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Trial Title:
Transdermal Estradiol and Exercise in Mitigating Adverse Effects of Androgen Deprivation Therapy for Prostate Cancer Radiation Therapy
NCT ID:
NCT06271551
Condition:
Prostate Cancer
Conditions: Official terms:
Prostatic Neoplasms
Estrogens
Androgens
Conditions: Keywords:
Prostate cancer
Androgen deprivation therapy
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Not yet recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Intervention model description:
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.
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Transdermal estrogen
Description:
Participants (n=155) receiving transdermal estradiol for 12 months.
Arm group label:
Transdermal estradiol
Intervention type:
Drug
Intervention name:
Active Comparator: Androgen deprivation therapy
Description:
Participants (n=155) receiving solely androgen deprivation therapy for 12 months.
Arm group label:
Androgen deprivation therapy
Intervention type:
Behavioral
Intervention name:
Resistance training
Description:
Participants (n=30 in each arm) performing supervised resistance training for six months.
Arm group label:
Androgen deprivation therapy
Arm group label:
Transdermal estradiol
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.
Detailed description:
The current study is an open-label study examining a drug with known tolerability and
safety profile (phase IIA trial). The study will recruit 310 prostate cancer patients
with high-risk disease and scheduled for external beam radiation with adjuvant
subcutaneous androgen deprivation therapy, leuprorelin (LHRH agonist).
Stratified randomization (n=310) will be done in a 1:1 fashion to the transdermal
estradiol + androgen deprivation therapy arm or control arm (androgen deprivation therapy
only). Stratified randomization will be based on two covariates, which are sexual
dysfunction score and BMI. The use of the stratified randomization method will guarantee
even distribution of covariates, which could likely affect the study outcomes.
Additionally, a total of 120 participants who are willing to participate in the
supervised resistance training program and have sufficient performance status (ECOG 0-1)
will be randomized to the resistance training group or the non-training control group. A
total of 30 men from each arm will be recruited to supervised training and 30 men from
each arm the non-training control group. Participants of the ESTRACISE who do not
participate in the exercise substudy will form a non-training group (n=95 per arm). The
stratified randomization of the substudy participants in the training group or the
non-training control group will be done in a 1:1 fashion before the start of the training
period. Stratified randomization will be based on two main covariates, which are age and
the self-reported physical activity level of the participant.
ESTRACISE participants allocated to the transdermal estradiol arm will use transdermal
estradiol gel (E2) as a dose of 750 ug (EstroGel 0.6 mg/ml) in addition to androgen
deprivation therapy for 12 months. Additionally, substudy participants allocated to the
resistance training groups will be attending supervised group resistance training
sessions twice a week for six months. The resistance training will start after six months
of androgen deprivation therapy. Participants in the non-training groups are advised to
stay physically active but they will do it at their own discretion.
According to the standard treatment protocol, all participants will receive androgen
deprivation therapy as leuprorelin, subcutaneous injections at three months intervals for
a minimum of one year, and standard external beam radiation for prostate cancer with
standard clinical dosing and fractionation at the discretion of the radiation oncologist.
The research methodologies include questionnaires (expanded prostate cancer index
composition 26, world health organization quality of life brief version, and patient
health questionnaire), adverse event screening, medication compliance screening,
computerized tomography (CT) of the thigh muscle, bioimpedance analysis (BIA), 3D-imaging
of the body composition, body composition and bone mineral assessment by dual-energy
x-ray absorptiometry (DXA), strength, functional capacity, physical activity
measurements, and serum and plasma blood samples. In addition, muscle biopsies are
collected from a subset of participants allocated in the resistance training (n=60) and
non-training control groups (n=60). The primary measurement timepoints are baseline (0
months), after six months of androgen deprivation therapy, and after twelve months of
androgen deprivation therapy.
Based on prior sample size estimation of primary outcome the n=310 should be more than
adequate to detect statistically significant differences in the mean sexual domain score
between the two study arms. The true difference in the mean is expected to be 10, with a
probability (power) of 0.8, a Type 1 error probability of 0.05, and with dropout rate of
10%.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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
Gender:
Male
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Start date:
March 2024
Completion date:
December 2029
Lead sponsor:
Agency:
Central Finland Hospital District
Agency class:
Other
Collaborator:
Agency:
Tampere University
Agency class:
Other
Collaborator:
Agency:
University of Jyvaskyla
Agency class:
Other
Collaborator:
Agency:
Tampere University Hospital
Agency class:
Other
Source:
Central Finland Hospital District
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06271551
