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Tamoxifen +/- GnRH Analogue vs Aromatase Inhibitor + GnRH Analogue in Male Breast Cancer Patients (MALE)

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Pfizer
Information provided by (Responsible Party):
German Breast Group
ClinicalTrials.gov Identifier:
NCT01638247
First received: July 9, 2012
Last updated: August 25, 2017
Last verified: July 2017
  Purpose
A prospective, randomised multi-centre phase II study evaluating the adjuvant, neoadjuvant or palliative treatment with tamoxifen +/- GnRH analogue versus aromatase inhibitor + GnRH analogue in male breast cancer patients (MALE).

Condition Intervention Phase
Male Breast Cancer Drug: Tamoxifen Drug: Tamoxifen and GnRH analogue Drug: Exemestane and GnRH analogue Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (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

Resource links provided by NLM:


Further study details as provided by German Breast Group:

Primary Outcome Measures:
  • Estradiol blood concentation [ Time Frame: 3 months. ]
    To determine the estradiol suppression between the three treatment arms after three months.


Secondary Outcome Measures:
  • 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).


Enrollment: 56
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)
Arms Assigned Interventions
Active Comparator: Tamoxifen
Tamoxifen alone (daily).
Drug: Tamoxifen
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:

  • Goserelin (10.8 mg s.c. after randomisation and after three months) or
  • Leuprorelin (11.25 mg s.c. after randomisation and after three months).
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:

  • Goserelin (10.8 mg s.c. after randomisation and after three months) or
  • Leuprorelin (11.25 mg s.c. after randomisation and after three months).
Other Name: AROMASIN, TRENATONE, ZOLADEX.

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years to 85 Years   (Adult, Senior)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

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 of the breast at primary diagnosis (enrolment possible in neoadjuvant, adjuvant and metastatic situation).

7: No target lesion necessary for metastatic situation 8. Positive hormone receptor status (e.g. ER and/or PR-receptor positive). 9. Completed staging prior randomisation ( within 8 weeks after diagnose or last therapy (operation, chemotherapy or radiation), 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.

10. 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.

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

12. Laboratory requirements (≤ 14 days before therapy start): Hematology

  • Hemoglobin ≥ 9 g/dL,
  • Leukocytes 4 - 10 x1000/µL,
  • Thrombocytes 150 - 400 x1000/µL. Hepatic function
  • ASAT (SGOT) or ALAT (SGPT) ≤ 2x UNL,
  • Total bilirubin ≤ 2x UNL. Renal function
  • Serum creatinine ≤ 1.5x UNL,
  • Creatinine clearance > 30 mL/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. 13. Two serum samples (5 mL) centrally made available. 14. Paraffin tumor tissue block and full blood sample centrally made available (except when the patient does not agree to central biomaterial collection).

    15. The patient must be accessible for treatment. Patients can simultaneously be registered in the register study of the University Hospital of Magdeburg.

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. Current diagnosis of a Prostate carcinoma.
  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 (except from thromboembolic events correlated to implanted devices (e.g. port thrombosis)
  11. Currently active hepatitis.
  12. Disease significantly affecting gastrointestinal function, e.g. malabsorption syndrome, resection of the stomach or small bowel.
  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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01638247

Locations
Germany
Kliniken Essen-Mitte
Essen, Nordrhein-Westfalen, Germany, 45136
Sponsors and Collaborators
German Breast Group
Pfizer
Investigators
Principal Investigator: Mattea Reinisch, MD Kliniken Essen-Mitte
  More Information

Responsible Party: German Breast Group
ClinicalTrials.gov Identifier: NCT01638247     History of Changes
Other Study ID Numbers: GBG 54
2009-015122-11 ( EudraCT Number )
Study First Received: July 9, 2012
Last Updated: August 25, 2017

Keywords provided by German Breast Group:
Male breast cancer
neoadjuvant, adjuvant or metastatic situation
anti-hormonal therapy

Additional relevant MeSH terms:
Breast Neoplasms, Male
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Tamoxifen
Exemestane
Goserelin
Prolactin Release-Inhibiting Factors
Aromatase Inhibitors
Estrogen Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Selective Estrogen Receptor Modulators
Estrogen Receptor Modulators
Bone Density Conservation Agents
Hormones
Steroid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 21, 2017