Suppression of Ovarian Function and Either Tamoxifen or Exemestane With or Without Chemotherapy in Treating Premenopausal Women With Resected Breast Cancer (PERCHE)
This study is ongoing, but not recruiting participants.
Sponsor:
International Breast Cancer Study Group
Collaborators:
Breast International Group
Information provided by (Responsible Party):
International Breast Cancer Study Group
ClinicalTrials.gov Identifier:
NCT00066807
First received: August 6, 2003
Last updated: July 20, 2012
Last verified: July 2012
- Full Text View
- Tabular View
- No Study Results Posted
- Disclaimer
- How to Read a Study Record
Purpose
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.
| Condition | Intervention | Phase |
|---|---|---|
|
Breast Cancer |
Drug: chemotherapy Drug: exemestane Drug: tamoxifen citrate Drug: triptorelin Procedure: oophorectomy Radiation: radiation therapy |
Phase 3 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment |
| 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 |
Resource links provided by NLM:
Further study details as provided by International Breast Cancer Study Group:
Primary Outcome Measures:
- Relapse (i.e., local, regional, or distant) [ Time Frame: 7 years after inclusion of last patient ] [ Designated as safety issue: No ]
- Contralateral breast cancer [ Time Frame: 7 years after inclusion of last patient ] [ Designated as safety issue: No ]
- Second (nonbreast) primary tumor [ Time Frame: 7 years after inclusion of last patient ] [ Designated as safety issue: No ]
- Death [ Time Frame: 7 years after inclusion of last patient ] [ Designated as safety issue: No ]
Secondary Outcome Measures:
- Overall survival [ Time Frame: 7 years after inclusion of last patient ] [ Designated as safety issue: No ]
| Enrollment: | 29 |
| Study Start Date: | August 2003 |
| Estimated Primary Completion Date: | May 2013 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: OFS plus tamoxifen or exemestane for 5 years
Patients will undergo ovarian function suppression (by treatment with triptorelin, bilateral surgical oophorectomy or bilateral ovarian irradiation), and will be treated with tamoxifen or exemestane for 5 years after randomisation.
|
Drug: exemestane
Exemestane (Aromasin®) 25 mg orally daily, preferably after food, until 5 years from date of randomization, unless relapse or intolerance should occur earlier.
Drug: tamoxifen citrate
Tamoxifen 20 mg orally daily until 5 years from date of randomization, unless relapse or intolerance should occur earlier.
Drug: 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).
|
|
Experimental: Chemotherapy plus OFS plus tamoxifen or exemestane for 5 years
Patients will receive chemotherapy and undergo ovarian function suppression (by treatment with triptorelin, bilateral surgical oophorectomy or bilateral ovarian irradiation) after randomisation, and will be treated with tamoxifen or exemestane for 5 years after completion of chemotherapy.
|
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.
Drug: exemestane
Exemestane (Aromasin®) 25 mg orally daily, preferably after food, until 5 years from date of randomization, unless relapse or intolerance should occur earlier.
Drug: tamoxifen citrate
Tamoxifen 20 mg orally daily until 5 years from date of randomization, unless relapse or intolerance should occur earlier.
Drug: 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).
|
Detailed 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.
Eligibility| Genders Eligible for Study: | Female |
| Accepts Healthy Volunteers: | No |
Criteria
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
Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00066807
Locations
| Hungary | |
| National Institute of Oncology | |
| Budapest, Hungary, 1122 | |
| Italy | |
| Centro di Riferimento Oncologico - Aviano | |
| Aviano, Italy, 33081 | |
| European Institute of Oncology | |
| Milan, Italy, 20141 | |
| Switzerland | |
| Kantonsspital Graubuenden | |
| Chur, Switzerland, CH-7000 | |
| Centre Hospitalier Universitaire Vaudois | |
| Lausanne, Switzerland, 1011 | |
| Kantonsspital - St. Gallen | |
| St. Gallen, Switzerland, CH-9007 | |
Sponsors and Collaborators
International Breast Cancer Study Group
Breast International Group
Investigators
| Study Chair: | Rosalba Torrisi, MD | European Institute of Oncology |
More Information
Additional Information:
Publications:
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.
| Responsible Party: | International Breast Cancer Study Group |
| ClinicalTrials.gov Identifier: | NCT00066807 History of Changes |
| Other Study ID Numbers: | CDR0000318832, IBCSG-26-02, BIG-4-02, NABCI-IBCSG-26-02, EU-20401, 2005-002626-59 |
| Study First Received: | August 6, 2003 |
| Last Updated: | July 20, 2012 |
| Health Authority: | Australia: Department of Health and Ageing Therapeutic Goods Administration Germany: Federal Institute for Drugs and Medical Devices Hungary: National Institute of Pharmacy Italy: The Italian Medicines Agency Switzerland: Swissmedic United States: Federal Government |
Keywords provided by International Breast Cancer Study Group:
|
stage IIIA breast cancer stage I breast cancer stage II breast cancer |
Additional relevant MeSH terms:
|
Breast Neoplasms Neoplasms by Site Neoplasms Breast Diseases Skin Diseases Tamoxifen Triptorelin Exemestane 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 Aromatase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Luteolytic Agents Contraceptive Agents, Female Contraceptive Agents Reproductive Control Agents |
ClinicalTrials.gov processed this record on May 16, 2013