E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
A multi-centre phase I-II study to investigate the combination of bendamustine with weekly paclitaxel as first or second line therapy in patients with metastatic breast cancer |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 13.1 |
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 determine the maximum tolerated dose of the combination of bendamustine and weekly paclitaxel (phase I part) • To determine the time to progression achievable with the recommended dose of this combination (phase II-part)
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E.2.2 | Secondary objectives of the trial |
• To determine the objective response rate (phase II-part) • To determine the safety and tolerability of the combination • To determine the dose-limiting toxicity (DLT) (grade IV haematological toxicities or grade III non-haematological toxicities)
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Written informed consent must be obtained and documented according to the local regulatory requirements prior to beginning specific protocol procedures; • Pathological confirmed primary carcinoma of the breast. • Locally advanced or metastatic disease • Up to one previous palliative chemotherapy that did not contain docetaxel or paclitaxel. Previous adjuvant treatment with taxanes is allowed when the last application of the taxane was given at least 1 year before entering the trial. • Patients must have either measurable or non-measurable lesions according to the WHO criteria • At least 4 weeks since radiotherapy, with full recovery. The measurable disease must be completely outside the radiated field or there must be pathological proof of progressive disease. • Complete radiology and tumour assessment within 4 weeks prior to registration performed as clinically indicated; • Karnofsky-Index ≥60%, • Age ≥18 years • Absolute neutrophil count ≥1,500 cells/µl, platelets ≥100,000/µl, and haemoglobin ≥9g/dl • Bilirubin within normal limits; evaluation of transaminases and alkaline phosphatase ≤ 5x upper normal limit • Creatinine ≤ 2.0mg/dl • Normal left ventricular ejection fraction (LVEF) by echocardiogramme • Patients with childbearing potential, pregnancy test must be negative • If fertile effective contraception must be used throughout the study
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E.4 | Principal exclusion criteria |
• Known hypersensitivity reaction to the investigational compounds or incorporated substances; • Concurrent immunotherapy or hormonal treatment for cancer (Bisphosphonates may be continued) • Symptomatic parenchymal brain metastases not responding to treatment • Life expectancy less than 3 months • Other serious illness or medical condition that may interfere with the understanding and giving of informed consent and the conduct of the study • Prior or concomitant secondary malignancy (except non-melanomatous skin cancer or carcinoma in situ of the uterine cervix) • Concurrent treatment with other experimental drugs or any other anti-cancer therapy within the last 28 days; • History of congestive heart failure or other significant uncontrolled cardiac disease • Pregnant or nursing women
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E.5 End points |
E.5.1 | Primary end point(s) |
• the maximum tolerated dose of the combination of bendamustine and weekly paclitaxel (phase I part) • the time to progression achievable with the recommended dose of this combination (phase II part)
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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 | 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) | Yes |
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 | 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 | Information not present in EudraCT |
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.8.5 | 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 | Information not present in EudraCT |
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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |