study of abituzumab in combination with cetuximab and folfiri in patients with metastatic colorectal cancer.

Conditions: Metastatic Colorectal Cancer

Summary: the purpose of this study is to evaluate the safety and efficacy of the experimental drug abituzumab (emd525797) in combination with cetuximab and folfiri in ras wild-type, left-sided, metastatic colorectal cancer patients with high ανβ6 integrin expression.


Eligibility criteria:
inclusion criteria: 1. signed and dated written informed consent prior to any study specific procedure; 2. age: ≥18 years; 3. evidence of newly diagnosed stage iv metastatic colorectal cancer. primary tumor location on the left side of the colon (including left splenic flexure) or rectum; 4. demonstrated wild-type ras mutation status in the tumor (primary tumor or metastasis) by local assessment; 5. tumor tissue specimen shows high ανβ6 integrin expression, as determined by central laboratory assessment; 6. tumor tissue specimen (formalin-fixed, paraffin-embedded block) preferably from primary resection and/or if available from a surgical sample from metastatic site must be available for central laboratory based ανβ6 integrin expression analysis. (no fine needle aspiration \[fna\] will be accepted); 7. at least 1 radiographically documented measurable lesion in a previously non-irradiated area according to recist (version 1.1), i.e., this lesion must be adequately measurable in at least 1 dimension (longest diameter to be recorded) as ≥2 cm by conventional techniques or ≥1 cm by spiral ct scan; 8. eastern cooperative oncology group (ecog) performance status (ps) 0-1; 9. females of childbearing potential must have a negative pregnancy test at screening and be willing to have additional pregnancy tests during the study; exclusion criteria: 1. demonstrated any ras or braf mutation; 2. prior anti-egfr or other targeted therapy; 3. prior chemotherapy of the colorectal cancer, except for (neo) adjuvant therapy completed at least 6 months before randomization; 4. radiotherapy (localized radiotherapy for pain relief is allowed to non-target lesions); 5. investigational drug treatment for the treatment of malignancies in the past; 6. concurrent participation in another interventional clinical study; 7. pregnancy (exclusion confirmed with beta-hcg test) or lactation; 8. any history or evidence of brain metastases or leptomeningeal metastases; 9. history of secondary malignancy within the past 5 years, except for basal cell carcinoma or carcinoma in situ of the cervix uteri, if treated with curative intent; 10. concomitant chronic systemic immune or hormone therapy not indicated in this study protocol (except for physiologic replacement; steroids up to 10 mg per day of prednisone equivalent or topical and inhaled steroids are allowed); 11. clinically relevant coronary artery disease (new york heart association \[nyha\] functional angina classification iii/iv), congestive heart failure (nyha iii/iv), or clinically relevant cardiomyopathy; 12. uncontrolled hypertension defined as systolic blood pressure \>160 mmhg and/or diastolic blood pressure \>100 mmhg under resting conditions; 13. history of myocardial infarction in the last 12 months, or a high risk of uncontrolled arrhythmia, coagulation disorder associated with bleeding or recurrent thrombotic events, with the exception of arterial fibrillation treated with anti-coagulants; 14. recent peptic ulcer disease (endoscopically proven) within 6 months of randomization, chronic inflammatory bowel disease, or acute/chronic ileus; 15. active infection (requiring iv antibiotics and/or antiviral therapy), including active tuberculosis, active or chronic hepatitis b or c, or ongoing hiv infection, aids; 16. presence of any contra-indications or known hypersensitivity to treatment with abituzumab, cetuximab, and folfiri, or to any of the excipients of these drugs; 17. concomitant treatment with prohibited medications; 18. medical or psychological conditions that would not permit the patient to complete the study.