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 | Level | LLT |
E.1.2 | Classification code | 10006285 |
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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 |
Primary To assess the antitumor activity of single agent gimatecan given orally on a 5 days on, 2 days off schedule for 2 weeks every 28 days as salvage treatment in female patients with advanced, breast cancer who have failed anthracycline /taxanes-based chemotherapy.
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E.2.2 | Secondary objectives of the trial |
Secondary To define the safety profile of gimatecan therapy given 5 days on, 2 days off schedule for 2 weeks every 28 days To define the tolerability of a 5 days on, 2 days off schedule for 2 weeks every 28 days To determine the time to progression (TTP) To evaluate plasma pharmacokinetics of gimatecan treatment in participating centers
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
1. Women with histologically/cytologically confirmed diagnosis of primary breast cancer 2. Presence of locally advanced to metastatic disease non-amenable to surgery or radiation therapy with curative intent 3. A maximum of 2 prior chemotherapies (which must have included previous treatment with anthracyclines and taxanes) for advanced disease (3 in case of a prior adjuvant chemotherapy). 4. At least one measurable (target) lesion according to RECIST criteria. Previously irradiated lesions will not be considered as target lesions. 5. Age > 18 years and < 75 years 6. ECOG performance status < 1. 7. Adequate hematological function: hemoglobin > 9 g/dl; neutrophils > 1.5 x 109/L; platelets > 150 x 109/L; 8. LVEF > 50% (or according to UNL of the Center) evaluated by means of ultrasound 9. Adequate liver and renal function - alkaline phosphatase 1.5 x UNL, if bone metastases present, hepatic isoenzyme should be <1.5 UNL - total serum bilirubin 1.5 times UNL regardless of liver involvement secondary to tumor - ALT, AST 1.5 x UNL ( 2.5 x UNL in presence of liver metastases) - albumin > 2.5 g/dl - creatinine 1.5mg/dL or 133 mol/l 10. All previous therapies, including hormones, must have been discontinued > 4 weeks before study entry and all acute toxicities (excluding alopecia) of any prior therapy must have resolved to NCI-CTC (Version 2.0) Grade ≤1. 11. Life expectancy of at least 3 months. 12. Evidence of a signed and dated informed consent document indicating the patient (or legally acceptable representative) has been informed of all pertinent aspects of the study 13. Willingness and ability to comply with the study protocol for the duration of the trial.
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E.4 | Principal exclusion criteria |
1. Prior radiation therapy to > 30% bone marrow 2. Active infection. 3. Any investigational agent received ≤ 4 weeks prior to study entry and/or concurrent enrolment in another clinical trial . 4. Prior high dose chemotherapy treatment requiring hematopoietic stem cell rescue. 5. Previous major gastrointestinal surgery that could alter absorption or motility (i.e. active peptic ulcer, inflammatory bowel disease, known intolerance to lactose, malabsorption syndromes, intestinal sub-occlusion or previous major gastrointestinal surgery). 6. Inability to swallow 7. Presence of serious cardiac (congestive heart failure, angina pectoris, myocardial infarction within one year prior to study entry, uncontrolled hypertension or arrhythmia), neurological or psychiatric disorder. 8. Presence of uncontrolled intercurrent illness or any condition which in the judgement of the investigator would place the subject at undue risk or interfere with the results of the study. 9. Previous concomitant malignancy at other site, other than basal or squamous cell carcinoma of the skin or in situ cervical carcinoma within 5 years. 10. Symptomatic brain metastases or leptomeningeal disease requiring therapy. 11. Pregnancy or lactation or unwillingness to use adequate method of birth control
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint of the study is the objective response rate measured according to RECIST criteria induced by gimatecan, administered orally for 5 days on 2 days off schedule for 2 weeks every 28 days. |
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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 | No |
E.6.4 | Safety | No |
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 | 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
| 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 |
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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 | 1 |
E.8.9.1 | In the Member State concerned months | 3 |
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 |