| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| HER2 - overexpressing breast cancer |
|
| E.1.1.1 | Medical condition in easily understood language |
|
| 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 | 19.0 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10057654 |
| E.1.2 | Term | Breast cancer female |
| E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 19.0 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10006202 |
| E.1.2 | Term | Breast cancer stage IV |
| E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 19.0 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10055113 |
| E.1.2 | Term | Breast cancer metastatic |
| E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
| 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 efficacy and safety of BIBW 2992 (afatinib) alone and in combination with weekly treatment with paclitaxel or vinorelbine (in patients who progress on BIBW 2992 (afatinib) monotherapy only) as a new treatment algorithm in patients with HER2-overexpressing, metastatic breast cancer, who failed HER2-targeted treatment in the neoadjuvant and/or adjuvant setting.
The primary endpoint is Objective Response (OR) assessed by RECIST 1.1 |
|
| E.2.2 | Secondary objectives of the trial |
The secondary and other endpoints for this study are:
1. Best overall response during each treatment period according to RECIST 1.1
2. Duration of objective response
3. Progression-Free Survival (PFS)
4. Safety assessed by the severity and incidence of adverse event according to Common Terminology Criteria for Adverse Events (Version 3.0), changes in vital signs and safety laboratory parameters
5. Incidence of new brain metastases
6. ECOG performance status
7. Overall survival
8. Percentage change from baseline in tumour size
|
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1.Female patients ≥18 years
2. Proven diagnosis of HER2-overexpressing, histologically confirmed breast cancer, Patients must have an archived tissue sample available for central re-assessment of HER2-status.
3.Stage IV metastatic disease.
4. At least one measurable lesion according to RECIST 1.1. Skin, bone and brain lesions are considered non-target lesions.
5. Life expectancy of at least six (6) months.
6. Must have failed or progressed trastuzumab or lapatanib or trastuzumab and
lapatanib treatment in the neoadjuvant and/or adjuvant setting and on BIBW
2992 (afatinib) monotherapy in the 1st line metastatic setting (for patients in the second part of the trial).
|
|
| E.4 | Principal exclusion criteria |
1. Requirement for treatment with any of the prohibited concomitant medications
2. Quickly progressing visceral disease
3. Known pre-existing interstitial lung disease
4. Prior first line therapy for metastatic breast cancer
5. Radiotherapy, chemotherapy, immunotherapy, trastuzumab or lapatinib treatment or surgery (other than biopsy) within 4 weeks prior to trial treatment. Treatment with palliative radiotherapy (short course to non-target lesions) is allowed.
6. Hormone therapy for breast cancer within 2 weeks prior to trial treatment
7. Active brain metastases (defined as stable for <4 weeks and/or symptomatic and/or requiring changes of treatment with anticonvulsants or steroids and/or leptomeningeal disease).
8. Any other current malignancy or malignancy diagnosed within the past five (5) years (other than bilateral primary breast cancer, metastases to the contralateral breast, non-melanomatous skin cancer and in situ cervical cancer).
9. Significant or recent acute gastrointestinal disorders with diarrhoea as a major symptom e.g. Crohn's disease, malabsorption or CTC grade ≥2 diarrhoea of any aetiology.
10. History or presence of clinically relevant cardiovascular abnormalities such as uncontrolled hypertension, congestive heart failure NYHA classification of 3, unstable angina or poorly controlled arrhythmia
11. Myocardial infarction within 6 months prior to trial treatment.
12. Cardiac left ventricular function with resting ejection fraction of less than 50%
13. Absolute neutrophil count (ANC) < 1.5 x 109/L
14. Calculated Creatinine clearance < 60 ml / min (Cockcroft formula – Appendix 1) or serum creatinine > 1.5 times upper limit of normal
15. Bilirubin > 1.5 times upper limit of normal.
16. Aspartate amino transferase (AST) or alanine amino transferase (ALT) > three times the upper limit of normal (ULN) (if related to liver metastases > five times ULN).
17. Prior treatment with paclitaxel in the past 12 months.
18. Platelet count < 100 x 109/L
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Objective Response (OR) assessed by RECIST 1.1 |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| In each trial part (monotherapy and combination-therapy) objective response will be calculated based on the best response to therapy (according to RECIST 1.1). Response to therapy will be evaluated every six weeks from start of monotherapy and then every six weeks from start of combination therapy until end of treatment. |
|
| E.5.2 | Secondary end point(s) |
• Best overall response during each treatment period according to RECIST 1.1
• Duration of objective response, defined as the time from first objective response to the time of progression or death.
• Progression-Free Survival (PFS) will be defined for three time intervals: time from the date of the start of monotherapy to the date of 1st disease progression; time from the date of the start of combination therapy to the date of 2nd disease progression and the time from the date of the start of monotherapy to the date of 2nd disease progression. In each case, the date of death will be used if a patient died before the appropriate progression. The analysis will be based upon the evaluation of tumour imaging performed by the investigator using RECIST Version 1.1.
• Safety assessed by the severity and incidence of adverse event according to Common Terminology Criteria for Adverse Events (CTC s, AE Version 3.0), changes in vital signs and safety laboratory parameters
|
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
Response to therapy and duration of objective response will be evaluated every 6 weeks from start of monotherapy and then every 6 weeks from start of combination therapy until end of treatment. Progression free survival will be calculated based on response to therapy (according to RECIST 1.1) and vital status.
Occurrence of adverse events will be recorded at every study visit up to the first follow-up visit (and at subsequent follow-up visits if ongoing at first follow-up visit or treatment related). Vital signs will be evaluated at every visit. Specimens for evaluation of laboratory tests will be obtained at the screening visit, at the start of each 3-weekly treatment course, at the end of treatment visit and at each follow-up visit. |
|
| 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 | 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 | 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 | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 17 |
| 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 | No |
| 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 |
| Poland |
| Romania |
| United Kingdom |
|
| 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
|
| The trial will be considered complete when the last patient completes the last follow-up visit. |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 4 |
| E.8.9.1 | In the Member State concerned months | 6 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 4 |
| E.8.9.2 | In all countries concerned by the trial months | 6 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
Print
