Study of Abituzumab in Combination With Cetuximab and FOLFIRI in Patients With Metastatic Colorectal Cancer.

AMELION: A Randomized, Double Blinded, Phase 2, Efficacy and Safety Study of Abituzumab (EMD 525797) in Combination With Cetuximab and FOLFIRI Versus Placebo in Combination With Cetuximab and FOLFIRI in First-line RAS Wild-type, Left-sided, Metastatic Colorectal Cancer Patients With High ανβ6 Integrin Expression.

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.

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.