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

Primary Purpose

Non-Medullary Thyroid Carcinoma

Status
Active
Phase
Not Applicable
Locations
Netherlands
Study Type
Interventional
Intervention
Digoxin tablet
Sponsored by
Radboud University Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Non-Medullary Thyroid Carcinoma focused on measuring Thyroid cancer, Digoxin, Autophagy, Redifferentiation, Radio-iodine refractory

Eligibility Criteria

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

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.

Sites / Locations

  • Radboud University Medical Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment with digoxin

Arm Description

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

Outcomes

Primary Outcome Measures

Reinduction of radioiodine uptake in target lesion
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.

Secondary Outcome Measures

Beneficial effects of high-dose radioactive iodine treatment after reinduction
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.
Safety of digoxin treatment
All serious adverse events (SAE) occuring during the digoxin treatment will be described.

Full Information

First Posted
August 17, 2022
Last Updated
August 3, 2023
Sponsor
Radboud University Medical Center
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1. Study Identification

Unique Protocol Identification Number
NCT05507775
Brief Title
Digoxin for the Reinduction of Radioiodine Uptake in Metastatic or Locally Advanced Non-medullary Thyroid Carcinoma
Acronym
DIGUP-TC
Official Title
Digoxin for the Reinduction of Radioiodine Uptake in Metastatic or Locally Advanced Non-medullary Thyroid Carcinoma
Study Type
Interventional

2. Study Status

Record Verification Date
December 2022
Overall Recruitment Status
Active, not recruiting
Study Start Date
December 6, 2022 (Actual)
Primary Completion Date
June 21, 2023 (Actual)
Study Completion Date
January 1, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Radboud University Medical Center

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non-Medullary Thyroid Carcinoma
Keywords
Thyroid cancer, Digoxin, Autophagy, Redifferentiation, Radio-iodine refractory

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Model Description
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.
Masking
None (Open Label)
Allocation
N/A
Enrollment
10 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Treatment with digoxin
Arm Type
Experimental
Arm Description
This arm will consist of 10 patients with radioiodine refractory non-medullary thyroid carcinoma. All participants will be treated according to the same protocol.
Intervention Type
Drug
Intervention Name(s)
Digoxin tablet
Intervention Description
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.
Primary Outcome Measure Information:
Title
Reinduction of radioiodine uptake in target lesion
Description
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.
Time Frame
3 weeks
Secondary Outcome Measure Information:
Title
Beneficial effects of high-dose radioactive iodine treatment after reinduction
Description
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.
Time Frame
6 months
Title
Safety of digoxin treatment
Description
All serious adverse events (SAE) occuring during the digoxin treatment will be described.
Time Frame
3 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Facility Information:
Facility Name
Radboud University Medical Center
City
Nijmegen
Country
Netherlands

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

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