Suppression of Ovarian Funktion Trial (SOFT)

Phase 1

Conditions: MedDRA version: 19.0Level: PTClassification code 10057654Term: Breast cancer femaleSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Therapeutic area: Diseases [C] - Cancer [C04]
Histologically proven, resected breast cancer with ER and/or PgR positive tumors

Registration Number: EUCTR2004-000166-13-DE

Lead Sponsor: GBG Forschungs GmbH

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: Female

Target Recruitment: 3000

Inclusion Criteria

Premenopausal women [estradiol (E2) in the premenopausal range] who meet the following criteria:
Patients who did not receive chemotherapy should be randomized within 12 weeks after definitive surgery. Such patients should have estradiol (E2) in the premeno pausal range following surgery; the only patients who do not require testing of estradiol (E2) to confirm premenopausal status are those who have been menstruating regularly during the 6 months prior to randomization and have not used any form of hormonal contraception or any other hormonal treatments during the 6 months prior to randomization.
Patients who received prior adjuvant and/or neoadjuvant chemotherapy should be randomized after completing chemotherapy and within 8 months of the final dose of chemotherapy as soon as premenopausal status is confirmed; all such patients should have premenopausal status confirmed by an estradiol (E2) in the premeno-pausal range between 2 weeks and 8 months after completing chemotherapy. Adjuvant trastuzumab (Herceptin ®) is allowable, and is not considered to be chemo-therapy for eligibility timing determination.
Patients with temporary chemotherapy-induced amenorrhea who regain premeno- pausal status within eight months of the final dose of chemotherapy are eligible. [Please note that some patients taking tamoxifen or aromatase inhibitors, even without evidence of menses, may have ovarian function recovery following chemo-therapy and resume estradiol secretion.] Premenopausal levels of serum estradiol may persist after chemotherapy-induced amenorrhea despite prolonged amenorrhea [34]. Therefore in patients wishing to participate in the study, with ostmenopausal hormone levels shortly after chemotherapy, it is recommended to recheck their estradiol level at a later timepoint within 8 months of completing chemotherapy, even in the absence of return of menses.

Histologically proven, resected breast cancer. Pathology material should be available for submission for central review as part of the quality control measures for this protocol.

Patients must have hormone receptor positive tumors. If there is more than one breast tumor, each tumor must be hormone receptor positive. Hormone receptors must be determined using immunohistochemistry. ER and/or PgR must be greater than or equal to 10% of the tumor cells positive by immunohistochemical evaluation.

The tumor must be confined to the breast and axillary nodes without detected metastases elsewhere, with the exception of tumor detected in internal mammary chain nodes by sentinel node procedure. Patients who received neoadjuvant therapy must have had operable disease prior to neoadjuvant treatment to be eligible. Patients who had a pathological evaluation with tru cut or core biopsy of invasive breast cancer prior to neoadjuvant therapy and were found to have no invasive tumor in the pathological specimen from definitive surgery are eligible.

Patients must have had proper surgery for primary breast cancer with no known clinical residual loco-regional disease:
A total mastectomy. Radiotherapy is optional after mastectomy.
OR
A breast-conserving procedure (lumpectomy, quadrantectomy or partial mastectomy with margins clear of invasive cancer and DCIS). The local pathologist must document negative margins of resection in the pathology report. If all other margins are clear, a positive posterior (deep) margin is permitted, provided the surgeon documents that the excision was perfo

Exclusion Criteria

Patients who are postmenopausal (i.e., do not have an estradiol (E2) level in the premenopausal range) after surgery or after chemotherapy, whichever is later.

Patients with distant metastatic disease.

Patients with locally advanced inoperable breast cancer including inflammatory breast cancer or supraclavicular node involvement or with enlarged internal mammary nodes (unless pathologically negative) are not eligible. Patients with involved internal mammary nodes detected by sentinel node biopsy that are not enlarged are eligible.

Patients with positive final margins (referring to only DCIS and invasive cancer, not LCIS), except as noted in section 3.1.5. DCIS at a margin is permitted if a complete mastectomy has been performed.

Patients with clinically detectable residual axillary disease.

Patients with a history of prior ipsilateral or contralateral invasive breast cancer. Patients with synchronous bilateral invasive breast cancer (diagnosed histologically within 2 months) are eligible if the bilateral disease meets all other eligibility criteria (see section 8.1.2 for data management for such patients).

Patients with previous or concomitant invasive malignancy are not eligible. The exceptions are patients with the following (and only the following) malignancies (previous or concomitant) who are eligible if adequately treated:
basal or squamous cell carcinoma of the skin
in situ non-breast carcinoma without invasion
contra- or ipsilateral in situ breast carcinoma
non-breast invasive malignancy diagnosed at least 5 years ago and without recurrence:
stage I papillary thyroid cancer
stage Ia carcinoma of the cervix
stage Ia or b endometrioid endometrial cancer
borderline or stage I ovarian cancer

Patients with other non-malignant systemic diseases (cardiovascular, renal, hepatic, lung, etc.) that would prevent prolonged follow-up. Patients with previous thrombosis (e.g., DVT) and/or embolism can be included only if medically suitable.

Patients who have had a bilateral oophorectomy or ovarian irradiation. Patients who will be recommended to undergo oophorectomy within 5 years (e.g., BRCA1 / 2 gene carriers) and therefore for whom randomization to a treatment arm without OFS is inappropriate.

Patients with a history of noncompliance to medical regimens and patients who are considered potentially unreliable.

Patients who are pregnant or lactating at the time of randomization or who desire a pregnancy within 5 years. Patients planning to use additional hormonal therapy apart from the randomized treatment (see Section 5.3.1) during the next five years including all types of hormonal contraception. A pregnancy test is recommended for women of child-bearing potential who are sexually active and not using reliable contraceptive methods.

Patients who received endocrine therapy (including neoadjuvant and adjuvant) for more than 8 months after their breast cancer diagnosis. Patients who are receiving endocrine therapy at randomization (and have received it for less than 8 months) may continue such therapy until protocol-specified tamoxifen/exemestane is initiated (see section 5.1).

Patients who were taking tamoxifen or other SERM (e.g. Raloxifene) or hormone replacement therapy (HRT) within one year prior to their breast cancer diagnosis. Prior oral contraceptives are allowed.

Patients who have received GnRH analogues as part of their breast cancer treatment prior to random

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To compare ovarian function suppression (OFS: GnRH analogue or oophorectomy or ovarian irradiation) plus tamoxifen vs. tamoxifen alone<br><br>To compare OFS plus exemestane vs. OFS plus tamoxifen (This comparison will combine data with the IBCSG 25-02 TEXT trial as the primary analysis for the TEXT trial)<br>;Secondary Objective: To compare OFS plus exemestane vs. tamoxifen alone;Primary end point(s): Disease-free survival;Timepoint(s) of evaluation of this end point: 2013 Q3 at a median follow up of approximately 5 years

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): - Overall survival<br>- Breast cancer-free interval and distant recurrence-free interval<br>- Quality of life<br>- Sites of first treatment failure<br>- Late side effects of early menopause<br>- Incidence of second (non-breast) malignancies<br>- Causes of death without cancer event;Timepoint(s) of evaluation of this end point: 2013 Q3 at a median follow up of approximately 5 years