| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated | | Brain metastases from breast cancer | |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 4.0 | | E.1.2 | Level | 4 | | E.1.2 | Classification code | 10027453 | |
| 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 | | Determine the effect of efaproxiral on primary and secondary efficacy endpoints in patients with brain metastases from breast cancer receiving daily intravenous (IV) efaproxiral with supplemental oxygen (O2) administered prior to standard whole brain radiation therapy (WBRT) compared to patients receiving standard WBRT with supplemental oxygen alone | |
| E.2.2 | Secondary objectives of the trial | | Assess the safety of efaproxiral in this patient population | |
| E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
| E.3 | Principal inclusion criteria | 1- Histologically or cytologically confirmed breast cancer in women with radiographically confirmed metastases to the brain
a. patient may have dural lesion(s) as the only site of disease in the brain, only if lesion(s) are pathologically confirmed to be malignant and proof of onset after primary diagnosis of breast cancer is available
b. patient may have extracranial metastases
c. patient may have received prior treatment for breast cancer and extracranial metastases
d. patient may receive concurrent trastuzumab, hormonal and/or corticosteroid therapy
2- At least 18 years of age
3- KPS>=70
4- Adequate hematologic, hepatic and renal function:
- hemoglobin >= 10 g/dL, white blood cell count >= 2.5*10^9 cells/L; absolute neutrophil count >= 1.5*10^9 cells/L; platelet count >= 100*10^9 cells/L;
- total bilirubin <= 1.5 time the Upper Limit of Normal (ULN); aspartate aminotransferase and alanine aminotransferase <= 3 times ULN
- serum creatinine <= 1.5 mg/dL;
5- Adequate pulmonary function tests by simple spirometry, as defined by forced vial capacity and forced expiratory volume in 1 second >+ 50% of normal for patient age, gender, height and race
6- Resting arterial O2 saturation (SpO2) measured by cutaneous pulse oximetry (SpO2)>=90% while breathing room air
7- Exercise (eg walking uninterrupted for approximately 15 metres on level ground) SpO2>=90% while breathing room air
8- (criterion removed in protocol version 2.2)
9- Women of childbearing potential must be practicing a medically acceptable contraceptive regimen and must have a negative serum pregnancy test within 14 days prior to first day of WBRT. Patients who are postmenopausal for at least 1 year (>12 months) or are surgically sterilized do not require this test
10- Patient must be accessible for repeat dosing and follow-up
11- Patient must give written informed consent
| |
| E.4 | Principal exclusion criteria | 1- Active concurrent malignancy (except nonmelanoma skin cancer or in situ carcinoma of the cervix). If there is a history of prior malignancy, the patient must be disease-free for>=5 years
2- The patient is a candidate for surgical resection and/or stereotactic radiosurgery as initial therapy for brain metastases
3- Planned concurrent systemic (cytotoxic and/or cytostatic) treatment for breast cancer and/or extracranial metastases during WBRT, with the exception of trastuzumab, hormonal and/or corticosteroid therapy
4- Prior treatment for brain metastases (including external beam radiation therapy, brachytherapy, stereotactic radiosurgery, surgery, chemotherapy, and treatments with investigational drugs, biologics or devices)
5- Presence of leptomeningeal metastases
6- Use of any investigational drugs, biologics, or devices within 28 days prior to WBRT day 1
7- Previous exposure to efaproxiral
8- Women who are pregnant or lactating
9- Active infection or any serious underlying medical condition, which would impair the ability of the patient to receive protocol treatment
10- Dementia or significantly altered mental status that would prohibit the understanding and giving of informed consent | |
| E.5 End points |
| E.5.1 | Primary end point(s) | | Survival, measured from the date of randomisation | |
| 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 | Information not present in EudraCT |
| 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 | 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 | Information not present in EudraCT |
| 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 | Once the 281st death has been observed
| |
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 2 |
| 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 | 2 |
