Hypogonadism, Prostate Cancer
Conditions
Brief summary
Androgen deprivation therapy (ADT) is a cornerstone therapy in the treatment of curable prostate cancer (PCa). However, ADT often leads to a protracted testosterone recovery period in most men or absence of complete recovery in 10-25% of cases. The hypogonadal state has significant psychosocial and physical side effects. Therefore, limiting ADT effect's duration beyond the prescribed castration period is very compelling to patients and providers alike. Tamoxifen, a well-established selective estrogen receptor modulator, offers a novel and cost-effective approach to accelerate testosterone recovery in men with secondary hypogonadism. This project addresses a critical gap in global cancer care by evaluating Tamoxifen as a viable solution for reducing the burden of delayed testosterone recovery and its associated side effects, particularly in resource-limited settings.
Interventions
DRUGTamoxifen
Selective estrogen receptor modulator, oral tablet
Sponsors
University Health Network, Toronto
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* At least 18 years of age; * Ability to understand the purposes and risks of the trial and has signed a written informed consent form. Have a diagnosis of prostate cancer; * Patient received ADT for a duration of either 6 or 18-36 months as part of the curative intent treatment. Curative intent prostate cancer patients who completed ADT and have had no further ADT for the length of the last ADT injection depot formulation (e.g., if the last ADT injection depot formulation is for 3 months, the patient must have no ADT for 3 months after last injection) * Have effectively castrated testosterone (\< 1.7 nmol/L \[50 ng/dL\]) within 6 weeks of enrollment; * ECOG Performance status 0-2
Exclusion criteria
* Harbouring certain CYP2D6 alleles (i.e. CYP2D6\*4) or from the chronic use of a CYP2D6 inhibitor(s); * History of blood clots (venous thromboembolism or pulmonary embolism); * History of stroke or transient ischemic attack (TIA); * Reduced liver function within last 120 days prior to enrolment, defined as follows: 1. Total Bilirubin: 1.5 \> upper limit of normal (ULN) (For Gilbert's syndrome, if total bilirubin is \<1.5 x ULN, measure direct and indirect bilirubin. If direct bilirubin is greater than 1.5 x ULN, participant is ineligible; 2. AST(SGOT) and ALT(SGPT): \> 2.5x ULN; 3. Or other liver disease as deemed ineligible by the investigator * Baseline QT/QTc \> 500ms; * Active therapy with selective serotonin reuptake inhibitor (SSRI) antidepressants (e.g. paroxetine, a known CYP2D6 inhibitor); * Active therapy with coumarin-type anticoagulants; * Active therapy with cytotoxic agents; * Active therapy with aromatase inhibitors; * Other invasive malignancy within the last 5 years, other than squamous or basal cell carcinoma of the skin; * Treatment with a non-approved or experimental drug during the 3 months before informed consent; * Patients known to have one of the following hereditary illnesses; galactose- intolerance, Lapp lactase deficiency or glucose-galactose malabsorption; * Any other significant concomitant disease or condition that could interfere with the conduct of the study, or that would, in the opinion of the investigator, pose an unacceptable risk to the participant in this trial;
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Normal Testosterone Recovery | 6 months after starting intervention | Proportion of participants with normal testosterone levels (i.e. total testosterone \> 7.7nmol/L \[222 ng/dL\]) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Disease Control | From enrollment to 2 years after starting treatment | Measurement of PSA levels in blood |
| Patient-Reported Toxicities | From enrollment to 2 years after starting treatment | Collection and assessment of adverse events as per PRO-CTCAE version 6.0 |
| Non-Castrated Testosterone Recovery | From enrollment to 2 years after starting treatment | Proportion of participants with non-castrated testosterone levels (i.e. 50-222 ng/dL\]) |
| Time to Testosterone Recovery | From enrollment to 2 years after starting treatment | How long it takes for participants to reach non-castrated and normal testosterone levels |
| Urinary Function (Patient-Reported Quality of Life) | From enrollment to 2 years after starting treatment | Participant completion of the EPIC-26 questionnaire |
| Bowel Function (Patient-Reported Quality of Life) | From enrollment to 2 years after starting treatment | Participant completion of the EPIC-26 questionnaire |
| Sexual Function (Patient-Reported Quality of Life) | From enrollment to 2 years after starting treatment | Participant completion of the EPIC-26 questionnaire |
| Fatigue (Patient-Reported Quality of Life) | From enrollment to 2 years after starting treatment | Participant completion of the PROMIS-Fatigue Short Form questionnaire |
| Cognitive Function (Patient-Reported Quality of Life) | From enrollment to 2 years after starting treatment | Participant completion of the FACT-Cog questionnaire |
| Depression (Patient-Reported Quality of Life) | From enrollment to 2 years after starting treatment | Participant completion of the PROMIS Emotional Distress-Depression Short Form questionnaire |
| Overall Health (Patient-Reported Quality of Life) | From enrollment to 2 years after starting treatment | Participant completion of the EQ-5D-5L questionnaire |
Countries
Canada
Contacts
CONTACTAlejandro Berlin, MD
Outcome results
None listed