A Phase III Trial Evaluating the Role of Exemestane Plus GnRH Analogue as Adjuvant Therapy for Premenopausal Women with Endocrine Responsive Breast Cancer - Tamoxifen and Exemestane Trial (TEXT)

Phase 1

• Conditions: Premenopausal women with histologically proven, resected breast cancer with ERand/or PgR positive tumors; MedDRA version: 19.0Level: PTClassification code 10057654Term: Breast cancer femaleSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

• Registration Number: EUCTR2004-000168-28-DE
• Lead Sponsor: GBG Forschungs GmbH

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2006-09-05
• Last Update Posted: 27 June 2016

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Female
• Target Recruitment: 2639

Inclusion Criteria

Premenopausal women [patients should have estradiol (E2) in the premenopausal range (according to institution parameters) 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 should be
randomized within 12 weeks after definitive surgery.

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. Biochemical determination alone is not acceptable. Detailed guidelines for assessments of ER and PgR are given in the Appendix III.

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 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 performed down to the pectoral fascia and all tumor has been removed. Likewise, if all other margins are clear, a positive anterior (superficial; abutting skin) margin is permitted provided the surgeon
documents that all tumor has been removed. Radiation therapy to the conserved breast is required.

Either axillary lymph node dissection (pathological examination of at least 6 nodes
recommended) or a negative axillary sentinel node biopsy [pN0(sn)] is required. Patients with negative or microscopically axillary positive sentinel nodes (pN1mi: micrometastasis none > 2.0mm) do not require further axillary therapy. Those with positive sentinel nodes must have either an axillary dissection or radiation of axillary nodes.

For IBCSG centers, patients must have completed baseline Quality of Life (QL) Forms prior to randomization. The only exceptions are cognitive or physical impairment that interferes with QL assessment or inability to read any of the languages available on IBCSG QL forms. For non- IBCSG centers, extent of participation in the QL study is to be determined at the activation of the trial for each cooperative group (see Appendix VII for Group-specific guidelines).

Written informed consent must be signed and dated by the patient and the investigator prior to randomization.

Patients must be accessible for follow-up.

Patients must be informed of and agree to data and tissue material transfer and handling, in accordance with national data protection guidelines.

Patients must be informed of and agree to the investigations required by the protocol for translational

Exclusion Criteria

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

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 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 any neoadjuvant or adjuvant endocrine therapy after their breast cancer diagnosis.

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 received any prior neoadjuvant or adjuvant chemotherapy. Neoadjuvant or adjuvant trastuzumab (Herceptin®) is allowable, as it is not considered to be chemotherapy for eligibility determination.

Patients with psychiatric, addictive, or any disorder that would prevent compliance with protocol requirements.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Secondary Objective: ;Primary end point(s): Disease-free survival;Main Objective: To compare GnRH analogue plus exemestane vs. GnRH analogue plus tamoxifen<br><br>To investigate patient and tumor features that may contribute to inter-individual variability of responsiveness to GnRH analogue plus exemestane and GnRH analogue plus tamoxifen