafenon, vemurafenib, verapamil, azitromycin, claritromycin, erythromycin, roxitromycin, chloroquin, ciclosporin, anti HCV drugs, anti-HIV drugs, hydroxychloroquine., Patients who do not have normal organ and bone marrow function as defined below: Absolute neutrophil count (ANC) >1.5x109/L; Hemoglobin = 9 g/dL; Platelets = 100 x 109/L., Other active malignancies other than basal cell carcinoma. Malignancies that have been in complete remission for >2 years are not considered active malignancies., Pregnancy, lactating or breast-feeding women. Negative pregnancy test is mandatory within 7 days prior to starting the study premenopausal women. Women of non-childbearing potential may be included without pregnancy test if they are either surgically sterile or have been postmenopausal for = 1 year. Fertile men and women must use an effective method of contraception during treatment and for at least 6 months after completion of treatment as directed by their physician. Effective methods of contraception are defined as those, which result in a low failure rate (i.e., less than 1% per year) when used consistently and correctly (for example implants, injectables, combined oral contraception or intra-uterine devices). At the discretion of the investigator, acceptable methods of contraception may include total abstinence in cases where the lifestyle of the patient ensures compliance. (Periodic abstinence [e.g., calendar, ovulation, symptothermal, postovulation methods] and withdrawal are not acceptable methods of contraception)., Having undergone a CT-scan with contrast agent within the last three months (this would reduce the iodide uptake)., Prior therapy with 131I <6 months prior to initiation of therapy on this protocol. A diagnostic study using <400 MBq of 131I is not considered 131I-therapy., External beam radiation therapy < 4 weeks prior to initiation of therapy on this protocol. (Previous treatment with radiation for any indication is allowed if the investigator judges that the previous radiation does not significantly compromise patient safety on this protocol)., Chemotherapy or targeted therapy (e.g., tyrosine kinase inhibitor) is not allowed < 4 weeks prior to the initiation of therapy on this protocol., Eastern Cooperative Oncology Group (ECOG) score >2., Use of other investigational drugs within 4 weeks preceding the first dose of drug treatment during this study., A known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to the investigational drug.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: The primary objective is to study the beneficial effects of digoxin in patients with non-medullary thyroid carcinoma (NMTC) with locally advanced or metastatic disease with insufficient accumulation of RaI on reinduction of RaI uptake.;Secondary Objective: The secondary objective is to study the beneficial effects of RaI therapy on tumor progression after reinduction of RaI uptake with digoxin and to assess safety of digoxin treatment., An explorative objective is to evaluate alterations in responding and non-responding tumor lesions after re-differentiation treatment on transcriptional and translational level and assessment of autophagy activity in primary tumors and target lesions if material is available.;Primary end point(s): The number and percentage of subjects in whom there is reinduction of RaI uptake in RaI refractory target lesions. This will be assessed using RaI scintigraphy.

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s):The proportion of subjects with a favorable response to RaI treatment after 6 months, according to RECIST criteria.;Secondary end point(s):Biochemical response to RaI treatment after 6 months, measured by thyroglobulin (TG).;Secondary end point(s):Toxicity assessment using CTAE criteria v4.0.;Secondary end point(s):Quality of life using EORTC QLQ-C30.;Secondary end point(s):oCorrelations between molecular pattern in pre-treatment biopsies (if available) and other study endpoints.