E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
HER2-negative metastatic breast cancer after failure of no more than two chemotherapy regimen in two cohorts of patients; Two Cohorts: Cohort A: Triple negative metastatic breast cancer, i.e. HER2-negative, estrogen-receptor-negative and progesterone receptor negative; Cohort B:HER2-negative, estrogen-receptor-positive and/or progesterone-receptor positive;
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 8.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10027475 |
E.1.2 | Term | Metastatic 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 evaluate the efficacy, safety and pharmacokinetics of BIBW 2992 in two cohorts of patients with HER2-negative breast cancer, after failure of no more than two regimen of prior chemotherapy. Cohort A includes patients with HER2-negative, estrogen- receptor-negative, progesterone-receptor-negative, i.e. triple negative tumours. Cohort B includes patients with HER2-negative, estrogen-receptor-positive and/or progesterone-receptor-positive tumours. |
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E.2.2 | Secondary objectives of the trial |
Secondary objectives are to look at clinical benefit (CR, PR, SD), time to objective response, duration of objective response, time to tumour progression, progression-free survival, overall survival, safety of BIBW 2992 as indicated by intensity and incidence of adverse events, graded according to NCI CTCAE version 3.0, especially skin reactions and GI adverse events, cardiac left ventricular function, evaluation of population pharmacokinetics, evaluation of quality of life;
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Inclusion criteria for both cohorts of HER2-negative patients 1. Female Patients age 18 years or older. 2. Patients with histologically proven breast cancer, who failed or relapsed after no more than two lines of chemotherapy, including adjuvant. 3. HER2-negative patients (HER2 1+ or negative, or Her2 2+ and FISH negative if known). 4. Patients with at least one tumour lesion that can accurately be measured by magnetic resonance imaging (MRI), computed tomography (CT) or X-ray in at least one dimension (longest diameter to be recorded) as ≥ 20 mm with conventional techniques or as ≥ 10 mm with spiral CT scan. 5. Patients must have tumour samples available for EGFR-testing. 6. Life expectancy of at least six (6) months. 7. Written informed consent that is consistent with ICH-GCP guidelines and local law. 8. Eastern Cooperative Oncology Group (ECOG) performance score 0 or 1. 9. Evidence of metastatic breast cancer
Additional inclusion criteria for Cohort A
10. HR-negative patients; ER-status and PgR-status must be assessed by IHC.
Additional inclusion criteria for Cohort B
10. ER-and/or PgR-positive patients; ER-status and PgR-status must be assessed by IHC.
11. Patients must sign informed consent form for pharmakogenetic analyses prior to analysis of EGFR/EGFR-ligand overexpression on mRNA basis. |
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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 diarrhoea. 3. Serious illness, concomitant non-oncological disease or mental problems 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 cerebral 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/mm3. 7. Platelet count less than 100 000/mm3. 8. Bilirubin greater than 1.5 mg /dl (>26 µmol /L, SI unit equivalent). 9. Aspartate amino transferase (AST) or alanine amino transferase (ALT) greater than 2.5 times the upper limit of normal or greater 5 times the upper limit of normal in case of known liver metastases. 10. Serum creatinine greater than 1.5 mg/dl (>132 µmol/L, SI unit equivalent). 11. Patients 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; other anti-cancer-therapy, e.g. chemotherapy, immunotherapy, radiotherapy or hormone therapy (including LHRH agonists, or other endocrine therapies/hormones taken for breast cancer), concomitantly with therapy on this study. Previous small field radiation or endocrine therapy during the past two weeks, myelosuppressive chemotherapy within the past four weeks, and therapy with mitomycin C during the past six weeks prior to the first treatment with the trial drug. Concurrent treatment with biphosphonates is allowed. 14. Previous treatment with trastuzumab, EGFR-, or EGFR/HER2-inhibitors. 15. Patients unable to comply with the protocol. 16. Active alcohol or drug abuse. 17. Patients who have not recovered from any therapy-related toxicities of previous chemo-, hormone-, immuno-, or radiotherapies at the time of the first administration of the trial drug. 18. Other malignancy within the past 5 years |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint will be the objective response (CR, PR), determined by RECIST criteria for Cohort B and clinical benefit (CB), i.e. CR, PR and SD for a minimum of 4 months, for Cohort A |
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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 | 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 | Yes |
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 | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 12 |
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 | Yes |
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 clinical trial will be considered completed as soon as the last patient has completed her last visit. In case the trial will be finished by the sponsor when patients are still being treated with the trial drug, the patients cannot continue to receive 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 | 3 |
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 | 3 |