Evaluation of metformin effect on the fertility of women treated with 131Ifor thyroid cancer

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Medical University Of Bialystok

Participant type

Patients

Age range

18-64 years

Gender

Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

9 Nov 2022 → ongoing

Decision date (initial)

2024-12-03

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Medical Research Agency

External identifiers

EU CT number

2024-518352-23-00

EudraCT number

2021-005366-17

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Therapy

To evaluate the efficacy of metformin on female fertility who were subjected to 131l treatment – ovarian reserve which is shown as AMH, inhibin B and FSH level in serum and antral follicle count checked by ultrasound

Secondary objectives 3

1. Safety Objectives: Incidence of adverse events (AEs) and serious adverse events (SAEs) and changes in laboratory measurements
2. Exploratory objectives: Patient reported outcome (ePRO) for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaires – QLQ-THY34
3. Exploratory objectives: Medical Resource Utilization (MRU)

Conditions and MedDRA coding

papillary thyroid carcinoma

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. Female subjects in reproductive age >18 <45.
2. Subjects with diagnosed papillary thyroid carcinoma with various pathological stage TNM (I-II).
3. Subjects not treated with 131I.
4. Willingness to comply with protocol procedures.

Exclusion criteria 17

1. Hypersensitivity to metformin.
2. Subjects with polycystic ovarian syndrome or other diseases of the ovaries (primary / secondary ovarian failure).
3. Subjects taking metformin during last week.
4. Subjects with liver malfunction and abnormal hepatitis marker results (ALT and AST activity >3ULN.
5. Subjects with eGFR below 45ml/min/1.73m2.
6. Subjects with lactic acidosis or having history of metabolic acidosis.
7. Subjects with serum AMH concentration below lower range norm.
8. Subjects with history of congestive heart disease NYHA stage III/IV.
9. Subjects with acute myocardial ischemia (CCS 3-4).
10. Subjects with history of sepsis or severe infection.
11. Subject with lung disease (uncontrolled asthma based on GINA 2000 Guidelines and COPD GOLD ≥ 3 stage).
12. Positive result of pregnancy test or pregnancy planned during the study.
13. Alcohol or other substance dependent syndromes.
14. BMI <18.5 kg/m2.
15. Accompanying diseases with poor prognosis in the opinion of the researcher.
16. As per Investigator (or his designee) judgement, subject cannot participate in the study due to reasons (i.e. medical, psychiatric and/or social reason).
17. Unreliability or lack of cooperation.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary endpoint will be to evaluate the effect of metformin on the difference in serum AMH, inhibin B and FSH concentration and the number of antral follicles, assessed in the study groups consisted of the women with papillary thyroid cancer, treated with 131I, comparing received results during the randomized, V3, V4, V5 and V6 visits.

Secondary endpoints 7

1. To evaluate the metformin modulating impact on the concentrations of selected parameters of oxidative stress assessed in the study groups consisted of the women with papillary thyroid cancer, treated with 131I, comparing received results during the randomized, V3, V4, V5 and V6 visits.
2. To evaluate the effect of metformin on the difference in serum concentration of selected parameters of apoptosis between the study groups in women with papillary thyroid cancer, treated with 131I, comparing received results during the randomized, V3, V4, V5 and V6 visits
3. To evaluate the effect of metformin on the difference of expression in selected microRNA between the study groups in women with papillary thyroid cancer, treated with 131I, between the randomized visit and V3, V4, V5 and V6 visit
4. Assessment of the quality of life using the QLQ-THY34 questionnaire dedicated to patients with thyroid cancer.
5. Characteristics and tolerability of standard metformin dosage in patient with papillary thyroid cancer.
6. Frequency of AEs requiring discontinuation of study drug or dose reduction.
7. Change in basic laboratory assessment between visits.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Medical University Of Bialystok

Sponsor organisation

Medical University Of Bialystok

Address

Ul. Jana Kilinskiego 1

City

Bialystok

Postcode

15-089

Country

Poland

Scientific contact point

Organisation

Medical University Of Bialystok

Contact name

Department of Endocrinology, Diabetology and Internal Medicine

Public contact point

Organisation

Medical University Of Bialystok

Contact name

Department of Endocrinology, Diabetology and Internal Medicine

Third parties 2

Locations

1 EU/EEA country · 4 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 9 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications