E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Estrogen receptor positive, hormone refractory, metastatic breast adenocarcinoma |
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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 | 10006187 |
E.1.2 | Term | 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 determine the progression-free rate after 16 weeks of BIBW 2992 administration adding to standard aromatase inhibitor letrozole, in patients with estrogen receptor positive, letrozole refractory metastatic breast cancer. |
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E.2.2 | Secondary objectives of the trial |
1. Occurrence and intensity of adverse events graded according to CTCAE version 3.0,
2. Objective response (complete response, partial response) based on RECIST criteria
3. Clinical benefit rate (complete response, partical response, stable disease according to RECIST) at 16 and 24 weeks
4. Time to RECIST tumor response
5. Duration of RECIST tumor response
6. Progression-free survival,
7. Overall survival,
8. Pharmacokinetic parameters of BIBW 2992 and letrozole
9. Biological studies based on tumor biopsy analyses will be conducted to identify the biomarkers which are involved during the progression of the disease.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Female patients with histologically proven breast adenocarcinoma,
2. Age ≥ 18 years,
3. Presence of metastatic disease,
4. Chemo-naïve patients (no prior chemotherapy for metastatic disease; patients who have received adjuvant chemotherapy including trastuzumab for early breast cancer in the past are eligible),
5. Patients with estrogen receptor positivity (IHC ≥ 10%) on the most recently examined tumor biopsy,
6. Patients must currently be on letrozole and developed acquired resistance as defined by disease progression on letrozole following previous response (partial response or better, or stable disease ≥ 24 weeks),
7. Diagnosis of disease progression ≤ 6 weeks prior to trial entry defined as: a. Increase in the number of bone lesions on bone scan or on MRI, AND/OR b. Increased pain in an area of known bony metastasis AND ≥ 2 serial elevations in CA 15-3, AND/OR c. Progression according to RECIST criteria on CT scan, MRI, or x-ray,
8. Patients must have documented menopause confirmed by estradiol level < 11 pg/ml (patients having medical ovarian suppression by LHRH analogues will be excluded),
9. Estimated life expectancy ≥ 6 months,
10. ECOG performance status 0 or 1,
11. Patient must be able to comply with the protocol,
12. Patients should not have received treatment with chemotherapy, radiotherapy, or immune therapy within the last 4 weeks prior to study enrolment,
13. Patients must have recovered from any grade 3 (according to US CTCAE version 3.0) adverse events from previous treatment,
14. Patient must have signed and dated written informed consent form. |
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E.4 | Principal exclusion criteria |
1. Active or uncontrolled infectious disease,
2. Gastrointestinal disorders that may interfere with the absorption of the study drugs or chronic diarrhea or difficulty to swallow,
3. Premenopausal patients,
4. Serious illness or concomitant non-oncological disease considered by the investigator to be incompatible with the protocol,
5. History of other malignancies in the last 5 years, which could affect compliance with the protocol or interpretation of results. Patients with adequately treated basal or squamous cell carcinoma of skin and cervical carcinoma in situ are generally eligible,
6. Rapidly progressive disease in major organs (i.e., lymphangitic spread in the lung and/or bulky liver metastasis),
7. Patient with brain metastasis,
8. Significant cardiovascular diseases (i.e. uncontrolled hypertension, unstable angina, history of infarction, congestive heart failure > NYHA II) within the past 12 months,
9. Cardiac left ventricular function with resting ejection fraction inferior to the normal value,
10. Absolute neutrophil count (ANC) < 1500/mm3,
11. Platelet count < 100 000/mm3,
12. AST and/or ALT > 3x ULN (In case of known liver metastases AST and/or ALT > 5 x ULN),
13. Serum creatinine > 1.5 mg/dL (>132 µmol/L, SI unit or equivalent),
14. Concomitant treatment with any other investigational device or drugs, chemotherapy, immunotherapy, radiotherapy, or participation in another clinical study within the past four weeks before start of therapy or concomitantly during the study. Treatment with bisphosphonates are allowed during the study, as long as patient has been on a stable dose for at least 3 months prior to study entry),
15. Previous treatment with an EGFR and/or HER-2 inhibiting drug (Patients who received trastuzumab only in the adjuvant setting can be enrolled),
16. Active alcohol or drug abuse. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Progression-free rate after 16 weeks of treatment, where progression is defined according to one of the following criteria: • New bone lesion(s) on bone scan or on MRI, • Progression or occurrence of new lesion(s) according to RECIST criteria, • Increase of CA 15-3 of more than 20% compared to the baseline value at 2 consecutive exams, • Occurrence of disease-related skeletal events (pathological or vertebral compression fracture not related to trauma; palliative radiotherapy for bone pain; prophylactic radiation or surgery for an impending fracture, spinal cord compression).
Palliative radiotherapy for bone pain during the first 4 weeks of treatment will not be considered as a criteria for progression if according to the investigator’s judgment the increase in bone pain can be attributed to flare up in a previously know bone metastatic site. The diagnosis of progression should essentially be based on the above criteria. However if a patient does not fulfil any of the above criteria and is withdrawn from the study because of clinical deterioration amounting to progressive disease according to the investigator, the patient will be considered as having progressive disease. |
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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 | Yes |
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 | Yes |
E.6.13.1 | Other scope of the trial description |
Tmour sample analyses to investigate activation of receptor pathways |
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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 | 4 |
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 | 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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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 | 5 |
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 | 5 |