T&T: Testosterone & Tamoxifen Trial
Study Details
Study Description
Brief Summary
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| N/A |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: treatment 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
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.
|
Outcome Measures
Primary Outcome Measures
- Safety profile [At 8 weeks and follow-up through study completion, an average of 1 year]
Safety profile, defined as the number of AEs and SAEs that occur while on tamoxifen and testosterone treatment.
Secondary Outcome Measures
- AR to ER ratio [At baseline]
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).
- Treatment response [8 weeks]
Treatment response on 8 weeks FDG-PET/CT (assessed per lesion and per patient by quantitative analysis using standardized uptake values (SUV).
- Imaging and response [At 8 weeks and follow-up through study completion, an average of 1 year]
Relation between baseline imaging and tumor characteristics to treatment response.
- Adverse events based on dosages [At 8 weeks and follow-up through study completion, an average of 1 year]
Difference in adverse events between the two testosterone dosages.
Eligibility Criteria
Criteria
Inclusion Criteria:
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Male
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A history of proven ER+ (>10% of cells), AR+ (>10% of cells), and HER2- metastatic BC
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Tumor progression after at least one line of conventional endocrine therapy (tamoxifen, AI, fulvestrant, CDK4/6, ±LHRH analogue).
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Age ≥ 18 years
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Adequate hematological, renal and liver function as follows:
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Absolute neutrophil count > 1.5 x 109/L
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Platelet count >100 x 109/L
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White blood cell count >3 x 109/L
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AST and ALT <2.5 or <5.0 in case of liver metastases x upper limit of normal (ULN)
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Creatinine clearance >50mL/min
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Prothrombin time, partial thromboplastin time and INR <1.5 x ULN
- Written informed consent
Exclusion Criteria:
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History of prostate, testicular or liver cancer
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Patients already using testosterone supplements
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Patients using medication with anti-androgenic effects (e.g. spironolactone)
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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.
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Hematocrit >50%
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Patients with uncontrolled hypertension, diabetes mellitus or other significant cardiovascular morbidity.
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Patients with recent history of coronary artery disease or trombo-embolic events within 6 months prior to screening
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Severe concurrent disease, infection, co morbid condition that, in the judgment of the investigator would make the patient inappropriate for enrollment
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Visceral crisis and/or rapid progression necessitating chemotherapy
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Previous allergic reaction to androgen agonists
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Contra-indication for PET imaging
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Tamoxifen or fulvestrant treatment <5 weeks prior to FES-PET.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | UMCG | Groningen | Netherlands | 9713 GZ |
Sponsors and Collaborators
- University Medical Center Groningen
Investigators
- Principal Investigator: Geke A.P. Hospers, MD,PhD, UMCG
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 202100318