Tamoxifen +/- GnRH Analogue vs Aromatase Inhibitor + GnRH Analogue in Male Breast Cancer Patients (MALE)
|Male Breast Cancer||Drug: Tamoxifen Drug: Tamoxifen and GnRH analogue Drug: Exemestane and GnRH analogue||Phase 3|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Prospective, Randomised, Multi-centre Phase II Study Evaluating the Adjuvant, Neoadjuvant or Palliative Treatmant With Tamoxifen +/- GnRH Analogue Versus Aromatase Inhibitor + GnRH Analogue in Male Breast Cancer Patients|
- Estradiol blood concentation [ Time Frame: 3 months. ]To determine the estradiol suppression between the three treatment arms after three months.
- Estradiol blood concentration [ Time Frame: 6 months. ]To determine the estradiol suppression between the three treatment arms after six months.
- Compliance [ Time Frame: 6 months. ]To compare the compliance in the three treatment arms.
- Efficacy [ Time Frame: 6 months. ]To compare the efficacy in terms of overall response (for neoadjuvant and metastatic patients) in the three treatment arms.
- Efficacy perameters [ Time Frame: 6 months. ]To compare testosterone, dihydrotestosterone (DHT), SHBG, FSH, LH, osteocalcin and CTX in the three treatments arms.
- Safety and side effect parameters [ Time Frame: 6 months. ]
To determine the safety and side effect parameters (at every visit):
- PSA and hemoglobin.
- Lipids (total cholesterol, high density lipid cholesterol, low density lipid cholesterol).
|Study Start Date:||August 2012|
|Estimated Study Completion Date:||March 2018|
|Estimated Primary Completion Date:||March 2018 (Final data collection date for primary outcome measure)|
Active Comparator: Tamoxifen
Tamoxifen alone (daily).
25 mg daily.
Experimental: Tamoxifen and GnRH analogue
Tamoxifen (daily) + GnRH analogue (at randomisation and after three months).
Drug: Tamoxifen and GnRH analogue
25 mg Tamoxifen daily and GnRH analogue:
Other Name: TRENATONE, ZOLADEX
Experimental: Exemestane and GnRH analogue
Exemestane (daily) + GnRH analogue (at randomisation and after three months).
Drug: Exemestane and GnRH analogue
25 mg Exemestane daily and GnRH analogue:
Other Name: AROMASIN, TRENATONE, ZOLADEX.
Breast cancer in men is a rare disease with approximately 0.5- 1% of all breast cancer cases. Each year, about 400 to 450 cases are diagnosed in Germany. Men tend to present with more advanced disease than women, probably due to the lack of awareness of male breast cancer from both, the patient and the physicians.
Therefore, at presentation they usually have lump or nipple inversion, and more than 40% of the patients have a stage III or IV disease. The great majority of patients have an invasive ductal (90%), hormone receptor positive (90%), HER2 negative (90%) tumor.
The only available information on adjuvant therapies derives from few retrospective cases and retrospective studies with a little number of cases. Therefore, treatment strategies are not based on data from prospective, randomised clinical studies, and optimal treatment is unknown. As a result, current clinical management is generally extrapolated from principles established for the treatment of female breast carcinoma. As the majority of male breast cancer patients have a hormone receptor positive tumor, they receive tamoxifen 20 mg for five years as standard endocrine adjuvant therapy. A lot of withdrawals from the treatment were documented in male breast cancer due to side-effects under tamoxifen therapy. Furthermore, the clinical outcome of tamoxifen-treated male breast cancer patients may be influenced by the activity of cytochrome P450 2D6 enzymes that catalyse the formation of anti-estrogenic metabolites endoxifen and 4-hydroxy-tamoxifen. Therefore a significant proportion of poor to moderate metaboliser is proposed to do not benefit from adjuvant tamoxifen therapy.
Although women benefit from adjuvant treatment with aromatase inhibitors (AI) regarding disease-free-survival, overall survival and treatment toxicity, only case reports of men treated with AI exist. Other data show, that under AI, there is only a suppression of estradiol of about 40-50% with an increase of testosterone of about 50%. Among men on AIs, it is possible that the hypothalamic-pituitary feedback loop results in an increase substrate for aromatisation, and thus prevents complete estrogen suppression.
However, an optimal suppression (80%) of the peripheral estradiol level would be a necessary condition for a therapeutic benefit of AI in men with breast cancer.
By adding a gonadotropin-releasing hormone analogue, the negative feedback loop would be interrupted and complete estrogen suppression may be achieved.
In conclusion, there is a great lack on information for the treatment of male patients with breast cancer.
Prospective multi-centre, randomised trials in men with breast cancer are necessary in order to prove the effect of tamoxifen + GnRH analogue versus none and versus AI + GnRH analogue as adjuvant or neoadjuvant endocrine treatment.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01638247
|Contact: Mathias Uhlig, Ph.D.||+49-6102-7480 ext firstname.lastname@example.org|
|Contact: Konstantin Reißmüller||+49-6102-7480 ext email@example.com|
|Offenbach, Hessen, Germany, 63069|
|Contact: Sibylle Loibl, MD +49-6102-7480 ext 426 firstname.lastname@example.org|
|Sub-Investigator: Sibylle Loibl, MD|
|Principal Investigator:||Sibylle Loibl, MD||GBG Forschungs GmbH|