Metastatic colorectal cancer MedDRA version: 14.1 Level: LLT Classification code 10052362 Term: Metastatic colorectal cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: BIBW 2992 (Afatinib)
Product Code: BIBW 2992
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Afatinib
Current
Sponsors
Boehringer Ingelheim Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Histologically or cytologically proven colorectal adenocarcinoma. 2. Metastatic disease, not amenable to potentially curative treatment. 3. Tumour sample available for KRAS mutation testing and other biomarker analyses. If the patient previously had their tumour tested for KRAS mutation in another study or as part of routine clinical management, there will be no need for re-testing provided the lab that performed the test has the appropriate qualifications and certifications. A copy of this test result must be available for determination of patient’s eligibility for study entry. However, there must be adequate tumour sample remaining for analyses of other biomarkers as specified in Section 5.6. 4. Patient must have completed their previous line of treatment (i.e. last day of the last cycle) within the past 12 weeks prior to informed consent. Patients must have progressed on or after this previous line of treatment (with the exception of patients with peripheral neuropathy as per Inclusion Criteria #5) 5. Patient must have failed both oxaliplatin- and irinotecan-based regimens, whether these were given in the adjuvant or palliative setting. Patients with persistent peripheral neuropathy secondary to prior oxaliplatin who are deemed not suitable for further oxaliplatin but whose disease has not progressed on the oxaliplatin-based regimen, are eligible for this study. 6. At least one measurable lesion according to RECIST 1.1 criteria. 7. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 . 8. Age =18 years. 9. Life expectancy of at least three (3) months. 10. Complete recovery of toxicities from previous lines of anticancer therapy. An exception is peripheral neuropathy – this must have improved to = grade 2 to be eligible for this study. 11. Signed and dated written informed consent prior to admission to the study in accordance with ICH-GCP guidelines and local legislation. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Prior treatment with EGFR targeting small molecules or antibodies. 2. Radiotherapy, surgery or any major procedures (other than biopsy) within 4 weeks prior to start of study treatment. Treatment with palliative radiotherapy (short course, to non target lesions) is allowed. Any experimental anti-cancer treatment, chemotherapy, immunotherapy, hormone treatment (with the exception of megestrol acetate) must be ceased at least 4 weeks prior to start of study treatment. 3. Biological therapy (including Bevacizumab or any other anti-angiogenic agents) during the trial is not permitted. Prior treatment with these agents are allowed but they must be ceased at least 4 weeks prior to start of study treatment. 4. Planned major surgical procedures during the trial period. 5. Patients with untreated or symptomatic brain metastases. Patients with treated or asymptomatic brain metastases are eligible provided there has been no change in their brain disease status for at least 4 weeks, no history of cerebral oedema or bleeding in the past 4 weeks prior to start of study treatment. Anti-epileptic therapy is allowed provided there has not been any change in the dose of the anti-epileptic drug in the last 4 weeks prior to start of study treatment. 6. 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). 7. Known pre-existing interstitial lung disease. 8. Significant or recent acute gastrointestinal disorders with diarrhoea as a major symptom e.g. Crohn's disease, malabsorption or CTCAE grade =2 diarrhoea of any aetiology. 9. 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. Myocardial infarction within 6 months prior to start of study treatment. 10. Cardiac left ventricular function with resting ejection fraction of less than 50%. 11. 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. 12. Absolute neutrophil count (ANC) 1.5 times upper limit of normal. 16. Requirement for treatment with any of the prohibited concomitant medications listed in section 4.2.2
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Overall response rate in the study population; objective response rate in the KRAS wild type subgroup; and disease control rate in the KRAS mutated subgroup.;Secondary Objective: Progression-free survival, overall survival; safety of BIBW 2992; explorative analyses of biomarkers.;Timepoint(s) of evaluation of this end point: 6 months after start of treatment; Primary end point(s): The primary endpoint is objective response (complete response, partial response) according to RECIST 1.1 . This includes overall response rate, response rate in the KRAS wild-type subgroup and disease control rate (complete response, partial response, stable disease) in the KRAS mutated subgroup. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Progression-free survival, Overall survival, safety of BIBW 2992, explorative analysis of biomarkers, pharmacokinetic analysis;Timepoint(s) of evaluation of this end point: 6 months after start of study treatment | — |
Countries
United Kingdom
Contacts
Public ContactQRPE PSC CT Information Disclosure
Boehringer Ingelheim Pharma GmbH & Co. KG
Outcome results
None listed