A Open Label, Dose Escalating Study to Evaluate the Safety and Tolerability of Ascending Intravenous (i.v.) Doses of Catumaxomab in Epithelial Cancer Patients

NCT ID: NCT01320020

Last Updated: 2013-07-02

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 16 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-02-28
• Study Completion Date: 2013-03-31

Brief Summary

The study is designed as an open-label dose-escalation study to investigate the safety and tolerability of catumaxomab qwk in patients with epithelial cancer. The treatment period for dose escalation (dose limiting toxicity (DLT) period) consists of 4 weeks, comprising 4 single i.v. administrations of catumaxomab followed by 1 week for safety observations after each administration. All patients will be offered continuation of catumaxomab treatment at the same dose until disease progression or death, whichever occurs first.

Detailed Description

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.

Conditions

Epithelial Cancer Patients

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

catumaxomab

Group Type: EXPERIMENTAL

catumaxomab

Intervention Type: DRUG

Inter patient dose escalation 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

Interventions

catumaxomab

Inter patient dose escalation 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

Intervention Type: DRUG

Eligibility Criteria

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

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Neovii Biotech

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Josep Tabernero, MD

Role: STUDY_CHAIR

Vall d'Hebron University Hospital, Barcelona, Spain

Christian Dittrich, Prim.Univ.-Prof.

Role: PRINCIPAL_INVESTIGATOR

Zentrum für Onkologie und Hämatologie, Kaiser Franz Josef-Spital, Wien, Austria

Morten Sorenesen, MD, Ph.D.

Role: PRINCIPAL_INVESTIGATOR

The Finsen Center, Department of Oncology, Rigshospitalet, Copenhagen, Denmark

Locations

Prof. Christian Dittrich

Vienna, , Austria

Dr. Morten Soerensen

Copenhagen, , Denmark

Dr. Josep Tabernero

Barcelona, , Spain

Countries

Austria; Denmark; Spain

Other Identifiers

IV-CAT-ST-01

Identifier Type: -

Identifier Source: org_study_id