E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Premenopausal women, Early Stage I, II or IIIA, ER-/ PR- Breast Cancer
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 8.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10006190 |
E.1.2 | Term | Breast cancer invasive NOS |
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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 |
The primary objective of this study is to compare the rate of premature ovarian failure at two years following standard adjuvant or neoadjuvant chemotherapy with or without the addition of ovarian suppression with a LHRH analog during chemotherapy in premenopausal women with early stage, hormone-receptor negative breast cancer. |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives are to compare rates of ovarian dysfunction at one year and two years following standard adjuvant or neoadjuvant chemotherapy with or without ovarian suppression and to evaluate ovarian reserve in the two groups at one and two years. In addition, this study will describe pregnany and other fertility information in the two groups after treatment and during the five year follow-up period. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Patient must be premenopausal women with a histologically confirmed diagnosis of operable Stage I, II, or IIIA invasive breast cancer. Patients who have completed surgery must have pathologic Stage I, II or IIIa disease. Patients to be treated in the preoperative setting may be staged clinically but must have operable disease. For the purposes of this study, premenopausal is defined as the presence of cyclic menstrual bleeding within 6 weeks prior to randomization or documentation of FSH and estradiol levels in the premenopausal range.
Patients must have tumors that are both estrogen receptor negative and progesterone receptor negative. The definition of hormone receptor negativity will be that used by the registering institution, with the following exceptions: a. tumors with > 10% cells staining positive for either ER and/or PR on immunohistochemistry assay will be considered receptor positive b. tumors with > 3 fm/mg cytosol protein on ligand-binding or EIA assay will be considered receptor positive Patients with bilateral synchronous invasive breast cancer diagnosed within 1 month of each other are eligible only if both primary tumors are hormone receptor negative.
Patients must be of age 18 or greater and under age 50.
The patient's planned treatment must include 3 to 8 months or cycles of an alkylating agent containing post-operative or pre-operative chemotherapy regimen that can be anthracycline-based or non-anthracycline-based. Patients must not start the planned chemotherapy prior to registration to S0230.
Patients receiving post-operative chemotherapy must be registered within 84 days after the final surgical procedure required to adequately treat the primary tumor or axilla.
Patient must have a performance status of 0-2 by Zubrod criteria.
All patients must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines.
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E.4 | Principal exclusion criteria |
No prior malignancy is allowed except for adequately treated basal cell (or squamous cell) skin cancer, in situ cancer or other cancer for which the patient has been disease-free for five years after treatment with curative intent.
Pregnant or nursing women may not participate due to the possibility of fetal harm or of harm to nursing infants from this treatment regimen. Women of reproductive potential must agree to use an effective barrier contraceptive method.
For patients receiving chemotherapy in the pre-operative setting, there must be no intention to give additional chemotherapy in the postoperative setting (i.e., all chemotherapy should be completed prior to surgery).
Patients must not have received prior cytotoxic chemotherapy for this breast cancer or for any condition.
Patients must not have received estrogens, antiestrogens, selective estrogen receptor modulators, aromatase inhibitors, or hormonal forms of contraception within the past month with the following exceptions: Women under the age of 35 may have had recent use of oral contraceptive pills but these must be discontinued prior to randomization. In addition, for women of all ages, up to two months of hormonal treatment for oocyte collection for the purposes of in vitro fertilization and cryopreservation of embryos or oocytes is permitted provided these treatments are completed prior to randomization. Women using oral contraceptive pills or hormonal treatments for oocyte collection during the month prior to enrollment must have documentation of FSH and estradiol levels in the premenopausal range.
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is the rate of ovarian failure at 2 years from initiation of chemotherapy. Ovarian failure at two years is defined as amenorrhea (absence of menstrual bleeding) for the preceding six months and the presence of FSH in the post-menopausal range. |
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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 | No |
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) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
Without ovarian protection |
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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.8.4.1 | Number of sites anticipated in Member State concerned | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 8 |
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 |
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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
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All patients will be followed for 5 years from date of initiation of chemotherapy. Measurements of ovarian dysfunction/reserve will be obtained at months 12/13 and 24/25 after initiation of chemotherapy. Fertility will be assessed during 5 year follow-up. |
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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 | 8 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 8 |