Testosterone & Tamoxifen Trial

Study Overview
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Brief Summary
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This is a concise single arm, feasibility study, which will be executed in the University Medical Center Groningen, The Netherlands. Male patients with metastatic BC (n=6) are eligible for this study after at least 1 line of conventional endocrine therapy.

Official Title
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T&T Trial: Adding Testosterone to Tamoxifen in Male Breast Cancer Patients

Conditions
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Male Breast Cancer

Intervention / Treatment
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* Drug: AndroGel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male A history of proven ER+ (>10% of cells), AR+ (>10% of cells), and HER2- metastatic BC Tumor progression after at least one line of conventional endocrine therapy (tamoxifen, AI, fulvestrant, CDK4/6, ±LHRH analogue). Age ≥ 18 years Adequate hematological, renal and liver function as follows: Absolute neutrophil count > 1.5 x 109/L Platelet count >100 x 109/L White blood cell count >3 x 109/L AST and ALT <2.5 or <5.0 in case of liver metastases x upper limit of normal (ULN) Creatinine clearance >50mL/min Prothrombin time, partial thromboplastin time and INR <1.5 x ULN Written informed consent Exclusion Criteria: History of prostate, testicular or liver cancer Patients already using testosterone supplements Patients using medication with anti-androgenic effects (e.g. spironolactone) Elevated PSA (>4μg/L) or severe urinary tract problems (as defined with a Prostate Symptom Score >19). Patients with known BRCA mutation and PSA >3 μg/L will be referred to the urologist for prostate cancer screening, and can participate if they have no signs of prostate cancer. Hematocrit >50% Patients with uncontrolled hypertension, diabetes mellitus or other significant cardiovascular morbidity. Patients with recent history of coronary artery disease or trombo-embolic events within 6 months prior to screening Severe concurrent disease, infection, co morbid condition that, in the judgment of the investigator would make the patient inappropriate for enrollment Visceral crisis and/or rapid progression necessitating chemotherapy Previous allergic reaction to androgen agonists Contra-indication for PET imaging Tamoxifen or fulvestrant treatment <5 weeks prior to FES-PET.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Male patients with metastatic BC (n=6)
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: treatment<br>After the baseline imaging with FES- and FDHT-PET is completed, tamoxifen 20mg 1dd1 (standard dosage) plus testosterone (Androgel®) will be started. The first 3 patients will receive 25mg testosterone once daily (half the standard starting dosage for male hypogonadism). If this is well tolerated after 3 weeks, the dosage will be increased to 50mg once daily. Out of precaution, the safety profile of the 50mg dosage in the first 3 patients will be evaluated after all 3 patients have received 50mg testosterone for 2 cycli (8 weeks), prior to proceeding to the next 3 patients. Patients will be treated with tamoxifen and testosterone until disease progression or unacceptable toxicity. | Drug: AndroGel<br>* After the baseline imaging with FES- and FDHT-PET is completed, tamoxifen 20mg 1dd1 (standard dosage) plus testosterone (Androgel®) will be started. The first 3 patients will receive 25mg testosterone once daily (half the standard starting dosage for male hypogonadism). If this is well tolerated after 3 weeks, the dosage will be increased to 50mg once daily. Out of precaution, the safety profile of the 50mg dosage in the first 3 patients will be evaluated after all 3 patients have received 50mg testosterone for 2 cycli (8 weeks), prior to proceeding to the next 3 patients. Patients will be treated with tamoxifen and testosterone until disease progression or unacceptable toxicity.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety profile | Safety profile, defined as the number of AEs and SAEs that occur while on tamoxifen and testosterone treatment. | At 8 weeks and follow-up through study completion, an average of 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AR to ER ratio | AR to ER ratio on baseline FES- and FDHT-PET imaging (assessed per lesion and per patient by quantitative analysis using standardized uptake values (SUV)) and/or tumor tissue (assessed by percentage of ER and AR expression). | At baseline | 
| Treatment response | Treatment response on 8 weeks FDG-PET/CT (assessed per lesion and per patient by quantitative analysis using standardized uptake values (SUV). | 8 weeks | 
| Imaging and response | Relation between baseline imaging and tumor characteristics to treatment response. | At 8 weeks and follow-up through study completion, an average of 1 year | 
| Adverse events based on dosages | Difference in adverse events between the two testosterone dosages. | At 8 weeks and follow-up through study completion, an average of 1 year |