Transdermal estradiol and exercise in mitigating adverse effects of androgen deprivation therapy for prostate cancer radiation therapy (ESTRACISE)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Central Finland Hospital District Central Finland Hospital Nova

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male

Therapeutic area

Diseases [C] - Male Urogenital Diseases [C12]

Trial duration

1 Sep 2024 → ongoing

Decision date (initial)

2023-08-21

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

To estimate the efficacy of E2 in improving sexual dysfunction during ADT.

Secondary objectives 5

1. To investigate the occurrence of ADT-induced adverse effects during ADT
2. To estimate the safety and tolerability of transdermal E2 during ADT treatment of PCa
3. To estimate the impact of E2 with or without resistance training in mitigating the adverse effects of ADT on physical performance, body composition, and systematic biomarkers
4. To estimate the safety and tolerability of resistance training with or without transdermal E2 during ADT
5. To investigate the impact of transdermal E2 with or without resistance training on quality of life and perceived fatigue during ADT

Conditions and MedDRA coding

Prostate cancer

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. Men with localized PCa starting radiotherapy with adjuvant ADT at least for one year
2. Adults (age over 18 years)
3. Sufficient performance status ECOG 0-1
4. Willingness to participate and signed consent
5. Body mass index between 18.5 – 30.0

Exclusion criteria 13

1. Patients with low-risk PCa
2. Patients with expected adjuvant ADT for less than one year
3. Distant bone, lymph node, or soft tissue metastasis
4. Cardiac pacemaker
5. Diabetes Mellitus
6. Prior cardiovascular event or stroke (<12 months)
7. Past or current venous thromboembolism
8. Other untreated or unstable malignancy in risk of recurrence/progression (as judged by the treating physician)
9. Concurrent glucocorticoid treatment
10. Physical disabilities for regular exercise
11. Any medication or condition considered as a contraindication to estradiol (allergy to adjuvant compounds (carbomer, trolamine), history with thromboembolic disorders (protein C, protein S, or antithrombin deficiency), porphyria, acute or previous liver disease, drugs with cytochrome P450 enzyme metabolism (anticonvulsants: phenobarbital, phenytoin, carbamazepine; anti-infectives: rifampicin, rifapentine, nevirapine, efavirenz; and St. John's wort)) or leuprorelin (allergy to adjuvant compounds (polylactic acid), Qt-time prolonging drugs (quinidine, disopyramide, amiodarone, sotalol, dofetilide, ibutilide, methadone, moxifloxacin, antipsychotics)
12. Known allergy to estradiol or leuprorelin
13. Expected poor compliance or expected survival time of less than one year

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Primary endpoint will be the efficacy of transdermal estradiol in mitigating the sexual symptoms of ADT

Secondary endpoints 5

1. Occurrence of ADT-induced adverse effects during ADT in different study groups
2. Tolerability and safety of transdermal E2 during the one-year ADT adjuvant treatment period
3. Impact of transdermal E2 with or without 6-month resistance exercise on the muscle strength, functional capacity, body composition, lean-body muscle mass, and systematic biomarkers (g.e., blood biomarkers of and inflammatory health and muscle biomarkers)
4. Safety and tolerability of 6-month physical exercise combined with or without transdermal E2 during ADT
5. Quality of life and perceived fatigue during ADT in different study groups

Investigational products

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

Test 3

Auxiliary 4

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Central Finland Hospital District Central Finland Hospital Nova

Sponsor organisation

Central Finland Hospital District Central Finland Hospital Nova

Address

Hoitajantie 3

City

Jyvaskyla

Postcode

40620

Country

Finland

Scientific contact point

Organisation

Central Finland Hospital District Central Finland Hospital Nova

Contact name

Heikki Seikkula

Public contact point

Organisation

Central Finland Hospital District Central Finland Hospital Nova

Contact name

Heikki Seikkula

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 35 files

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

Application history

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