Study of TF2 Carcinoembryonic Antigen (CEA) Antibody in Patients With Metastatic Colorectal Cancer

Inclusion Criteria:

• Male or female patients, >18 years of age.
• documented histologic or cytologic diagnosis of metastatic (Stage IV) colorectal cancer.
• must have at least one confirmed and measurable tumor lesion (a confirmed tumor site is one in which either biopsy-proven evidence of disease or progressive growth has been radiographically observed).
• Patients must have failed standard therapy or for whom no standard therapy exists.
• Patients must have a Karnofsky performance status of ≥ 70% (or equivalent ECOG 0-1) and an expected survival of ≥ 3 months.
• Patients who previously received a chimeric, CDR-grafted (humanized), or human IgG will be eligible provided pre-study evaluations demonstrate no significant anti-antibody reactivity with TF2.

• Hematologic parameters: WBC counts must be ≥ 3000/mm3, granulocytes

  • 1500/mm3, and platelets ≥ 100,000/m3.
• Non-hematologic parameters: Patients without liver metastases must have bilirubin ≤ 1.5 institutional upper limit of normal (IULN), whereas bilirubin in patients with known liver metastases must be <2.5-times the IULN. AST/ALT must not be >2.5 times IULN.
• At least 2 weeks beyond corticosteroids, except low doses (i.e., 20 mg/day of prednisone or equivalent) to treat nausea or other illness such as rheumatoid arthritis.
• Patients able to understand and give written informed consent. Informed consent must be obtained prior to baseline studies for enrollment purposes.

Exclusion Criteria:

• Women who are pregnant or lactating. Women of childbearing potential and fertile men will be informed as to the potential risk of procreation while participating in this trial and will be advised that they must use effective contraception during and for a period of 3 months.
• Patients with plasma CEA >1000 ng/mL or lesions exceeding 10 cm in diameter.
• Patients with severe anorexia or other gastrointestinal-related symptomatology (e.g., nausea, vomiting).
• Patients with known HIV or hepatitis B or C.
• Patients with an active second primary malignancy at the time of study entry, with the exception of carcinoma in situ of the cervix.
• Patients with known metastatic disease to the central nervous system.
• Patients with evidence of bone marrow metastases. Screening only required for patients with suspicion of metastases. Patients with ≥ 25% bone marrow involvement are excluded.
• Patients who are, in the opinion of the investigator, unable to comply with the protocol requirements.
• Institutionalized subjects (e.g., prisons, psychiatric facilities).
• Known history of active coronary artery disease, unstable angina, myocardial infarction, or congestive heart failure present within 6 months or cardiac arrhythmia requiring anti-arrhythmia therapy.
• Known autoimmune disease or presence of autoimmune phenomena (except rheumatoid arthritis requiring only low dose maintenance corticosteroids); or infection requiring intravenous antibiotic use within 1 week.
• Known history of active COPD, or other moderate-to-severe respiratory illness present within 6 months.
• Patients who are diabetic and/or have high blood pressure are at a higher risk for developing late-stage renal failure. While these patients will not be specifically excluded, physician-investigators must carefully discuss the associated late risks to these patients.
• Patients must be at least 4 weeks beyond prior chemotherapy, surgery, radiotherapy to an index lesion, or experimental therapy (i.e., drugs, biologicals, procedures) and meet all eligibility criteria.
• Patients who received a treatment containing a nitrosourea compound will not be enrolled for at least 6 weeks after the end of that treatment.