| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
|
| MedDRA Classification |
| 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 demonstrate that the combination of capecitabine (825 mg/m2 twice daily d1-14) and docetaxel (75 mg/m2) d1 Q3W is at least equivalent to the combination of capecitabine (1250 mg/m2 twice daily d1-14 ) and docetaxel (75 mg/m2) d1 Q3W in terms of time to disease progression or death due to any cause. |
|
| E.2.2 | Secondary objectives of the trial |
- To evaluate and compare the safety profile of each of the two regimens of capecitabine plus docetaxel combination therapy using the NCI CTC (Version 3.0).
- To evaluate in each study arm overall response rate (complete and partial responders according to RECIST criteria), time to response and duration of overall response (in responding patients), time to treatment failure, and overall survival.
- To investigate the effect of long term co-administration of capecitabine and docetaxel on the pharmacokinetics of capecitabine and docetaxel.
- To evaluate the effect of age on efficacy, toxicity, dose, and pharmacokinetics |
|
| E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
| E.3 | Principal inclusion criteria |
1. Give written informed consent prior to study specific screening procedures, with the understanding that the patient has the right to withdraw from the study at any time without prejudice
2. Be female and > 18 years of age.
3. Be ambulatory and have a Karnofsky performance status of > 70%
4. Have histologically or cytologically confirmed breast cancer with locally advanced and/or metastatic disease
5. Have at least one target lesion according to the RECIST criteria (see Appendix 4 of the protocol for details of RECIST). Target lesions measured solely by PET scan will be acceptable if ≥ 2cm in longest diameter.
6. Have met one of the study definitions of primary or non-primary resistance to an anthracycline-containing therapy, as modified from Piccart (1995) [39]:
Primary resistance: Patients progressing on anthracycline-based chemotherapy, without experiencing any transient improvement, Non-Primary resistance: Patients whose disease remains stable after administration of a minimum of four cycles of anthracycline-based chemotherapy, Patients experiencing a brief objective response to anthracycline-based chemotherapy with subsequent progression while on the same therapy or within 12 months after last dose, Patients relapsing within 2 years of the completion of an anthracycline-based neoadjuvant or adjuvant chemotherapy regimen
|
|
| E.4 | Principal exclusion criteria |
1. Pregnant or lactating women
2. Women of childbearing potential with either a positive or no pregnancy test at baseline
3. Women of childbearing potential unless using a reliable and appropriate contraceptive method.
4. Chemotherapy within four weeks preceding treatment start
5. Prior treatment with more than two regimens of chemotherapy in the advanced/metastatic (non-adjuvant) setting
6. Prior treatment with continuous (>24h) 5-FU infusion, capecitabine or other oral fluoropyrimidines such as eniluracil/5-FU, uracil/tegafur, S1 or emitefur
7. Prior treatment with a docetaxel-containing regimen in the advanced/metastatic disease setting
8. Mitomycin C or Nitrosoureas within 6 weeks preceding treatment start, 9.Organ allografts (excluding bone marrow auto- or allografts)
10. Radiotherapy to the axial skeleton within the 4 weeks preceding study treatment start or insufficient recovery from the effects of prior radiotherapy
11. Hormonal therapy within 10 days preceding study treatment start
12. Incomplete recovery from the effects of major surgery
13. Blood transfusions or growth factors to aid hematologic recovery within 2 weeks prior to study treatment start
14. Participation in any investigational drug study within 4 weeks preceding treatment start
15. Prior unanticipated severe reaction to fluoropyrimidine therapy (with or without documented DPD deficiency)
16. Known hypersensitivity to 5-fluorouracil, any of the components of capecitabine or docetaxel
17. Severe renal impairment (creatinine clearance <30 mL/min [calculated according to Cockroft and Gault
18. Evidence of CNS metastases
19. History of another malignancy within the last five years except cured basal cell carcinoma of skin and carcinoma in–situ of uterine cervix or a contralateral breast cancer
20. Clinically significant (i.e. active) cardiac disease (e.g. congestive heart failure, symptomatic coronary artery disease and cardiac arrhythmia not well controlled with medication) or myocardial infarction within the last 12 months
21. Abnormal laboratory values:
• hemoglobin <8.0 g/dl, neutrophils < 1.5 x 109/L, platelet count < 100 x 109/L
• serum creatinine > 1.5 x Upper Limit of Normal (ULN)
• serum bilirubin > ULN
• ALAT(SGPT) and/or ASAT(SGOT) > 5 x ULN (1.5 x if alkaline phosphatase is concomitantly elevated ≥ 2.5 x ULN)
• alkaline phosphatase > 5 x ULN (except when bone metastases are present in the absence of any liver disorders)
• serum calcium >11.5 mg/dL
22. Serious uncontrolled intercurrent infections
23. Lack of physical integrity of the upper gastrointestinal tract or those who have clinically significant malabsorption syndrome
25. Life expectancy of less than 3 months
27. Requirement for concurrent use of the antiviral agent sorivudine or chemically related analogues, such as brivudine.
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Time to tumor progression or death (TTP) |
|
| 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 | 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) | 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 | 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) | No |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | Yes |
| E.8.2.3.1 | Comparator description |
| Combination of approved products |
|
| 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
|
| Last patient last visit after last tumor assessment |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 5 |
| 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 | 5 |
Print
