E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Metastatic breast cancer patients progressing after taxanes and anthracyclines therapy. |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Classification code | 10055113 |
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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 |
To compare time to progression in patients with metastatic breast cancer treated with RPR109881 versus capecitabine progressing after taxanes and anthracycline therapy. |
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E.2.2 | Secondary objectives of the trial |
- To compare survival and other measures of anti-tumor efficacy [response rate (RR), time to tumor response (TTR), duration of response (DR), single time progression rate (STPR), and time to treatment failure (TTF)] in patients treated with RPR109881 versus capecitabine.
- To compare the safety and tolerability of RPR109881 versus capecitabine.
- To compare the quality of life and other clinical benefit measures in patients treated with RPR109881 versus capecitabine. |
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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 (TXNXM1) or locally recurrent and inoperable with curative intent.
- All patients must have received an anthracycline and a taxane prior to entry in the protocol. These drugs may have been given in the adjuvant or in the metastatic setting, may have been given concurrently or sequentially, and may have been given in combination with other drugs. Patients must have received a standard dose of anthracycline and of taxane expected to have potentially resulted in a response. For taxanes: a) Patients must have progressed while receiving paclitaxel or docetaxel therapy or at any time after having received paclitaxel or docetaxel therapy. b) The taxane-based treatment must have been the last chemotherapy the patient received. For anthracyclines: Patients must have either: a) Progressed while on anthracycline treatment, with or without an initial response, OR b) Patients must have received an adequate course of anthracyclines defined as follows: i. In the adjuvant setting, patients must have received a regimen considered standard for adjuvant therapy, which would usually result in a cumulative dose of doxorubicin of 240-300 mg/m2 or doxorubicin equivalent. ii. In the metastatic setting patients must have received a regimen considered standard for therapy for metastatic disease, which would usually result in a cumulative dose of doxorubicin of at least 300 mg/m2 or doxorubicin equivalent.
- Evidence of measurable disease as defined by RECIST.
- Completion of all prior chemotherapy, immunotherapy (including trastuzumab [Herceptin]), targeted non-cytotoxic therapy, and radiotherapy 3 weeks or more than 3 weeks prior to study entry.
- ECOG (Eastern Cooperative Oncology Group) performance status of 0,1, or 2. |
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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 a history of contralateral breast cancer who have been disease-free for more than 5 years prior to randomization are permitted.
- Prior treatment with capecitabine or any taxanes analogs except for paclitaxel or docetaxel (eg, epothilones are not permitted, novel preparations of paclitaxel are not permitted, generic paclitaxel is permitted).
- Known brain or leptomeningeal disease (CT or MRI scan of the brain required only in case of clinical suspicion of central nervous system involvement).
- Concurrent treatment on another clinical trial or with any other cancer therapy including chemotherapy, immunotherapy (including trastuzumab [Herceptin]), hormonal therapy, radiotherapy, chemoembolization therapy, cryotherapy, targeted non-cytotoxic therapies or patients planning to receive these treatments during the study.
- Known human immunodeficiency virus (HIV) infection requiring treatment or acquired immunodeficiency-syndrome (AIDS)-related illness.
- HER-2 positive patients may participate in this trial. Concurrent treatment with trastuzumab [Herceptin] is not permitted.
- Concurrent treatment with potent inhibitors of cytochrome P450 3A4, such as ketoconazole, itraconazole, erythromycin, clarythromycin or patients planning to receive these treatments. For patients who were receiving treatment with such agents, a one-week washout period is required prior to randomization.
- Patients who are pregnant or breastfeeding. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Time to tumor progression (TTP) will be determined by the Independent Review Committee (IRC) and defined as the time from randomization to first documentation of objective tumor progression, according to RECIST, or death. |
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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 |
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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) | Information not present in EudraCT |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
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 | 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 |
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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
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The duration of this study is expected to be 20 months or until the observation of the required number of events needed for the final analysis of time-to-progression (October 2005). |
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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 | |
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 | 9 |