E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
The medical condition under investigation is HER-2 positive metastatic breast cancer. Patients will have progressed on, or be intolerant of, treatment with trastuzumab (Herceptin). |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10055113 |
E.1.2 | Term | Breast cancer metastatic |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10065430 |
E.1.2 | Term | HER-2 positive breast cancer |
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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 investigate the effectiveness of BIBW 2992 in treating HER2 positive breast cancer patients who have failed, or cannot tolerate, treatment with trastuzumab (Herceptin).
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E.2.2 | Secondary objectives of the trial |
The secondary objectives are: 1) to determine the time taken to achieve a response to treatment 2) to determine the duration of response 3) to determine the time to disease progression 4) to determine the duration of progression-free survival 5) to determine overall survival rates 6) to determine the incidence and intensity of adverse events |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Male or female patients with confirmed diagnosis of Stage IIIB or IV HER2-positive metastatic breast cancer (HER2 2+ and FISH positive or HER2 3+). 2. Patients must have progressed following receipt of prior standard trastuzumab treatment or standard chemotherapy in conjunction with trastuzumab. Patients with visceral disease or rapid progression should not be included if they have not had previous chemotherapy in addition to trastuzumab. Patients who are intolerant to trastuzumab and who have received adequate chemotherapy and/or hormone therapy are eligible upon progression. 3. Age 18 years or older. 4. Life expectancy of at least four (4) months. 5. Written informed consent that is consistent with ICH-GCP guidelines. 6. Eastern Cooperative Oncology Group (ECOG, R01-0787) performance Score 0, 1 or 2. 7. Patients should not have received treatment with chemotherapy or immune therapy within the last 4 weeks (2 weeks for trastuzumab). Patients should also not have received treatment with hormone therapy within the last 2 weeks. 8. Patients must have recovered from any therapy-related toxicities from previous chemo-, hormone-, immuno-, or radiotherapies to CTC less than or equal to Grade 1. 9. Patients must have recovered from previous surgery. 10. Patients must have measurable disease as defined by RECIST criteria. |
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E.4 | Principal exclusion criteria |
1. Active infectious disease. 2. Gastrointestinal disorders that may interfere with the absorption of the study drug or chronic diarrhea. 3. Serious illness or concomitant non-oncological disease considered by the investigator to be incompatible with the protocol. 4. Patients with active/symptomatic brain metastases. Patients with a history of treated brain metastases must have stable or normal MRI scan at screening and be at least three months post-radiation or surgery. 5. Cardiac left ventricular function with resting ejection fraction <50%. 6. Absolute neutrophil count (ANC) less than 1500 cells/mm3. 7. Platelet count less than 100 000 cells/mm3. 8. Bilirubin greater than 1.5 mg/dl (>26 micromol /L, SI unit equivalent). 9. Aspartate amino transferase (AST) or alanine amino transferase (ALT) greater than three times the upper limit of normal. 10. Serum creatinine greater than 1.5 mg/dl (>132 micromol/L, SI unit equivalent). 11. Women and men (and their partners) who are sexually active and unwilling to use a medically acceptable method of contraception. 12. Pregnancy or breast-feeding. 13. Treatment with other investigational drugs; chemotherapy, immunotherapy, radiotherapy or hormone therapy (including LHRH agonists, or other hormones taken for breast cancer), or participation in another clinical study within the past 4 weeks before start of therapy or concomitantly with this study. Treatment with bisphosphonates is allowed. 14. Prior treatment with an EGFR- or HER2 inhibiting drug (except trastuzumab). 15. Patients unable to comply with the protocol. 16. Active alcohol or drug abuse. 17. Patients with history of other malignancy (except for appropriately treated superficial basal cell skin cancer and surgically cured cervical cancer in situ) unless free of disease for at least 3 years.
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint of this study is objective response (CR, PR) by RECIST criteria for HER2-positive metastatic breast cancer patients treated with BIBW 2992 following trastuzumab failure. |
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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 | No |
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 | No |
E.8.1.1 | Randomised | Information not present in EudraCT |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
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) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
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 | 6 |
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 | 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 | 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 study medication will be provided to patients for as long as there is a clinical benefit without a reason for withdrawal. The trial will end when the last patient to finish medication completes the follow-up visit.
The primary analysis will be performed upon data recorded up until the time that the last patient undergoing treatment either completes 24 weeks, progresses, or discontinues trial medication. Later data will be summarised in an addendum to the clinical trial report. |
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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 | 4 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 6 |