| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated | | Metastatic breast cancer patients after failure to anthracyclines, taxanes and capecitabine. | |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Classification code | 10055113 | |
| 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 determine the objective response rate of RPR109881 administered as a 1-hour infusion every 3 weeks in patients with metastatic breast cancer (MBC) relapsing or progressing after therapy with anthracyclines, taxanes, and capecitabine. | |
| E.2.2 | Secondary objectives of the trial | -To assess the safety and tolerability of RPR109881 in this patient population.
-To assess the impact of RPR109881 on pain control and analgesic use.
-To assess the impact of RPR109881 on the maintenance of performance status and body weight.
-To determine the effect of RPR109881 on clinical benefit as assessed by time to tumor response, duration of response, Progression Free Survival, and overall survival.
-To assess the effect of single administration of 90mg/m2 RPR109881 on the pharmacokinetic profile of simvastatin single dose of 40mg in a subgroup of patients. | |
| E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
| E.3 | Principal inclusion criteria | -Histologically or cytologically proven diagnosis of breast adenocarcinoma that is now metastatic or locally recurrent and inoperable. Patients with previously treated histo/cytologically confirmed disease who develop clinical or radiological evidence of metastatic disease do not required separate confirmation of the metastatic disease.
-Patients must have been previously treated with an anthracycline, taxanes (docetaxel and/or paclitaxel), and capecitabine. These treatments may have been given in the adjuvant or metastatic setting, separately or combined. Patients must have received a standard dose of anthracycline, taxane and capecitabine expected to have potentially resulted in a response.
-Evidence of measurable disease as defined by RECIST.Measurable lesions are lesions that can be accurately measured in at least one dimension with longest diameter superior or equal to 20mm. With spiral CT scan ,lesion must be superior or equal to 10mm in at least one dimension (slice thickness= 5-8 mm).
-Completion of all prior chemotherapy, immunotherapy (including trastuzumab [Herceptin®]), targeted non-cytotoxic therapy, and radiotherapy superior or equal to 3 weeks prior to first treatment dose on study. Prior treatment with radiotherapy, chemoembolization therapy, or cryotherapy is allowed if these therapies did not affect the areas of measurable disease being evaluated for efficacy in this protocol. Patients may start or continue to receive bisphosphonate therapy as clinically indicated.
-ECOG performance status of 0,1 or 2.
-Patients who received chemotherapy in the adjuvant setting must not have received more than two previous chemotherapy regimens ( ie, a single or a combination of chemotherapy agents given until documented disease progression or relapse) for metastatic or locally recurrent and inoperable breast cancer. Patients who did not receive chemotherapy in the adjuvant setting must not have received more than three previous chemotherapy regimens for metastatic or locally recurrent and inoperable breast cancer. A chemotherapy regimen is defined as a single or a combination of chemotherapy agents given until documented disease progression or relapse.
| |
| E.4 | Principal exclusion criteria | -History of any second malignancy with the exception of adequately treated basal cell or squamous cell skin cancer, or in situ carcinoma of the cervix uteri. Inclusion of any other in situ cancer must be discussed with the sponsor. Patients with adequately treated contralateral breast cancer which has been disease-free for more than 5 years prior to first treatment dose on study are eligible.
-Concurrent treatment with other anti-cancer therapy, including chemotherapy, immunotherapy (including trastuzumab [Herceptin®]), hormonal therapy, radiotherapy, chemoembolization therapy, cryotherapy, targeted therapy, or patients planning to receive these treatments.
-Concurrent treatment with strong inhibitors of cytochrome P450 3A4, such as ketoconazole, itraconazole, clarithromycin or patients planning to receive these treatments. For patients who were receiving treatment with such agents, a one-week washout period is required before first treatment dose on study.
-Prior treatment with epothilones or with non-approved tubulin-interacting agents. Prior treatment with Abraxane® (nanoparticle albumin-bound paclitaxel) is permitted.
-Prior participation in any other trials that involve RPR109881 with a survival endpoint to avoid compromising the results of such trials.
-HER2-positive patients may participate in this trial. Concurrent treatment with trastuzumab (Herceptin®) is not permitted.
-Known symptomatic brain or leptomeningeal involvement with cancer. Patients with a history of symptomatic brain involvement with cancer (i) must have had these lesions previously surgically removed or irradiated; (ii) must not be treated currently with corticosteroids; and (iii) must have documentation that the lesions are stable or improving by CT or MRI scan performed at least 3 months apart. For such patients, a baseline CT or MRI scan must be obtained less than or equal to 21 days prior to the first treatment dose on study.CT or MRI scan of the brain is required only in case of clinical suspicion of central nervous system involvement. Patients with asymptomatic untreated brain lesions are not excluded.
-Known human immunodeficiency virus (HIV) infection currently requiring therapy, or acquired immunodeficiency syndrome (AIDS)-related illness.
-Patients who are pregnant or breastfeeding. | |
| E.5 End points |
| E.5.1 | Primary end point(s) | | The primary efficacy variable is the Response Rate (RR) defined as the proportion of patients with confirmed CR or confirmed PR, defined by RECIST criteria, relative to the total number of patients in the analysis population. | |
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | Information not present in EudraCT |
| E.6.2 | Prophylaxis | Information not present in EudraCT |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Information not present in EudraCT |
| E.6.7 | Pharmacodynamic | Information not present in EudraCT |
| E.6.8 | Bioequivalence | Information not present in EudraCT |
| E.6.9 | Dose response | Information not present in EudraCT |
| E.6.10 | Pharmacogenetic | Information not present in EudraCT |
| E.6.11 | Pharmacogenomic | Information not present in EudraCT |
| E.6.12 | Pharmacoeconomic | Information not present in EudraCT |
| E.6.13 | Others | Yes |
| E.6.13.1 | Other scope of the trial description | |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | Information not present in EudraCT |
| E.7.1.1 | First administration to humans | Information not present in EudraCT |
| E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
| E.7.1.3 | Other | Information not present in EudraCT |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | Information not present in EudraCT |
| E.7.4 | Therapeutic use (Phase IV) | Information not present in EudraCT |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | No |
| 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 | No |
| 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) | Information not present in EudraCT |
| E.8.2.2 | Placebo | Information not present in EudraCT |
| E.8.2.3 | Other | Information not present in EudraCT |
| 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 | | The duration of this study is expected to take approximately 42 months, which includes the time necessary for the confirmatory radiological study to be performed (no less than 4 weeks after the criteria for response are met initially) on the last patient enrolled who responds after two cycles of therapy and for the determination of stable disease (requiring follow-up of 12 weeks or longer). | |
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | |
| 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 | 3 |
| E.8.9.2 | In all countries concerned by the trial months | 6 |
