A Phase I, Open Label, Dose Escalating Study to Evaluate the Safety and Tolerability of Ascending Intravenous (i.v.) Doses of Catumaxomab in Epithelial Cancer Patients
1. Patients with epithelial cancer known to have EpCAM overexpression in at least 80% of
patients, progressing on or after standard therapy or for whom no standard therapy
2. At least one assessable lesion according to RECIST in at least one dimension on
computed tomography (CT).
3. Life expectancy ≥ 3 months.
4. Age ≥ 18 years.
5. ECOG Performance Status ≤ 1
6. Females of childbearing potential must have a negative serum pregnancy test within 48
hours prior to first infusion of catumaxomab and must use an effective contraception
(intrauterine devices, hormonal contraceptives, contraceptive pill, implants,
transdermal patches, hormonal vaginal devices, injections with prolonged release)
during the study and at least 13 days after participating in the study.
7. Patients capable to understand the purposes and risks of the study, who are willing
and able to participate in the study and from whom written and dated informed consent
to participate in the study has been obtained.
1. Patients with known clinically symptomatic brain metastases.
2. Concomitant cancer chemo- or radiotherapy (except for local radiation therapy for
bone marrow metastasis)
3. Treatment with any investigational product within 4 weeks prior to first
administration of catumaxomab
4. In cases of previous exposure to cancer-, chemo-, immune- or radiotherapy (except for
local radiation therapy for bone marrow metastasis) patients must be excluded if not
sufficiently recovered from previous treatment (toxicity present) based on adequate
laboratory values and general status according to other in/exclusion criteria (i.e.
this might be less than 1 or 2 weeks after a weekly or bi-weekly scheduled previous
5. Exposure to nitrosoureas or mitomycin C within 6 weeks prior to the first infusion of
6. Abnormal organ or bone marrow function as defined below (any single parameter to
6.1. ANC < 1.5 (1.5x109/L, 1500/mm3) 6.2. Hemoglobin < 9.0 g/dL 6.3. Platelet count <
75 (75x109/L, 75,000/mm³) 6.4. AST(SGOT)/ALT(SGPT) > 3 x upper limit of normal (ULN);
6.5. Alkaline phosphatase > 2.5 x ULN 6.6. Serum (total) bilirubin > 1.5 x ULN; 6.7.
Serum creatinine > 1.5 x ULN; 6.8. Serum creatinine > 1.5 x ULN (exception: pts on
7. Use of immune-suppressive agents for the past 4 weeks prior to first administration
of catumaxomab. For regular use of systemic corticosteroids, patients should only be
included after stepwise discontinuation to be free of steroids for a minimum of 5
days prior to first administration of catumaxomab.
8. Any known active or chronic infection.
9. Known infection with human immunodeficiency virus (HIV positive) and/or hepatitis B
virus (HBsAg positive) or hepatitis C virus (anti-HCV positive).
10. Any other concurrent disease or medical conditions that are deemed to interfere with
the conduct of the study as judged by the investigator.
11. Known hypersensitivity to catumaxomab and its analogues in general, or to any other
component of the study drug formulation.
12. Patients with congestive heart failure NYHA Class III and IV. Cardiac arrhythmias
(except atrioventricular block type I and II, atrial fibrillation/flutter, bundle
brunch block) or other signs and symptoms of relevant cardiovascular disease.
13. Pregnant women, nursing mothers, lactating women, and women of child-bearing
potential who are unwilling to use effective contraception (intrauterine devices,
hormonal contraceptives, contraceptive pill, implants, transdermal patches, hormonal
vaginal devices, injections with prolonged release). Effective contraception must be
used for the duration of the study and for at least 13 days after participating in
the study. Effective contraception must be used by men and women for the duration of
the study and for at least 13 days after participating in the study.
14. Unwilling or unable to follow protocol requirements.
15. Patients with a history of liver cirrhosis