Suppression of Ovarian Function and Either Tamoxifen or Exemestane With or Without Chemotherapy in Treating Premenopausal Women With Resected Breast Cancer

Breast Cancer Clinical Trial

— PERCHE  

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00066807
• Other study ID #: CDR0000318832
• Secondary ID: IBCSG 26-02BIG 4
• Status: Terminated
• Phase: Phase 3
• First received: August 6, 2003
• Last updated: April 28, 2015
• Start date: August 2003
• Est. completion date: September 2014

Study information

• Verified date: April 2015
• Source: International Breast Cancer Study Group
• Contact: n/a
• Is FDA regulated: No
• Health authority: Australia: Department of Health and Ageing Therapeutic Goods AdministrationGermany: Federal Institute for Drugs and Medical DevicesHungary: National Institute of PharmacyItaly: The Italian Medicines AgencySwitzerland: SwissmedicUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Estrogen can stimulate the growth of breast tumor cells. Suppression of ovarian function combined with hormone therapy may fight breast cancer by reducing the production of estrogen. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. It is not yet known whether suppression of ovarian function and hormone therapy are more effective with or without chemotherapy in treating breast cancer.

PURPOSE: This randomized phase III trial is studying how well giving ovarian-function suppression together with hormone therapy and chemotherapy works compared to ovarian-function suppression and hormone therapy alone in treating premenopausal women with resected breast cancer.

Description:

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.

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). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive ovarian function suppression comprising triptorelin intramuscularly on day 1 every 28 days for 5 years, oophorectomy, or ovarian irradiation. Beginning when ovarian function has been suppressed, patients also receive oral tamoxifen or exemestane once daily for 5 years in the absence of disease progression or unacceptable toxicity.

• Arm II: Patients receive ovarian function suppression as in arm I and concurrent chemotherapy for at least 2 months (if an anthracycline is included) or at least 4 months (if no anthracycline is included). Beginning after the completion of chemotherapy or when ovarian function has been suppressed, patients also receive oral tamoxifen or exemestane as in arm I.

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.

PROJECTED ACCRUAL: A total of 1,750 patients will be accrued for this study within 7 years.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 29
• Est. completion date: September 2014
• Est. primary completion date: September 2014
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 65 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Drug:
• chemotherapy
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.
• exemestane
Exemestane (Aromasin®) 25 mg orally daily, preferably after food, until 5 years from date of randomization, unless relapse or intolerance should occur earlier.
• tamoxifen
Tamoxifen 20 mg orally daily until 5 years from date of randomization, unless relapse or intolerance should occur earlier.
• triptorelin
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.

Procedure:
• oophorectomy
Bilateral surgical oophorectomy via laparotomy or laparoscopy.

Radiation:
• radiation therapy
Radiation therapy to the conserved breast is required. Radiation therapy to the chest wall following mastectomy is optional (if given, it may also include nodal fields).

Locations

Country	Name	City	State
Hungary	National Institute of Oncology	Budapest
Italy	Centro di Riferimento Oncologico - Aviano	Aviano
Italy	European Institute of Oncology	Milan
Switzerland	Kantonsspital Graubuenden	Chur
Switzerland	Centre Hospitalier Universitaire Vaudois	Lausanne
Switzerland	Kantonsspital - St. Gallen	St. Gallen

Sponsors (3)

Lead Sponsor	Collaborator
International Breast Cancer Study Group	Breast International Group, National Cancer Institute (NCI)

Countries where clinical trial is conducted

Hungary,  Italy,  Switzerland, 

References & Publications (1)

Francis P, Fleming G, Nasi ML, et al.: Tailored treatment investigations for premenopausal women with endocrine responsive (ER+ and/or PGR+) breast cancer: the SOFT, TEXT, and PERCHE trials. [Abstract] The Breast 12 (Suppl 1): A-P104, S44, 2003.

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Disease-free Survival		For first time at a median follow up approximately 5 years	No
Secondary	Overall survival		For first time at a median follow up approximately 5 years	No
Secondary	Systemic Disease-free Survival		For first time at a median follow up approximately 5 years	No
Secondary	Sites of First Treatment Failure		For first time at a median follow up approximately 5 years	No