Trial document





This study has been imported from ClinicalTrials.gov without additional data checks.
drksid header

  DRKS00004500

Trial Description

start of 1:1-Block title

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

end of 1:1-Block title
start of 1:1-Block acronym

Trial Acronym

MALE

end of 1:1-Block acronym
start of 1:1-Block url

URL of the Trial

[---]*

end of 1:1-Block url
start of 1:1-Block public summary

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.

end of 1:1-Block public summary
start of 1:1-Block scientific synopsis

Brief Summary in Scientific Language

[---]*

end of 1:1-Block scientific synopsis
start of 1:1-Block organizational data

Organizational Data

  •   DRKS00004500
  •   2012/11/30
  •   2012/07/09
  •   yes
  •   [---]*
  •   [---]*
end of 1:1-Block organizational data
start of 1:n-Block secondary IDs

Secondary IDs

  •   2009-015122-11 
  •   NCT01638247  (ClinicalTrials.gov)
  •   GBG 54  (German Breast Group)
  •   2009-015122-11 
end of 1:n-Block secondary IDs
start of 1:N-Block indications

Health Condition or Problem studied

  •   Male Breast Cancer
  •   C50 -  Malignant neoplasm of breast
end of 1:N-Block indications
start of 1:N-Block interventions

Interventions/Observational Groups

  •   Drug: Tamoxifen
  •   Drug: Tamoxifen and GnRH analogue
  •   Drug: Exemestane and GnRH analogue
end of 1:N-Block interventions
start of 1:1-Block design

Characteristics

  •   Interventional
  •   [---]*
  •   Randomized controlled trial
  •   Open (masking not used)
  •   [---]*
  •   Active control
  •   Treatment
  •   Parallel
  •   III
  •   [---]*
end of 1:1-Block design
start of 1:1-Block primary endpoint

Primary Outcome

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

end of 1:1-Block primary endpoint
start of 1:1-Block secondary endpoint

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).

end of 1:1-Block secondary endpoint
start of 1:n-Block recruitment countries

Countries of Recruitment

  •   Germany
end of 1:n-Block recruitment countries
start of 1:n-Block recruitment locations

Locations of Recruitment

  •  
end of 1:n-Block recruitment locations
start of 1:1-Block recruitment

Recruitment

  •   [---]*
  •   2012/08/31
  •   48
  •   Multicenter trial
  •   National
end of 1:1-Block recruitment
start of 1:1-Block inclusion criteria

Inclusion Criteria

  •   Male
  •   18   Years
  •   85   Years
end of 1:1-Block inclusion criteria
start of 1:1-Block inclusion criteria add

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
situation).

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
randomisation.

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

Hematology

- 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
Cockroft-Gault).

- 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.

end of 1:1-Block inclusion criteria add
start of 1:1-Block exclusion criteria

Exclusion Criteria

1. Female patients.

2. Prior endocrine therapy of breast carcinoma.

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

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).

end of 1:1-Block exclusion criteria
start of 1:n-Block addresses

Addresses

  • start of 1:1-Block address primary-sponsor
    • German Breast Group
    end of 1:1-Block address primary-sponsor
    start of 1:1-Block address contact primary-sponsor
    •   [---]*
    •   [---]*
    •   [---]*
    •   [---]*
    end of 1:1-Block address contact primary-sponsor
  • start of 1:1-Block address other
    • Pfizer
    end of 1:1-Block address other
    start of 1:1-Block address contact other
    •   [---]*
    •   [---]*
    •   [---]*
    •   [---]*
    end of 1:1-Block address contact other
  • start of 1:1-Block address scientific-contact
    • GBG Forschungs GmbH
    • Sibylle Loibl, MD 
    end of 1:1-Block address scientific-contact
    start of 1:1-Block address contact scientific-contact
    •   [---]*
    •   [---]*
    •   [---]*
    •   [---]*
    end of 1:1-Block address contact scientific-contact
  • start of 1:1-Block address public-contact
    • Mathias Uhlig, Ph.D. 
    end of 1:1-Block address public-contact
    start of 1:1-Block address contact public-contact
    end of 1:1-Block address contact public-contact
end of 1:n-Block addresses
start of 1:n-Block material support

Sources of Monetary or Material Support

  • start of 1:1-Block address materialSupport
    • Bitte wenden Sie sich an den Sponsor / Please refer to primary sponsor
    end of 1:1-Block address materialSupport
    start of 1:1-Block address contact materialSupport
    •   [---]*
    •   [---]*
    •   [---]*
    •   [---]*
    end of 1:1-Block address contact materialSupport
end of 1:n-Block material support
start of 1:1-Block state

Status

  •   Recruiting ongoing
  •   [---]*
end of 1:1-Block state
start of 1:n-Block publications

Trial Publications, Results and other Documents

end of 1:n-Block publications
The parameters in ClinicalTrials.gov and DRKS are not identical. Therefore the data import from ClinicalTrials.gov 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.