Male Breast CancerPhase 3MALENCT01638247
Tamoxifen +/- GnRH Analogue vs Aromatase Inhibitor + GnRH Analogue in Male Breast Cancer Patients
A Phase 3 study testing Tamoxifen, Tamoxifen and GnRH analogue and Exemestane and GnRH analogue in people with Male Breast Cancer, run by GBG Forschungs GmbH at 1 site in Germany.
Trial summary
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). Read more about this study
- Who is it for?
- Ages 18 to 85 years, men only
- Conditions the study is for
- Male Breast Cancer
- What is being tested?
- Tamoxifen, Tamoxifen and GnRH analogue and Exemestane and GnRH analogue
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 56 participants
- Where
- 1 siteGermany
- Study dates
- Aug 2012to May 2018
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 85 years
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Written informed consent for all study procedures.
- Complete baseline documentation sent to GBG Forschungs GmbH.
- Male patients.
- Age ≥ 18 years.
- Karnofsky-Index ≥ 60%.
- Histologically confirmed unilateral or bilateral carcinoma or of the breast at primary diagnosis (enrolment possible in neoadjuvant, adjuvant and metastatic situation).
Show all 23Show fewer
- 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.
Who cannot join
- Female patients.
- Prior endocrine therapy of breast carcinoma.
- Known or suspected hypersensitivity reaction to the compounds or incorporated substances.
- No indication for endocrine treatment.
- Life expectancy of less than six months.
- International Prostate Symptom Score (IPSS) > 17.
Show all 14Show fewer
- Current diagnosis of a Prostate carcinoma.
- 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.
- Concurrent neuronal or cardiac disease, poorly controlled arterial hypertension.
- Previous thromboembolic event within the last five years (except from thromboembolic events correlated to implanted devices (e.g. port thrombosis)
- Currently active hepatitis.
- Disease significantly affecting gastrointestinal function, e.g. malabsorption syndrome, resection of the stomach or small bowel.
- 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.
- Patients who are not able to give informed consent as defined according to AMG.
Trial locations and contacts
1 site in 1 country.
About this study
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
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).
Read the 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.
- Conditions
- Male Breast Cancer
- Being tested
- Tamoxifen, Tamoxifen and GnRH analogue, Exemestane and GnRH analogue
- Keywords
- Male breast cancer, neoadjuvant, adjuvant or metastatic situation, anti-hormonal therapy
- Medical subject headings
- Breast Neoplasms, Male
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TamoxifenDrug
25 mg daily.
Tamoxifen and GnRH analogueDrug
Also called TRENATONE, ZOLADEX
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).
Exemestane and GnRH analogueDrug
Also called AROMASIN, TRENATONE, ZOLADEX.
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).
| Study group | Role | What they receive |
|---|---|---|
| Tamoxifen | Active comparator | Tamoxifen alone (daily). Receives: Drug: Tamoxifen |
| Tamoxifen and GnRH analogue | Experimental | Tamoxifen (daily) + GnRH analogue (at randomisation and after three months). Receives: Drug: Tamoxifen and GnRH analogue |
| Exemestane and GnRH analogue | Experimental | Exemestane (daily) + GnRH analogue (at randomisation and after three months). Receives: Drug: Exemestane and GnRH analogue |
What is being measured
The primary outcome is the main question the study is designed to answer.
Estradiol blood concentation
To determine the estradiol suppression between the three treatment arms after three months.
Measured: 3 months.
Secondary outcomes (5)
Estradiol blood concentration
To determine the estradiol suppression between the three treatment arms after six months.
Measured: 6 months.
Compliance
To compare the compliance in the three treatment arms.
Measured: 6 months.
Efficacy
To compare the efficacy in terms of overall response (for neoadjuvant and metastatic patients) in the three treatment arms.
Measured: 6 months.
Efficacy perameters
To compare testosterone, dihydrotestosterone (DHT), SHBG, FSH, LH, osteocalcin and CTX in the three treatments arms.
Measured: 6 months.
Safety and side effect parameters
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).
Measured: 6 months.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jul 2012 (estimated)
- Study startAug 2012
- Primary completionMay 2018
- Study completionMay 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Male Breast CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 56 participants (actual)
Sponsor and investigators
- Lead sponsor
- GBG Forschungs GmbH
- Sponsor type
- University, hospital or other
- Collaborators
- Pfizer
- Responsible party
- Sponsor
- Investigators
- Mattea Reinisch, MD, Principal investigator, Kliniken Essen-Mitte
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01638247
- Sponsor's protocol ID
- GBG 54
- Other IDs
- 2009-015122-11, 2009
- Acronym
- MALE
- Status last verified
- Sep 2018
- First submitted
- 9 Jul 2012
- Last updated
- 19 Sep 2018
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Reinisch M, Seiler S, Hauzenberger T, Kamischke A, Schmatloch S, Strittmatter HJ, Zahm DM, Thode C, Furlanetto J, Strik D, Mobus V, Reimer T, Sinn BV, Stickeler E, Marme F, Janni W, Schmidt M, Rudlowski C, Untch M, Nekljudova V, Loibl S. Efficacy of Endocrine Therapy for the Treatment of Breast Cancer in Men: Results from the MALE Phase 2 Randomized Clinical Trial. JAMA Oncol. 2021 Apr 1;7(4):565-572. doi: 10.1001/jamaoncol.2020.7442.
