Clinical trial NCT00066807: Premenopausal Endocrine Responsive Chemotherapy Trial
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Breast Cancer
Keywords: stage IIIA breast cancer
stage I breast cancer
stage II breast cancer
Lead sponsor: ETOP IBCSG Partners Foundation
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
name: Breast International Group
First posted: 2003-08-07
Enrollment: 29
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility 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

Primary outcomes:
measure: Disease-free Survival
timeFrame: For first time at a median follow up approximately 5 years
Secondary outcomes:
measure: Overall Survival
timeFrame: For first time at a median follow up approximately 5 years
measure: Systemic Disease-free Survival
timeFrame: For first time at a median follow up approximately 5 years
measure: Sites of First Treatment Failure
timeFrame: For first time at a median follow up approximately 5 years
Other outcomes:
Locations:
city: Budapest
country: Hungary
facility: National Institute of Oncology
city: Aviano
country: Italy
facility: Centro di Riferimento Oncologico - Aviano
city: Milan
country: Italy
facility: European Institute of Oncology
city: Chur
country: Switzerland
facility: Kantonsspital Graubuenden
city: Lausanne
country: Switzerland
facility: Centre Hospitalier Universitaire Vaudois
city: St. Gallen
country: Switzerland
facility: Kantonsspital - St. Gallen
Study officials:
affiliation: Breast International Group, European Institute of Oncology, Milano, Italy
name: Rosalba Torrisi, MD
role: STUDY_CHAIR
affiliation: North American Intergroup, Mayo Clinic Jacksonville, Jacksonville, USA
name: Edith A. Perez, MD
role: STUDY_CHAIR
References:
citation: 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.