Transdermal Estradiol and Exercise in Mitigating Adverse Effects of Androgen Deprivation Therapy for Prostate Cancer Radiation Therapy

NCT06271551 | Not Yet Recruiting Phase 2

• 1 other identifier: ESTRACISE
• Study Type: interventional
• Target: 310
• Locations: 0 countries
• Sites: N/A

Brief Summary

The goal of the clinical trial is to find out whether transdermal estradiol will reduce the adverse effects of androgen deprivation therapy in prostate cancer patients. The primary aim of this study is to estimate the efficacy of transdermal estradiol (E2) in reducing androgen deprivation therapy induced adverse effects on sexual function. A secondary aim of this study is to estimate the utility of E2 and the combination of E2 with supervised exercise in reducing other androgen deprivation therapy related adverse effects. Participants (n=310) will use transdermal estradiol for 12 months concomitant to androgen deprivation therapy. The use of transdermal estradiol will start at the beginning of the trial, at the same time as androgen deprivation therapy. A subgroup of participants (n=120) will also be allocated to perform six months supervised resistance training. Researchers will compare transdermal estradiol group to control group, and resistance training groups and non-training control groups.

Conditions

Prostate Cancer

Keywords

Prostate cancer; Androgen deprivation therapy

Outcome Measures

Primary Outcomes (1)

• The efficacy of transdermal estradiol in mitigating the deterioration of EPIC-26 (The Expanded Prostate Cancer Index Composite) sexual function domain scores caused by androgen deprivation therapy.

  Compared between the two arms. Scores scaled from 0 - 100, higher score means better sexual function.

  Twelve and six months.

Secondary Outcomes (17)

• The occurrence of androgen deprivation therapy induced adverse effects.

  Twelve and six months.

• Number of participants with transdermal estradiol-related adverse events as assessed by CTCAE (Common Terminology Criteria for Adverse Events).

  Twelve and six months.

• Impact of transdermal estradiol with or without 6-month supervised resistance training on one repetition maximum tests of both the leg press and barbell biceps curl, and maximal hand grip strength assessed with a dynamometer.

  Twelve and six months.

• Impact of transdermal estradiol with or without 6-month supervised resistance training on explosive strength of the leg extensors assessed with a countermovement jump (CMJ).

  Twelve and six months.

• Impact of transdermal estradiol with or without 6-month supervised resistance training on 6-minute walk (functional capacity).

  Twelve and six months.

Study Arms (2)

Transdermal estradiol

EXPERIMENTAL

Participants (n=155) receiving transdermal estradiol and androgen deprivation therapy.

Drug: Transdermal estrogen; Behavioral: Resistance training

Androgen deprivation therapy

ACTIVE COMPARATOR

Participants (n=155) receiving solely androgen deprivation therapy.

Drug: Active Comparator: Androgen deprivation therapy; Behavioral: Resistance training

Interventions

Transdermal estrogen DRUG

Participants (n=155) receiving transdermal estradiol for 12 months.

Transdermal estradiol

Active Comparator: Androgen deprivation therapy DRUG

Participants (n=155) receiving solely androgen deprivation therapy for 12 months.

Androgen deprivation therapy

Resistance training BEHAVIORAL

Participants (n=30 in each arm) performing supervised resistance training for six months.

Androgen deprivation therapy; Transdermal estradiol

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Men with localized prostate cancer, and scheduled for external beam radiation with adjuvant subcutaneous androgen deprivation therapy, leuprorelin (LHRH agonist) for at least 12 months without any other endocrinology treatments for prostate cancer
• Adults (age over 18 years)
• Sufficient performance status (Eastern Cooperative Oncology Group, 0-1)
• Body mass index between 18.5 - 30.0
• Willingness to participate and signed consent

You may not qualify if:

• Patients with low-risk prostate cancer (ISUP Gleason grade 1)
• Patients with expected adjuvant androgen deprivation therapy for less than one year
• Distant bone, lymph node, or soft tissue metastasis
• Cardiac pacemaker
• Prior recent cardiovascular event or stroke (\<12 months)
• Past or current venous thromboembolism
• Other untreated or unstable malignancy in risk of recurrence/progression (as judged by the treating physician)
• Concurrent glucocorticoid treatment
• Physical disabilities for regular exercise
• 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)
• Known allergy to estradiol or leuprorelin
• Expected poor compliance or expected survival time of less than one year

Sponsors & Collaborators

• Central Finland Hospital District: lead
• Tampere University: collaborator
• University of Jyvaskyla: collaborator
• Tampere University Hospital: collaborator

Related Publications (1)

• Jussila I, Ahtiainen JP, Laakkonen EK, Siltari A, Kaipia A, Jokela T, Karkkainen M, Newton R, Raastad T, Huhtala H, Murtola TJ, Seikkula H. Transdermal oestradiol and exercise in androgen deprivation therapy (ESTRACISE): protocol. BJU Int. 2024 Jul;134(1):110-118. doi: 10.1111/bju.16361. Epub 2024 Apr 8.

  PMID: 38587276 DERIVED

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

Resistance Training

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Exercise Therapy; Rehabilitation; Aftercare; Continuity of Patient Care; Patient Care; Therapeutics; Physical Therapy Modalities; Physical Conditioning, Human; Exercise; Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena

Central Study Contacts

Heikki Seikkula, MD, Docent

CONTACT

+358142691299; heikki.seikkula@hyvaks.fi

Ilkka Jussila, MSc.

CONTACT

+358142694546; ilkka.jussila@outlook.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Participants are randomized in a 1:1 fashion to receive transdermal estradiol and androgen deprivation or solely androgen deprivation therapy. In addition subgroup of participants are randomized in a 1:1 fashion to perform resistance training or to be allocated in non-training control group.

Study Record Dates

• First Submitted: November 20, 2023
• First Posted: February 21, 2024
• Study Start: March 1, 2024
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 1, 2029
• Last Updated: February 21, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will not share