Clinical Trial to Observe the Effects of Tamoxifen on Testosterone Recovery in Medically Castrated Prostate Cancer Patients (REVIVE)

Phase II Controlled Clinical Trial to Test Efficacy and Observe Longitudinal Effects of Tamoxifen for Testosterone Recovery in Medically Castrated Prostate Cancer Patients

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Prostate Cancer; Hypogonadism
• Intervention / Treatment: Drug: Tamoxifen

• Study Type: Interventional
• Enrollment (Estimated): 96
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Alejandro Berlin, MD; Phone Number: 5813 416-946-4501; Email: alejandro.berlin@uhn.ca

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 2M9
      • University Health Network - Princess Margaret Cancer Center
      • Contact: Alejandro Berlin, MD; Phone Number: 5813 416-946-4501; Email: alejandro.berlin@uhn.ca

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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;

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Non-Experimental Intervention: Observation; Participant will not receive intervention after treatment with ADT. Per routine care, participant will undergo observation for testosterone recovery
Experimental: Experimental Intervention: Tamoxifen; Participant will take 2 tamoxifen pills by mouth, every day, for a total of 40 mg each day. The duration of tamoxifen treatment will depend on the duration of the participant's previous ADT treatment. If the participant received ADT treatment for 6 months, they will receive daily Tamoxifen for 3 months. If the participant received ADT treatment for 18-36 months, they will receive daily Tamoxifen for 6 months.	Drug: Tamoxifen; Selective estrogen receptor modulator, oral tablet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Normal Testosterone Recovery	Proportion of participants with normal testosterone levels (i.e. total testosterone > 7.7nmol/L [222 ng/dL])	6 months after starting intervention

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease Control	Measurement of PSA levels in blood	From enrollment to 2 years after starting treatment
Patient-Reported Toxicities	Collection and assessment of adverse events as per PRO-CTCAE version 6.0	From enrollment to 2 years after starting treatment
Non-Castrated Testosterone Recovery	Proportion of participants with non-castrated testosterone levels (i.e. 50-222 ng/dL])	From enrollment to 2 years after starting treatment
Time to Testosterone Recovery	How long it takes for participants to reach non-castrated and normal testosterone levels	From enrollment to 2 years after starting treatment
Urinary Function (Patient-Reported Quality of Life)	Participant completion of the EPIC-26 questionnaire	From enrollment to 2 years after starting treatment
Bowel Function (Patient-Reported Quality of Life)	Participant completion of the EPIC-26 questionnaire	From enrollment to 2 years after starting treatment
Sexual Function (Patient-Reported Quality of Life)	Participant completion of the EPIC-26 questionnaire	From enrollment to 2 years after starting treatment
Fatigue (Patient-Reported Quality of Life)	Participant completion of the PROMIS-Fatigue Short Form questionnaire	From enrollment to 2 years after starting treatment
Cognitive Function (Patient-Reported Quality of Life)	Participant completion of the FACT-Cog questionnaire	From enrollment to 2 years after starting treatment
Depression (Patient-Reported Quality of Life)	Participant completion of the PROMIS Emotional Distress-Depression Short Form questionnaire	From enrollment to 2 years after starting treatment
Overall Health (Patient-Reported Quality of Life)	Participant completion of the EQ-5D-5L questionnaire	From enrollment to 2 years after starting treatment

Collaborators and Investigators

• Sponsor: University Health Network, Toronto

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2026
• Primary Completion (Estimated): October 1, 2030
• Study Completion (Estimated): October 1, 2030

Study Registration Dates

• First Submitted: March 27, 2026
• First Submitted That Met QC Criteria: April 14, 2026
• First Posted (Actual): April 17, 2026

Study Record Updates

• Last Update Posted (Actual): April 17, 2026
• Last Update Submitted That Met QC Criteria: April 14, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Endocrine System Diseases; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Prostatic Diseases; Male Urogenital Diseases; Gonadal Disorders; Prostatic Neoplasms; Hypogonadism; Organic Chemicals; Hydrocarbons; Hydrocarbons, Cyclic; Hydrocarbons, Aromatic; Benzene Derivatives; Stilbenes; Benzylidene Compounds; Tamoxifen
• Other Study ID Numbers: 25-5742

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No