E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Metastatic Breast Cancer (MBC) |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10027475 |
E.1.2 | Term | Metastatic breast cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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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 evaluate the efficacy of the combination of WX-671 and capecitabine
compared to capecitabine monotherapy, as assessed by comparison of
progression free survival rates. |
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E.2.2 | Secondary objectives of the trial |
To evaluate efficacy in terms of overall survival rates.
To compare objective response rates.
To compare the safety and tolerability of the combination of WX-671 and
capecitabine compared to capecitabine monotherapy.
To assess the pharmacokinetics (PK) of WX-671 in this population, and to
evaluate the PK of capecitabine when administered with WX-671. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1) Females aged ≥ 18 years.
2) Patients appropriate for palliative first-line, mono chemotherapy with capecitabine
3) Histological or cytological confirmed, non-inflammatory metastatic breast cancer
4) Availability of paraffin-embedded tumor tissue from the primary resection or biopsy of a metastatic lesion.
5) HER2-negative breast cancer (as per immunohistochemistry DAKO score 0 1; DAKO score 2 and negative FISH assay; all negative FISH assays).
6) Complete staging within 2 weeks prior to randomization (4 weeks for bone scan).
7) Radiologically confirmed disease: at least one measurable lesion according to RECIST-patients with bone metastases only are allowed
8) ECOG (Eastern Cooperative Oncology Group) performance status of ≤ 2.
9) Ability to understand and willingness to voluntarily sign and date a written informed consent form before screening, following an explanation of the nature and purpose of this study.
10) Negative pregnancy test (urine or serum) within 3 days before first study drug for women of childbearing potential. Effective contraception must be used by women of childbearing potential during the study and for 3 months after stopping study drug treatment.
11) Normal organ and marrow function as defined by laboratory parameters (obtained within the screening period) within the following limits:
• neutrophils >= 1.5 x 109/L;
• platelets >= 100 x 109/L;
• hemoglobin >= 9.0 g/dL (5.6 mmol/L).
Note: Patients may receive blood transfusions as medically appropriate during the study. Patients who require a blood transfusion during screening must have stable hemoglobin (≥ 9.0 g/dL) without the need for further transfusions during the 2 weeks before first dose of study medication in order to remain eligible;
• total bilirubin <= 1.5 x upper limit of normal (ULN);
• aspartate aminotransferase (AST)/ALT <= 2.5 x ULN (<= 5.0 x ULN for patients with liver metastases);
• serum creatinine <= 2 x ULN, or calculated creatinine clearance >45 mL/min according to Cockroft and Gault formula).
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E.4 | Principal exclusion criteria |
1) Endocrine therapy completed within 2 weeks before the start of treatment (i.e. previous hormone therapy is allowed provided that there is a washout period of 2 weeks).
2) Prior chemotherapy or biologic therapy for metastatic disease.
3) Major surgery within 4 weeks prior to the start of treatment.
4) Other anti-cancer treatment (e.g. hormones) within 2 weeks before the start of treatment.
5) Treatment within 12 months with adjuvant 5-FU containing chemotherapy (regarded as indicating 5-FU resistance) and/or prior capecitabine therapy.
6) Radiation therapy for the metastatic disease. Palliative radiation of stable, non-target lesions more than 2 weeks before the start of treatment is allowed, provided patients have recovered from the radiation side-effects.
7) History of or radiological evidence of brain metastasis including previously treated, resected or asymptomatic brain lesions or leptomeningeal involvement.
8) Active seizure disorder or history of cerebrovascular accident (CVA) or transient ischemic (TI) attack within the past 12 months.
9) History of other malignancy within the last 3 years except for surgically cured non-melanoma skin cancer or cervical carcinoma in situ.
10) Active cardiac disease e.g. unstable angina, congestive heart failure, myocardial infarction (MI) within the preceding 6 months.
11) Any medical condition prohibiting standard imaging procedures
12) Pregnant or breast-feeding.
13) Any unrelated illness, e.g. active infection requiring parenteral antibiotics, inflammation, medical condition or laboratory abnormalities, which in the judgment of the investigator might significantly affect patients’ study participation.
14) Any surgical or medical condition that might significantly alter the absorption, distribution, metabolism or excretion of either study drug.
15) Known hepatitis B/C or HIV (human immunodeficiency virus) infection.
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E.5 End points |
E.5.1 | Primary end point(s) |
Determination of progression-free survival (PFS) following the combination of WX-671 and capecitabine vs. capecitabine monotherapy. PFS refers to the probability that a patient will remain alive, without the disease getting worse. A PFS event is defined as the time from randomization until objective tumor progression or death, whichever is first. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
ORR will be determined at 12 and 24 weeks after randomization into the study.
OS will be determined from the patient survival time after randomization into the study. An OS event will be the time from randomization until death.
Safety assessments
Pharmacokinetics (24 h profiles in 12 patients and trough levels of WX 671/WX UK1 in all patients)
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
During treatment and follow up |
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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 | Yes |
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) | 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 | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
Use Xeloda as a background treatment |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
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 | 7 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 10 |
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 | No |
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 |
Belgium |
Brazil |
Germany |
Israel |
United States |
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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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Patients will be followed until 75% of patients in each arm have died or until 2 years after first administration of study treatment in the last patient, whichever occurs first. |
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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 | 4 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |