Premenopausal Endocrine Responsive Chemotherapy Trial

Study Overview
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Brief Summary
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The PERCHE trial evaluated the worth of adding adjuvant chemotherapy for premenopausal women with steroid hormone receptor positive early invasive breast cancer who receive ovarian function suppression plus either tamoxifen or exemestane for five years. The use of chemotherapy was determined by randomization. The method of ovarian function suppression (GnRH analogue for five years, surgical oophorectomy or ovarian irradiation) and the choice of tamoxifen or exemestane were determined by the investigator or by randomization in the IBCSG 25-02 TEXT trial [recommended option]. The trial was terminated early due to poor accrual.

Detailed Description
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OBJECTIVES: Compare ovarian function suppression and tamoxifen or exemestane with vs without adjuvant chemotherapy in premenopausal women with endocrine-responsive resected breast cancer. Compare the disease-free and overall survival of patients treated with these regimens. Compare sites of first treatment failure in patients treated with these regimens. Compare the incidence of second nonbreast malignancies in patients treated with these regimens. Compare the quality of life, including late side effects of early menopause, of patients treated with these regimens. PLANNED OUTLINE: This is a randomized, multicenter study. Patients are stratified according to participating center, number of positive axillary and/or internal mammary lymph nodes (0 vs 1 or more), method of ovarian function suppression (triptorelin vs oophorectomy vs ovarian irradiation), chemotherapy if randomized to arm II (not containing vs containing an anthracycline or taxane), and endocrine agent (tamoxifen vs exemestane vs selected by subsequent randomization in the TEXT trial). Treatment duration is five years. Quality of life is assessed at baseline, every 6 months for 2 years, and then annually for 4 years. Patients are followed every 3 months for 1 year, every 6 months for 5 years, and then annually thereafter. NOTE: Trial was terminated early due to poor accrual.

Official Title
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A Phase III Trial Evaluating the Role of Chemotherapy as Adjuvant Therapy for Premenopausal Women With Endocrine Responsive Breast Cancer Who Receive Endocrine Therapy

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: chemotherapy
* Drug: exemestane
* Drug: tamoxifen
* Drug: triptorelin
* Procedure: oophorectomy
* Procedure: ovarian irradiation


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed breast cancer confined to the breast and axillary nodes No distant metastatic disease Tumor detected in the internal mammary chain by sentinel node procedure allowed Must have undergone 1 of the following procedures for primary breast cancer within the past 12 weeks and have no known clinical residual locoregional disease: Total mastectomy with or without adjuvant radiotherapy Breast-conserving surgery (e.g., lumpectomy, quadrantectomy, or partial mastectomy with margins clear* of invasive cancer and ductal carcinoma in situ) followed by radiotherapy NOTE: *If all other margins are clear, a positive posterior (deep) margin is permitted, provided the excision was performed down to the pectoral fascia and all tumor has been removed OR a positive anterior (superficial; abutting skin) margin is allowed provided all tumor was removed Prior axillary lymph node dissection or negative axillary sentinel node biopsy required Patients with microscopically positive axillary sentinel nodes allowed provided they were evaluated on a clinical trial evaluating microscopically positive lymph nodes No locally advanced, inoperable breast cancer, including any of the following characteristics: Inflammatory breast cancer Supraclavicular node involvement Enlarged internal mammary nodes (unless pathologically negative) No prior ipsilateral or contralateral invasive breast cancer Histologically diagnosed synchronous bilateral invasive breast cancer within the past 2 months allowed if the bilateral disease meets all other eligibility criteria Hormone receptor status: Estrogen receptor and/or progesterone receptor positive in each tumor At least 10% of tumor cells positive by immunohistochemistry PATIENT CHARACTERISTICS: Age Premenopausal Sex Female Menopausal status Premenopausal Estradiol in the premenopausal range after surgery Performance status Not specified Life expectancy Not specified Hematopoietic Not specified Hepatic No systemic hepatic disease that would preclude prolonged follow-up Renal No systemic renal disease that would preclude prolonged follow-up Cardiovascular No prior deep venous thrombosis and/or embolism unless patient is medically suitable No systemic cardiovascular disease that would preclude prolonged follow-up Pulmonary No systemic pulmonary disease that would preclude prolonged follow-up Other Not pregnant or nursing Fertile patients must use effective nonhormonal contraception No other prior or concurrent invasive malignancy except adequately treated basal cell or squamous cell skin cancer, nonbreast carcinoma in situ without invasion, contralateral or ipsilateral carcinoma in situ of the breast No prior or concurrent nonbreast invasive malignancy within the past 5 years that is nonrecurrent including any of the following: Stage I papillary thyroid cancer Stage Ia carcinoma of the cervix Stage Ia or b endometrioid endometrial cancer Borderline or stage I ovarian cancer No other nonmalignant systemic disease that would preclude prolonged follow-up No history of noncompliance with medical regimens No psychiatric, addictive, or other disorder that would preclude study compliance or giving informed consent PRIOR CONCURRENT THERAPY: Biologic therapy Not specified Chemotherapy No prior neoadjuvant or adjuvant chemotherapy Neoadjuvant or adjuvant trastuzumab (Herceptin®) allowed Endocrine therapy No prior neoadjuvant or adjuvant endocrine therapy after breast cancer diagnosis No prior tamoxifen or other selective estrogen-receptor modulator (e.g., raloxifene) within 1 year before the breast cancer diagnosis No other concurrent oral or transdermal hormonal therapy, including any of the following: Estrogen Progesterone Androgens Aromatase inhibitors Hormone replacement therapy Oral or other hormonal contraceptives, including implant and depot injections Raloxifene or other selective estrogen-receptor modulators Radiotherapy See Disease Characteristics No prior ovarian irradiation Surgery See Disease Characteristics No prior bilateral oophorectomy Other No other prior neoadjuvant therapy No other concurrent investigational agents No concurrent bisphosphonates unless bone density has been documented at least 1.5 standard deviations below the young adult normal mean or the patient is participating in a randomized clinical trial setting testing bisphosphonates in the adjuvant breast cancer setting

