Trial document

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Trial Description

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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

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Trial Acronym


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URL of the Trial


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Brief Summary in Lay Language

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, rando¬mised 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.

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Brief Summary in Scientific Language


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Organizational Data

  •   DRKS00004500
  •   2012/11/30
  •   2012/07/09
  •   yes
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Secondary IDs

  •   2009-015122-11 
  •   NCT01638247  (
  •   GBG 54  (German Breast Group)
  •   2009-015122-11 
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Health Condition or Problem studied

  •   Male Breast Cancer
  •   C50 -  Malignant neoplasm of breast
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Interventions/Observational Groups

  •   Drug: Tamoxifen
  •   Drug: Tamoxifen and GnRH analogue
  •   Drug: Exemestane and GnRH analogue
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  •   Interventional
  •   [---]*
  •   Randomized controlled trial
  •   Open (masking not used)
  •   [---]*
  •   Active control
  •   Treatment
  •   Parallel
  •   III
  •   [---]*
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Primary Outcome

- Estradiol blood concentation; time frame: 3 months.; To determine the estradiol suppression between the three treatment arms after three months.

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Secondary Outcome

- 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).

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Countries of Recruitment

  •   Germany
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Locations of Recruitment

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  •   [---]*
  •   2012/08/31
  •   48
  •   Multicenter trial
  •   National
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Inclusion Criteria

  •   Male
  •   18   Years
  •   85   Years
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Additional Inclusion Criteria

1. Written informed consent for all study procedures.

2. Complete baseline documentation sent to GBG Forschungs GmbH.

3. Male patients.

4. Age ≥ 18 years.

5. Karnofsky-Index ≥ 60%.

6. Histologically confirmed unilateral or bilateral carcinoma or DCIS of the breast at
primary diagnosis (enrolment possible in neoadjuvant, adjuvant and metastatic

7. Positive hormone receptor status (e.g. ER and/or PR-receptor positive).

8. Completed staging prior randomisation (≤ 28 days, minimum: chest X-ray, ultrasound of
the liver, bone scan).

In case of positive findings, further investigations are required to verify the
findings as clinically indicated.

9. Prior chemotherapy is possible. In case of adjuvant treatment: adequate surgical
treatment with histological complete resection including axillary lymph nodes if
patients are included as adjuvant treatment. A sentinel lymph node biopsy is possible
if the sentinel is not involved.

10. Normal cardiac function must be confirmed by ECG within three months prior to

11. Laboratory requirements (≤ 7 days before therapy start):


- Hemoglobin ≥ 9 g/dL,

- Leukocytes 4 - 10 x103/µL,

- Thrombocytes 150 - 400 x103/µL. Hepatic function

- ASAT (SGOT) or ALAT (SGPT) ≤ 1.5x UNL,

- Total bilirubin ≤ 1.5x UNL. Renal function

- Serum creatinine ≤ 1.5x UNL,

- Creatinine clearance > 30mL/min (if creatinine is above UNL, according to

- Cholesterol 200 - 240 mg/dL (5.18 - 6.22 mmol/L),

- HDL cholesterol > 40 mg/dL (> 1 mmol/L),

- LDL cholesterol ≤ 160 mg/dL (≤ 4 mmol/L).

- Prostate specific antigen (PSA) ≤ 2.5 ng/mL.

12. Two serum samples (5 mL) centrally made available.

13. Paraffin tumor tissue block and full blood sample centrally made available (except
when the patient does not agree to central biomaterial collection).

14. The patient must be accessible for treatment.

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Exclusion Criteria

1. Female patients.

2. Prior endocrine therapy of breast carcinoma.

3. Known or suspected hypersensitivity reaction to the compounds or incorporated

4. No indication for endocrine treatment.

5. Life expectancy of less than six months.

6. International Prostate Symptom Score (IPSS) > 17.

7. Prostate carcinoma or PSA > 2.5 ng/mL.

8. History of prostate cancer within the last five years and regardless the time frame
all patients with hormone receptor positive prostate carcinoma who have received
endocrine treatment.

9. Concurrent neuronal or cardiac disease, poorly controlled arterial hypertension.

10. Previous thromboembolic event within the last five years.

11. Currently active hepatitis.

12. Disease significantly affecting gastrointestinal function, e.g. malabsorption
syndrome, resection of the stomach or small bowel, ulcerative colitis.

13. Concurrent treatment with other experimental drugs or participation in another
clinical trial with any investigational, not marketed drug within 30 days prior to
study entry.

14. Patients who are not able to give informed consent as defined according to AMG
(German Drug Law).

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  • start of 1:1-Block address primary-sponsor
    • German Breast Group
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    • Pfizer
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    •   [---]*
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    • GBG Forschungs GmbH
    • Sibylle Loibl, MD 
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    • Mathias Uhlig, Ph.D. 
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Sources of Monetary or Material Support

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    • Bitte wenden Sie sich an den Sponsor / Please refer to primary sponsor
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    •   [---]*
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  •   Recruiting ongoing
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Trial Publications, Results and other Documents

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The parameters in and DRKS are not identical. Therefore the data import from required adjustments. For full details please see the DRKS FAQs .
  •   3
  •   2013/10/30
* This entry means the parameter is not applicable or has not been set.