Adjuvant Toremifene With or Without Goserrelin in Premenopausal Women With Stage I-IIIA, Hormonal Receptor Positive Breast Cancer Accompanied With or Without Chemotherapy Induced Amenorrhoea

Study Overview
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Brief Summary
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Compare the potential benefits of adjuvant toremifene with or without goserelin in premenopausal women with stage I-IIIA, hormonal receptor positive breast cancer accompanied with or without chemotherapy induced amenorrhoea.

Detailed Description
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This is a single center, randomized, controlled study. Patients undergo surgical resection with standard Doxorubicin/Cyclophosphamide Followed by Docetaxel (AC-T). Chemotherapy begins within 4 weeks after surgery for patients randomized to arm I-IV. Arm I: patients who didn't have CIA receive oral toremifene daily. Treatment continues for 5 years in the absence of disease progression or unacceptable toxicity. Arm II: patients who had CIA receive toremifene as in arm I. Arm III: patients without CIA receive oral toremifene and goserelin for ovarian function suppression. Arm IV: patients with CIA receive oral toremifene and goserelin for ovarian function suppression. Patients are followed every 6 months for 5 years and annually thereafter.

Official Title
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Study of Adjuvant Toremifene With or Without Goserrelin in Premenopausal Women With Stage I-IIIA, Hormonal Receptor Positive Breast Cancer Accompanied With or Without Chemotherapy Induced Amenorrhoea

Conditions
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Breast Cancer, Chemotherapy Induced Amenorrhea, Ovarian Function Suppression

Intervention / Treatment
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* Drug: Goserelin
* Drug: Toremifene


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written informed consent must be obtained and documented according to the local regulatory requirements prior to beginning specific protocol procedures Age of at least 18 and at most 45 years Spontaneous and regular menstrual periods before study entry with FSH below 15 mlU/ml in follicular phase Histologically confirmed primary breast cancer with the need for anthracycline-based chemotherapy Steroid receptor (estrogen and progesterone) positive tumor (diagnosis according to hospital standard-procedures) No clinical evidence of local recurrence or distant metastases. Complete staging work-up within 3 months prior to registration. All patients must have (bilateral) mammography or breast MRI, chest X-ray; other tests may be performed as clinically indicated Karnofsky-Index >80% Life expectancy of at least 10 years, disregarding the diagnosis of cancer Adequate organ function including normal red and white blood count, platelets, serum creatinine, bilirubin, and transaminases within normal range of the institution Patients underwent standard Doxorubicin/Cyclophosphamide Followed by Docetaxel (AC-T) Patients must be available for and compliant to treatment and follow-up. Patients registered on this trial must be treated and followed up at the participating center. Exclusion Criteria: Known hypersensitivity reaction to the investigational compounds or incorporated substances Prior cytotoxic treatment for any reason Suspected (primary or secondary) ovarian insufficiency Pregnant or lactating patients. Patients of childbearing potential must have a negative pregnancy test (urine or serum) within 14 days prior to registration and must implement adequate non-hormonal contraceptive measures during study treatment; prior use of hormonal contraceptives has to be discontinued before first Goserelin injection Other serious illness or medical condition that may interfere with the understanding and giving of informed consent and the conduct of the study Prior or concomitant secondary malignancy (except non-melanomatous skin cancer or carcinoma in situ of the uterine cervix) Concurrent treatment with other experimental drugs or any other anti-cancer therapy Concurrent treatment with sex hormones. Prior treatment must be stopped before study entry

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I<br>Patients who didn't have CIA receive oral toremifene daily. Treatment continues for 5 years in the absence of disease progression or unacceptable toxicity | Drug: Toremifene<br> <br> |
| Experimental: Arm II<br>Patients who had CIA receive toremifene as in arm I | Drug: Toremifene<br> <br> |
| Experimental: Arm III<br>Patients without CIA receive oral toremifene and goserelin for ovarian function suppression | Drug: Goserelin<br> <br> * Other names: Zoladex;|
| Experimental: Arm IV<br>Patients with CIA receive oral toremifene and goserelin for ovarian function suppression. | Drug: Goserelin<br> <br> * Other names: Zoladex;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease free survival |  | up to 120 months | 
| Overall Survival |  | up to 120 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quality of life |  | up to 120 months | 
| Bone mineral density loss | measured by dual energy X-ray absorptiometry scans at every 12 months and by serum biomarkers | up to 120 months | 
| Hormone levels |  | up to 120 months | 
| Incidence of pregnancy |  | up to 120 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Goserelin, Breast cancer, Chemotherapy induced amenorrhea