E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Progression of an advanced (locally advanced or metastatic) Her2-negative breast cancer after anthracycline and/or taxane pretreatment |
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E.1.1.1 | Medical condition in easily understood language |
Worsening of advanced (locally or metastatic) breast cancer. Surface marker of breast cancer cells Her2 has to be negative and patients have to be previously treated with (antracycline and/or taxane) |
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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 | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10006187 |
E.1.2 | Term | 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 |
The efficacy of a capecitabine plus bendamustine combination regimen in the treatment of Her2-negative advanced metastatic breast cancer, in terms of overall response rates (complete or partial Response)
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E.2.2 | Secondary objectives of the trial |
To determine the safety profile of a combination with capecitabine and bendamustine in terms of qualitative and quantitative toxicities from first study treatment dose until completion of study treatment due to progression or for any other reason. To evaluate the study population with respect to the following: clinical benefit (CR, PR or stable disease for at least 24 weeks), progression free survival (from treatment start until progression or death from any cause) and explorative the overall survival (from treatment start until death from any cause). To evaluate Quality of Life (QoL) status within the study population is captured using the EORTC QLQ-C30 standard questionnaire. Predefined subgroup analysis of triple-negative patients and hormone receptor positive patients in terms of response |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Signed informed consent Female patients, age ≥ 18 years (women of childbearing potential must have a negative pregnancy test at screening and must use effective contraception) Advanced or metastatic Her2-negative breast cancer, histologically confirmed At least one measurable lesion according to RECIST criteria (Version 1.1) Documented disease progression Patients with progression after anthracycline and/or taxane treatment (palliative or neoadjuvant or adjuvant) Life expectancy of at least 12 weeks Performance status 0-2 Adequate hematology, liver and renal function: Hematologic: ANC (absolute neutrophil count) ≥ 1.5 x 109/L Hemoglobin ≥ 9 g/dL Platelets ≥ 100 x 109/L Liver Function: Albumin ≥ 2.5 g/dL Serum bilirubin ≤ 2 mg/dL AST and ALT ≤ 3 x ULN without liver metastases ≤ 5 x ULN if documented liver metastases Renal Function: Serum Creatinine ≤ 1.5 mg/dL OR Calculated Creatinine Clearance ≥ 40 mL/min
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E.4 | Principal exclusion criteria |
Pregnant or lactating women Serious medical or psychiatric disorders that would interfere with the patient’s safety or informed consent Radiation of the target lesion within the last 4 weeks Active bacterial, viral or fungal infection Patients with clinically apparent brain metastases Known Positivity for HIV Positivity for Hepatitis B or C History of other malignancy; patients who have been disease-free for 5 years or patients with a history of completely resected non-melanoma skin cancer or successfully treated in situ carcinoma are eligible. Concurrent cancer therapy (chemotherapy, immunotherapy, antihormonal or biologic therapy) or concurrent treatment with an investigational drug Antihormonal therapy must have been discontinued prior to start of treatment (if possible at least 3 weeks before) Known hypersensitivity to the study drugs capacitabine and bendamustine or their excipients Pretreatment with capecitabine (pretreatment with infusional 5-FU in the adjuvant or neoadjuvant setting is allowed) or bendamustin Treatment with sorivudine or derivates e.g. brivudin (Mevir©) within the last 4 weeks before and during study treatment with capecitabine
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E.5 End points |
E.5.1 | Primary end point(s) |
Overall Response Rates (ORR)
Primary outcome variable Overall tumor response rates (complete response (CR) or partial response (PR), determined by radiologic evaluation according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1) [23]
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Efficacy and safety will be evaluated following recruitment of the first 20 patients. Upon favorable results a further 20 patients will be recruited and efficacy and safety will be evaluated at end of the study. Last Subject Last Visit will be at final staging after end of treatment of last Patient. |
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E.5.2 | Secondary end point(s) |
Progression free survival (PFS) Clinical benefit (CR, PR or stable disease for at least 24 weeks) Safety profile of a combination with capecitabine and bendamustine Quality of Life
Secondary outcome variables Safety: qualitative and quantitative toxicities Overall survival Progression free survival Change in quality of life (measured with the global scale of the EORTC QLQ-C30, BR 23) from the time of screening up to the time of study end. Predefined subgroup analysis of triple-negative patients and hormone receptor positive patients in terms of Response. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Efficacy and safety will be evaluated following recruitment of the first 20 patients. Upon favorable results a further 20 patients will be recruited and efficacy and safety will be evaluated at end of the study. Last Subject Last Visit will be at final staging after end of treatment of last Patient. |
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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 | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
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 | No |
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) | 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
| 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 | 8 |
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 | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
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 last patient is expected to enter the study in Q1 2015, following a 24 month recruitment period. Last Subject Last Visit will be at final staging after end of treatment of last patient. |
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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 | 5 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | |