E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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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 | 10055113 |
E.1.2 | Term | Breast cancer metastatic |
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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 |
Part 1: 1. To determine the Maximum Administered Dose (MAD) and the Dose Limiting Toxicities (DLTs) of XRP9881 administered as a 1-hour infusion every 3 weeks in combination with capecitabine (Xeloda®) tablets twice daily for 2 weeks in 3-week cycles. 2. To determine the Maximum Tolerated Dose (MTD)) of XRP9881 in combination with capecitabine. The MTD, (determined once the MAD has been reached in the part 1) , will be used in the part 2 of the study to assess the antitumor response.·
Part 2: To determine the antitumor activity, in an additional cohort of patients with metastatic breast cancer (MBC) with disease progressing after anthracycline and taxane, of XRP9881 in combination with Xeloda® as assessed by objective response according to RECIST. |
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E.2.2 | Secondary objectives of the trial |
· To assess the safety profile of the combination regimen of XRP9881 with capecitabine. · To assess the pharmacokinetic (PK) profile of XRP9881 in combination with capecitabine and to evaluate any PK interaction between capecitabine, its metabolite and XRP9881. . To determine the Progression Free Survival (PFS), Duration of response, Composite of clinical event of CR, PR, and stable disease ≥ 12 weeks of the extended cohort of patients treated in the part 2 of the study |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Histologically or cytologically proven diagnosis of breast adenocarcinoma that is now metastatic or locally recurrent and inoperable with curative intent. Patients with previously treated histo/cytologically confirmed disease who develop clinical or radiological evidence of metastatic disease do not require separate confirmation of the metastatic disease.
2. Patients must have received an anthracycline and a taxane prior to entry in the protocol. These drugs may have been given in the neoadjuvant/adjuvant or in the metastatic setting, may have been given concurrently or sequentially, and may have been given in combination with other drugs. Patients should have received a standard dose of anthracycline and of taxane expected to have potentially resulted in a response. For Part I only, patients who have received at least a prior regimen with either an anthracycline or a taxane are eligible
3. Female patients at least 18 years old.
4. Evidence of measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST). For the part I component, patients with non-measurable disease are accepted
5. Completion of all prior chemotherapy, biological therapy, targeted non-cytotoxic therapy, and radiotherapy ≥ 3 weeks prior to registration. For part 2 only, Prior treatment with radiotherapy, chemoembolization therapy, or cryotherapy is allowed if these therapies are not directed to the areas of measurable disease being used for the purposes of this protocol.
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E.4 | Principal exclusion criteria |
1. 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 patients with any other in situ cancer or a history of an invasive cancer with complete remission for 5 or more years must be discussed with the sponsor and the principal investigator. Patients with a history of contralateral breast cancer who have been disease-free for more than 5 years prior to registration are permitted.
2. The following breast cancer treatments for part II only: a. Patients receiving more than one adjuvant regimen. However, patients who have received neoadjuvant therapy immediately followed by surgery and immediately followed by adjuvant therapy without intervening progression are considered to have received one adjuvant regimen and are allowed in the trial. b. Patients receiving more than one chemotherapy regimen 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. For example, patients who received sequential doxorubicin and docetaxel in the metastatic setting without intervening progression are allowed in the trial as this is considered one CT regimen.
3. Known brain or leptomeningeal disease (CT or MRI scan of the brain required only in case of clinical suspicion of central nervous system involvement).
4. Prior treatment with capecitabine, XRP9881 or any investigational chemotherapy. Docetaxel, Paclitaxel (and generic) and Abraxane® (nanoparticle albumin-bound paclitaxel ) are permitted.
5. History of hypersensitivity grade ≥ 3 to taxanes, Polysorbate-80, or to compounds with similar chemical structures. Patients with known intolerance to fluoropyrimidines or patients with known dihydropyrimidine dehydrogenase (DPD) deficiency.
6. Peripheral neuropathy grade ≥ 2.
7. Any of the following within the 6 months prior to registration: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft surgery, clinically symptomatic and uncontrolled cardiovascular disease, or clinically significant cardiac arrhythmias (grade 3-4).
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E.5 End points |
E.5.1 | Primary end point(s) |
In the part 1 of the study, DLTs of the combination of XRP9881 and capecitabine in MBC patients progressing after antracycline and taxane therapy.
In the part 2, efficacy will be determined using objective responses (CR and PR) as assessed by investigators according to RECIST criteria. Confirmation of objective responses will be performed by repeat tumor imaging (CT scans, MRI) 4-6 weeks after the first radiological documentation of response. |
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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 | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
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) | Yes |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | Yes |
E.7.1.3.1 | Other trial type description |
to study the combination of XRP9881 and capecitabine |
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E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
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) | 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
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
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 | No |
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 study is expected to be approximately 18 months including 12 months for enrollment and 6 months for follow-up after last patient last visit. |
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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 | 1 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 6 |