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: OFS plus T or E<br>Ovarian function suppression (OFS) by triptorelin for 5 years or surgical oophorectomy or ovarian irradiation PLUS tamoxifen (T) or exemestane (E) for 5 years. | Drug: exemestane<br>* Exemestane 25 mg orally daily for until 5 years from date of randomization, unless relapse or intolerance should occur earlier.<br>* Other names: Aromasin;Drug: tamoxifen<br>* Tamoxifen 20 mg orally daily until 5 years from date of randomization, unless relapse or intolerance should occur earlier.<br>* Other names: Nolvadex;Drug: triptorelin<br>* Triptorelin (GnRH analogue) 3.75 mg by intramuscular injection every 28 days for 5 years from randomization, unless relapse or intolerance should occur earlier or surgical oophorectomy or ovarian irradiation is subsequently performed.<br>* Other names: Trelstar Depot;Procedure: oophorectomy<br>* Bilateral surgical oophorectomy via laparotomy or laparoscopy.<br>Procedure: ovarian irradiation<br>* Bilateral ovarian irradiation.<br>|
| Experimental: Chemotherapy plus OFS plus T or E<br>Chemotherapy plus ovarian function suppression (OFS) by triptorelin for 5 years or surgical oophorectomy or ovarian irradiation PLUS tamoxifen (T) or exemestane (E) for 5 years. | Drug: chemotherapy<br>* Planned duration of chemotherapy: 2 months if an anthracycline is included (e.g., 4 cycles of EC or AC) or 4 months if no anthracycline is given (e.g., 6 cycles of CMF) is recommended. Unless medically contraindicated, an anthracycline-containing regimen using epirubicin should be given.<br>* Other names: Epirubicin Ebewe;Drug: exemestane<br>* Exemestane 25 mg orally daily for until 5 years from date of randomization, unless relapse or intolerance should occur earlier.<br>* Other names: Aromasin;Drug: tamoxifen<br>* Tamoxifen 20 mg orally daily until 5 years from date of randomization, unless relapse or intolerance should occur earlier.<br>* Other names: Nolvadex;Drug: triptorelin<br>* Triptorelin (GnRH analogue) 3.75 mg by intramuscular injection every 28 days for 5 years from randomization, unless relapse or intolerance should occur earlier or surgical oophorectomy or ovarian irradiation is subsequently performed.<br>* Other names: Trelstar Depot;Procedure: oophorectomy<br>* Bilateral surgical oophorectomy via laparotomy or laparoscopy.<br>Procedure: ovarian irradiation<br>* Bilateral ovarian irradiation.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease-free Survival |  | For first time at a median follow up approximately 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival |  | For first time at a median follow up approximately 5 years | 
| Systemic Disease-free Survival |  | For first time at a median follow up approximately 5 years | 
| Sites of First Treatment Failure |  | For first time at a median follow up approximately 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage IIIA breast cancer, stage I breast cancer, stage II breast cancer