| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
Premenopausal women with histologically proven, resected breast cancer with ER
and/or PgR positive tumors for whom there is an uncertain role for adding chemotherapy to the adjuvant treatment program |
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 7.0 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10057654 |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| To compare ovarian function suppression plus tamoxifen or exemestane vs. chemotherapy plus ovarian function suppression plus tamoxifen or exemestane |
|
| E.2.2 | Secondary objectives of the trial | |
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
Premenopausal women (estradiol (E2) in the premenopausal range (per 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
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.
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 |
|
| E.4 | Principal 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.
Patients with previous or concomitant invasive malignancy EXCEPT 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 deep venous 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 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 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.
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|
| E.5 End points |
| E.5.1 | Primary end point(s) |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Yes |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
|
| E.8.7 | Trial has a data monitoring committee | Yes |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
There are two possible answers to this question depending on the context and reason for asking the question:
1. The trial will continue indefinitely as patients are to be followed life-long.
2. The primary analysis will be conducted when the target number of events described in the protocol are observed. Follow-up of patients is to continue indefinitely (life-long) to assess treatment effects on long-term outcome and to evaluate late occurring events.
|
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| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 6 |
| E.8.9.1 | In the Member State concerned months | 11 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 6 |
| E.8.9.2 | In all countries concerned by the trial months | 11 |
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