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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


Phase 1
18 Years
N/A
Not Enrolling
Both
Epithelial Cancer Patients

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Trial Information

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


Epithelial cancer patients who are progressing on or after standard therapy or for whom no
standard therapy exists. Catumaxomab (trifunctional anti-EpCAM x anti-CD3
antibody)Catumaxomab will be administered i.v. once weekly (qwk) with each infusion lasting
for 6 hours. The starting dose for catumaxomab will be 2 µg. The dose escalation schedule is
based on a Modified Fibonacci Schedule with the following dose cohorts: 2 µg, 4 µg, 7 µg, 10
µg, 14 µg and 19 µg qwk corresponding to dose increments of 100%, 75%, 43%, 40% and 36%
respectively of the previous dose. Subsequent dose levels will correspond to dosing
increments of about 30%, e.g. 25, 33, 43, 56 µg. After completion of the DLT period, all
patients will be offered continuation of catumaxomab treatment at the same dose until
disease progression or death, whichever occurs first. The maximum length of treatment,
however, will be restricted to an additional 12 weeks after the DLT period - resulting in a
maximum treatment duration of 16 weeks total.


Inclusion Criteria:



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
exists.

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.

Exclusion Criteria:

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
therapy regimen).

5. Exposure to nitrosoureas or mitomycin C within 6 weeks prior to the first infusion of
catumaxomab.

6. Abnormal organ or bone marrow function as defined below (any single parameter to
fulfill condition):

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
anticoagulant therapy)

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

Type of Study:

Interventional

Study Design:

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Maximal Tolerated Dose

Outcome Time Frame:

The dose escalation schedule is based on a Modified Fibonacci Schedule

Safety Issue:

Yes

Principal Investigator

Josep Tabernero, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Vall d'Hebron University Hospital, Barcelona, Spain

Authority:

Germany: Paul-Ehrlich-Institut

Study ID:

IV-CAT-ST-01

NCT ID:

NCT01320020

Start Date:

February 2011

Completion Date:

March 2013

Related Keywords:

  • Epithelial Cancer Patients
  • Cancer
  • Neoplasm
  • Carcinoma
  • intravenous
  • Monoclonal Antibody
  • Removab

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