Dose Finding Study of Twice Weekly IMMU-130 in Metastatic Colorectal Cancer

This is a Phase I, open-label study of IMMU-130 administered in 21-day treatment cycles, twice weekly for 2 consecutive weeks followed by one week of rest to patients with metastatic colorectal cancer who have been previously treated with at least one prior irinotecan-containing regimen. The study is being done to evaluate whether the study drug is safe and tolerable at different dose levels with this dosing schedule.

• Metastatic Colorectal Cancer
• Colon Cancer
• Rectal Cancer

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Inclusion Criteria:

• Male or female patients, ≥ 18 years of age, able to understand and give written informed consent.
• Histologically or cytologically confirmed colorectal adenocarcinoma.
• Stage IV (metastatic) disease.
• Previously treated with at least one prior irinotecan-containing regimen for colorectal cancer.
• Adequate performance status (ECOG 0 or 1). (Appendix 1)
• Expected survival > 6 months.
• CEA plasma levels > 5 ng/mL.
• Measurable disease by CT or MRI.
• At least 4 weeks beyond treatment (chemotherapy, immunotherapy and/or radiation therapy) or major surgery and recovered from all acute toxicities.
• At least 2 weeks beyond corticosteroids.
• Adequate hematology without ongoing transfusional support (hemoglobin > 9 g/dL, ANC > 1,500 per mm3, platelets > 100,000 per mm3).
• Adequate renal and hepatic function (creatinine ≤ 1.5 x IULN, bilirubin ≤ IULN, AST and ALT ≤ 3.0 x IULN or 5 x IULN if know liver metastases).
• Otherwise, all toxicity at study entry ≤ Grade 1 by NCI CTC v4.0.

Exclusion Criteria:

• Women who are pregnant or lactating.
• Women of childbearing potential and fertile men unwilling to use effective contraception during study until conclusion of 12-week post-treatment evaluation period.
• Patients with Gilbert's disease or known CNS metastatic disease.
• Patients with CEA plasma levels > 1000 ng/mL are excluded during dose escalation, but may be included after the MTD is determined.
• Presence of bulky disease (defined as any single mass > 10 cm in its greatest dimension).
• Patients with active ≥ grade 2 anorexia, nausea or vomiting, and/or signs of intestinal obstruction.
• Patients with non-melanoma skin cancer or carcinoma in situ of the cervix are eligible, while patients with other prior malignancies must have had at least a 3-year disease-free interval.
• Patients known to be HIV positive, hepatitis B positive, or hepatitis C positive.
• Known history of unstable angina, MI, or CHF present within 6 months or clinically significant cardiac arrhythmia (other than stable atrial fibrillation) requiring anti-arrhythmia therapy.
• Known history of clinically significant active COPD, or other moderate-to-severe chronic respiratory illness present within 6 months.
• Infection requiring intravenous antibiotic use within 1 week.
• Other concurrent medical or psychiatric conditions that, in the Investigator's opinion, may be likely to confound study interpretation or prevent completion of study procedures and follow-up examinations.