Trial record 2 of 285 for:    "Breast cancer male"

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 (MALE)

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2012 by German Breast Group
Sponsor:
Collaborator:
Pfizer
Information provided by (Responsible Party):
German Breast Group
ClinicalTrials.gov Identifier:
NCT01638247
First received: July 9, 2012
Last updated: October 23, 2012
Last verified: October 2012
  Purpose

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.


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
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment

Resource links provided by NLM:


Further study details as provided by German Breast Group:

Primary Outcome Measures:
  • Estradiol blood concentation [ Time Frame: 3 months. ] [ Designated as safety issue: No ]
    To determine the estradiol suppression between the three treatment arms after three months.


Secondary Outcome Measures:
  • Estradiol blood concentration [ Time Frame: 6 months. ] [ Designated as safety issue: No ]
    To determine the estradiol suppression between the three treatment arms after six months.

  • Compliance [ Time Frame: 6 months. ] [ Designated as safety issue: Yes ]
    To compare the compliance in the three treatment arms.

  • Efficacy [ Time Frame: 6 months. ] [ Designated as safety issue: No ]
    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. ] [ Designated as safety issue: No ]
    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. ] [ Designated as safety issue: Yes ]

    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).


Estimated Enrollment: 48
Study Start Date: August 2012
Estimated Study Completion Date: March 2015
Estimated Primary Completion Date: March 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Tamoxifen
Tamoxifen alone (daily).
Drug: Tamoxifen
25 mg daily.
Experimental: Tamoxifen + 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 + 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.

  Eligibility

Ages Eligible for Study:   18 Years to 85 Years
Genders 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 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.

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).
  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

Contacts
Contact: Mathias Uhlig, Ph.D. +49-6102-7480 ext 414 mathias.uhlig@germanbreastgroup.de
Contact: Konstantin Reißmüller +49-6102-7480 ext 438 konstantin.reissmueller@germanbreastgroup.de

Locations
Germany
Klinikum Offenbach Recruiting
Offenbach, Hessen, Germany, 63069
Contact: Sibylle Loibl, MD    +49-6102-7480 ext 426    sibylle.loibl@germanbreastgroup.de   
Sub-Investigator: Sibylle Loibl, MD         
Sponsors and Collaborators
German Breast Group
Pfizer
Investigators
Principal Investigator: Sibylle Loibl, MD GBG Forschungs GmbH
  More Information

Additional Information:
No publications provided

Responsible Party: German Breast Group
ClinicalTrials.gov Identifier: NCT01638247     History of Changes
Other Study ID Numbers: GBG 54, 2009-015122-11
Study First Received: July 9, 2012
Last Updated: October 23, 2012
Health Authority: Bundesinstitut für Arzneimittel und Medizinprodukte Bonn: Deutschland
Germany: Federal Institute for Drugs and Medical Devices

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

Additional relevant MeSH terms:
Breast Neoplasms
Breast Neoplasms, Male
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Tamoxifen
Exemestane
Aromatase Inhibitors
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Selective Estrogen Receptor Modulators
Estrogen Receptor Modulators
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Bone Density Conservation Agents
Estrogen Antagonists
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 24, 2014