Testosterone & Tamoxifen Trial (T&T)

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Male Breast Cancer
• Intervention / Treatment: Drug: AndroGel

• Study Type: Interventional
• Enrollment (Actual): 5
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Geke A.P Hospers, MD,PhD; Phone Number: +31503612821; Email: g.a.p.hospers@umcg.nl
• Study Contact Backup: Name: Jasper J.L. van Geel, MD; Phone Number: +31503616161; Email: j.j.l.van.geel@umcg.nl

Study Locations

• Netherlands
  • Groningen, Netherlands, 9713 GZ
    • UMCG

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Male
2. A history of proven ER+ (>10% of cells), AR+ (>10% of cells), and HER2- metastatic BC
3. Tumor progression after at least one line of conventional endocrine therapy (tamoxifen, AI, fulvestrant, CDK4/6, ±LHRH analogue).
4. Age ≥ 18 years

5. 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
6. Written informed consent

Exclusion Criteria:

1. History of prostate, testicular or liver cancer
2. Patients already using testosterone supplements
3. Patients using medication with anti-androgenic effects (e.g. spironolactone)
4. 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.
5. Hematocrit >50%
6. Patients with uncontrolled hypertension, diabetes mellitus or other significant cardiovascular morbidity.
7. Patients with recent history of coronary artery disease or trombo-embolic events within 6 months prior to screening
8. Severe concurrent disease, infection, co morbid condition that, in the judgment of the investigator would make the patient inappropriate for enrollment
9. Visceral crisis and/or rapid progression necessitating chemotherapy
10. Previous allergic reaction to androgen agonists
11. Contra-indication for PET imaging
12. Tamoxifen or fulvestrant treatment <5 weeks prior to FES-PET.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University Medical Center Groningen
• Investigators: Principal Investigator: Geke A.P. Hospers, MD,PhD, UMCG

Study record dates

Study Major Dates

• Study Start (Actual): November 10, 2022
• Primary Completion (Estimated): October 3, 2024
• Study Completion (Estimated): October 3, 2024

Study Registration Dates

• First Submitted: November 16, 2021
• First Submitted That Met QC Criteria: November 30, 2021
• First Posted (Actual): December 14, 2021

Study Record Updates

• Last Update Posted (Estimated): April 30, 2024
• Last Update Submitted That Met QC Criteria: April 29, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Breast Neoplasms, Male; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Androgens; Testosterone
• Other Study ID Numbers: 202100318

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No