BNC101: This phase I trial is trying to determine the most appropriate dose of BNC101, an anti-cancer stem cell drug, given alone and in combination with chemotherapy for the treatment of metastatic colorectal cancerA Phase I, Dose Escalation Study of BNC101 (Anti-LGR5 Humanized Monoclonal Antibody) in Patients With Metastatic Colorectal Cancer.

Exclusion

1. Inability to comply with study and follow-up procedures (including, but not limited to: geographical or administrative reasons, and planned vacation absences for more than 7 consecutive days during the study).
2. Women who are pregnant or lactating.
3. Colorectal cancer patients going on to receive 1st line therapy for metastatic disease.
4. Treatment with chemotherapy, immunotherapy, biologic therapy, or radiation therapy as cancer therapy within 4 weeks before initiation of study treatment. Six weeks should have elapsed if prior chemotherapy treatment included nitrosoureas or mitomycin C.
5. Treatment with any other investigational agent or participation in another clinical trial with therapeutic intent within 28 days prior to Day 1 of Cycle 1.
6. Patients who have received antibody-based therapies within 28 days or 5 half-lives of the agent, whichever is longer.
7. Major surgery, other than diagnostic surgery, within 6 weeks before first study drug administration.
8. Clinically detectable (by physical exam) third-space fluid collections (e.g., ascites or pleural effusion) that cannot be controlled by drainage or other procedures prior to study entry.
9. Any uncontrolled medical or psychiatric risk factors which would contraindicate the use or impair the ability of the patient to provide informed consent, receive protocol therapy or may impose excessive risk to the patient.
10. Central nervous system (CNS) metastases, unless previously treated and well-controlled for at least 3 months (defined as clinically stable, no edema, no steroids and stable in 2 scans at least 4 weeks apart). Patients who display signs or symptoms of CNS metastases or should be imaged with CT or magnetic resonance imaging (MRI) of the head. Should metastases, including meningeal deposits be detected, these patients will not be treated with BNC101.
11. Current use of medications that may have the potential of QTc prolongation (refer to Appendix 1). If the need for use of these medications arises during the study, a discussion with and approval by the sponsor would be required.
12. History of allergy or hypersensitivity to Chinese Hamster Ovary cell products, any compound of the BNC101 formulation, or any of the chemotherapy agents to be used in this study.
13. Active uncontrolled bacterial, viral, or fungal infection, requiring systemic therapy.
14. Patient has known infection with human immunodeficiency virus (HIV), Hepatitis B or Hepatitis C, alcoholic or other hepatitis, or cirrhosis.
15. Inability to be venipunctured and/or tolerate venous access.
16. Second malignancies within 5 years prior to enrolment, except for those with a negligible risk of metastasis or death, such as adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer, localized prostate cancer treated surgically with curative intent, ductal carcinoma in situ treated surgically with curative intent.
17. Active autoimmune disease that is not controlled by nonsteroidal anti-inflammatory drugs, inhaled corticosteroids, or the equivalent of > 10 mg/day prednisone.
18. Seizure disease requiring current anticonvulsant treatment.
19. History of inflammatory bowel disease (active or past) or active peptic ulcer disease.
20. History of chronic leukemias (e.g., chronic lymphocytic leukemia).
21. History of previous, whole abdomen radiation therapy (or total pelvic radiation therapy in rectal cancer patients) or more than Grade 1 residual toxicity from previous radiation therapy. NOTE: Patients with previous standard, routine abdomino-pelvic radiotherapy are eligible and not encompassed by this criterion, which only applies to whole abdomen or total pelvic radiotherapy.
22. Patients with high cardiovascular risk, including, but not limited to coronary stenting in the previous 3 months or myocardial infarction in the past year [Patients with New York Heart Association (NYHA) class I classification are acceptable].
23. Congenital or acquired long QT syndrome.
24. QTc prolongation defined as a QTc interval greater than or equal to 450 msec at baseline; interval determination will be based on a mean value obtained from 3 baseline ECGs obtained at least 5 minutes apart.
25. Patients with history of interstitial lung disease, history of slowly progressive dyspnea and unproductive cough, sarcoidosis, silicosis, idiopathic pulmonary fibrosis, pulmonary hypersensitivity pneumonitis or multiple allergies.