PubMed 33538790
Study at a glance
From the registry record, last updated by the sponsor on 19 Sep 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01638247
- Acronym / sponsor ID
- MALE / GBG 54
- Conditions
- Male Breast Cancer
- Keywords
- Male breast cancer, neoadjuvant, adjuvant or metastatic situation, anti-hormonal therapy
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 56 participants (actual)
- Lead sponsor
- GBG Forschungs GmbHUniversity, hospital or other
- Collaborators
- Pfizer
- Study start
- Aug 2012 (actual)
- Primary completion
- May 2018 (actual)
- Study completion
- May 2018 (actual)
- First posted
- 11 Jul 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Tamoxifen | Active comparator | Drug: TamoxifenTamoxifen alone (daily). |
| Tamoxifen and GnRH analogue | Experimental | Drug: Tamoxifen and GnRH analogueTamoxifen (daily) + GnRH analogue (at randomisation and after three months). |
| Exemestane and GnRH analogue | Experimental | Drug: Exemestane and GnRH analogueExemestane (daily) + GnRH analogue (at randomisation and after three months). |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (23 listed)
- Written informed consent for all study procedures.
- Complete baseline documentation sent to GBG Forschungs GmbH.
- Male patients.
- Age ≥ 18 years.
- Karnofsky-Index ≥ 60%.
Key exclusion criteria (14 listed)
- Female patients.
- Prior endocrine therapy of breast carcinoma.
- Known or suspected hypersensitivity reaction to the compounds or incorporated substances.
- No indication for endocrine treatment.
- Life expectancy of less than six months.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Tamoxifen25 mg daily. | Drug | Tamoxifen |
| Tamoxifen and GnRH analogueAlso: TRENATONE, ZOLADEX25 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). | Drug | Tamoxifen and GnRH analogue |
| Exemestane and GnRH analogueAlso: AROMASIN, TRENATONE, ZOLADEX.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). | Drug | Exemestane and GnRH analogue |
Primary outcome
Estradiol blood concentation
Time frame: 3 months.
To determine the estradiol suppression between the three treatment arms after three months.
5 secondary outcomes
Estradiol blood concentration
Time frame: 6 months.
Compliance
Time frame: 6 months.
Efficacy
Time frame: 6 months.
Efficacy perameters
Time frame: 6 months.
Safety and side effect parameters
Time frame: 6 months.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Sep 2018.
- Derived from this study: PubMed 33538790Reinisch M, Seiler S, Hauzenberger T, Kamischke A, Schmatloch S, Strittmatter HJ, Zahm DM, Thode C, Furlanetto J, Strik D, Mobus V, Reimer T, Sinn BV, Stickeler E, Marme F, Janni W, Schmidt M, Rudlowski C, Untch M, Nekljudova V, Loibl S. Efficacy of Endocrine Therapy for the Treatment of Breast Cancer in Men: Results from the MALE Phase 2 Randomized Clinical Trial. JAMA Oncol. 2021 Apr 1;7(4):565-572. doi: 10.1001/jamaoncol.2020.7442.
- Sponsor study homepageLink provided by the sponsor.
Related trials for Male Breast Cancer
Active, not recruiting
Streamlined Geriatric and Oncological Evaluation Based On IC Technology
Breast Cancer, Comorbidities and Coexisting Conditions
Enrolling by invitationObservational study
Natural History Study of Early Life Exposures in Agriculture (ELEA)
Prostate Cancer, Leukemia
Active, not recruitingPhase 1/2
Study of Oral MRT-2359 in Selected Cancer Patients
NSCLC, SCLC
Recruiting
The Vanguard Study: Testing a New Way to Screen for Cancer
Bladder Carcinoma, Breast Carcinoma
Active, not recruitingPhase 1
A Phase 1 Study of XL309 (ISM3091) Alone and in Combination in Participants With Advanced Solid Tumors
Advanced Solid Tumor
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mattea Reinisch, MD principal investigator
Kliniken Essen-Mitte
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Tamoxifen, Tamoxifen and GnRH analogue and Exemestane and GnRH analogue in people with Male Breast Cancer, run by GBG Forschungs GmbH at 1 site in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 23 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 Sep 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Estradiol blood concentation (time frame: 3 months.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01638247, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Sep 2018.