Pretargeted Radioimmunotherapy of Colorectal Cancer: A Phase I Study to Determine Dose-limiting Toxicity and Maximum Tolerated Dose of an Anti-CEACAM5 bsMAb-pretargeted 90Y-hapten-peptide
- Male or female patients, >18 years of age.
- documented histologic or cytologic diagnosis of metastatic (Stage IV) colorectal
- 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
- 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
- Patients able to understand and give written informed consent. Informed consent must
be obtained prior to baseline studies for enrollment purposes.
- 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.,
- 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
- Patients who are, in the opinion of the investigator, unable to comply with the
- 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
- 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.