Estrogen receptor positive, hormone refractory, metastatic breast adenocarcinoma MedDRA version: 8.1 Level: LLT Classification code 10006187 Term: Breast cancer
Conditions
Sponsors
Boehringer Ingelheim France S.A.S.
Eligibility
Sex/Gender
All
Inclusion criteria
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 =65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
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) 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 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.;Secondary Objective: 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. ;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 progre | — |
Countries
France
Outcome results
None listed