Phase II open label trial for Inflammatory Breast Cancer patients with Afatinib and/or Vinorelbine.
- Conditions
- Health Condition 1: null- Inflammatory Breast Cancer
- Registration Number
- CTRI/2012/01/002392
- Lead Sponsor
- Boehringer Ingelheim India Pvt Ltd
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Other (Terminated)
- Sex
- Not specified
- Target Recruitment
- 40
1. Female patients >=18 years.
2. Investigator-confirmed diagnosis of Inflammatory Breast Cancer defined as a clinico-pathologic entity that is characterized by diffuse erythema and oedema (peau dâ??orange). Pathological findings of dermal lymphatic emboli or palpable mass are supportive but not necessary for diagnosis.
3. Histologically confirmed breast cancer HER2-overexpressing disease (i.e. IHC 3+ or IHC 2+ with FISH/SISH positivity). (The central lab results of any analysis of archived tissue sample are not required to be available to confirm the eligibility of the patient to take part in the study).
4. Presence of locally advanced (in the opinion of the investigator) or metastatic disease.
5. For trastuzumab pre-treated patients, must have failed prior trastuzumab treatment in the investigatorâ??s opinion.
6. Must have biopsiable disease.
7. Must have disease that can be evaluated according to RECIST 1.1.
NOTE: Patients with skin disease only may be included and their disease evaluated as non-target lesion(s) according to RECIST 1.1.
8. Eastern Cooperative Oncology Group (ECOG) score of 0, 1 or 2 (Ref: Appendix 2).
9. Life expectancy of at least six (6) months in the opinion of the investigator.
10. Written informed consent that is consistent with ICH-GCP guidelines and
local legislation.
11. In addition for Part B (afatinib and vinorelbine combination therapy), patients
must have progressed on afatinib monotherapy in Part A.
1. Prior treatment with HER2-targeted small molecules or antibodies (other than
trastuzumab which must have been given in the trastuzumab-failure study
population).
2. Requirement for treatment with any of the prohibited concomitant medications
listed in Section 4.2.2 (restrictions).
3. Must not have received prior vinorelbine in any setting.
4. Known pre-existing interstitial lung disease (ILD).
5. Radiotherapy, chemotherapy, hormone therapy, immunotherapy, trastuzumab
or surgery (other than biopsy) within 2 weeks prior to the first dose of afatinib
in Part A. Patients must have recovered from previous lines of treatment in the
investigatorâ??s opinion. Treatment with palliative radiotherapy (short course to
non-target lesions) is allowed.
6. Active brain metastases (defined as stable for less than 4 weeks and/or
symptomatic and/or requiring changes of treatment with anticonvulsants or
steroids and/or leptomeningeal disease).
7. Any other current malignancy or malignancy diagnosed or relapsed within the
past five (5) years (other than non-melanomatous skin cancer and in situ
cervical cancer).
8. Significant or recent acute gastrointestinal disorders with diarrhoea as a major
symptom e.g. Crohns disease, malabsorption or CTC grade >=2 diarrhoea of
any aetiology.
9. History or presence of clinically relevant cardiovascular abnormalities such as
uncontrolled hypertension (in the investigators opinion), congestive heart
failure NYHA classification of 3 or higher, unstable angina or poorly
controlled arrhythmia (in the investigators opinion).
10. Myocardial infarction within 6 months prior to the first dose of afatinib.
11. Cardiac left ventricular function with resting ejection fraction of less than
50%.
12. Any other concomitant serious illness or organ system dysfunction which in
the opinion of the investigator would either compromise patient safety or
interfere with the evaluation of the safety of the test drug.
13. Absolute neutrophil count (ANC) 1.5 x 109/L.
14. Platelet count 100 x 109/L for Part A (afatinib monotherapy).
Platelet count 75 x 109/L for Part B (afatinib and vinorelbine combination
therapy).
15. Calculated Creatinine clearance 60 ml / min (using Cr51-EDTA or
Cockcroft-Gault formula â?? Ref: Appendix 1) or serum creatinine 1.5 times
upper limit of normal (ULN).
16. Bilirubin 1.5 times upper limit of normal.
17. Aspartate amino transferase (AST) or alanine amino transferase (ALT) 2.5
times ULN (if related to liver metastases 5 times ULN).
18. Women of childbearing potential, unwilling to use a medically acceptable
method of contraception during the trial.
Acceptable methods of contraception include:
- Surgical sterilisation (tubal ligation/hysterectomy)
- Hormonal contraception (if applicable) with one barrier method
- Double barrier method. Double barrier method of contraception is defined as
two barrier methods used simultaneously each time the patient has intercourse.
Accepted barrier methods include diaphragm, female condom, cervical cap,
male condom and intra-uterine device (IUD) (female and male condom,
diaphragm and cervical cap must all be used in conjunction wi
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method