Condition category
Cancer
Date applied
04/09/2011
Date assigned
28/10/2011
Last edited
05/11/2012
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Lay summary under review 2

Trial website

Contact information

Type

Scientific

Primary contact

Dr Michael Ströhlein

ORCID ID

Contact details

Clinic for Visceral
Vascular and Transplant Surgery
The Department of Surgery
University of Witten / Herdecke
Campus Köln-Merheim
Ostmerheimer Str. 200
Cologne
51109
Germany
+49-221-8907-3770
stroehleinm@kliniken-koeln.de

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

10-022810-26

Study information

Scientific title

Multicentre, open-label phase II study to evaluate the efficacy of a two cycle immunotherapy with the trifunctional bispecific antibody catumaxomab (anti EpCAM x anti-CD3) in addition to systemic chemotherapy in patients with peritoneal carcinomatosis from gastric or colorectal adenocarcinoma

Acronym

Study hypothesis

The main hypothesis is that a two cycle intraperitoneal (i.p.) catumaxomab treatment in addition to “standard” intravenous (i.v.) chemotherapy is able to increase symptom and progression free survival in patients with peritoneal carcinomatosis of gastric or colorectal origin not eligible for cytoreductive surgery or with no chance to obtain macroscopic complete cytoreduction. According to the primary endpoints this is defined as:
1. Decrease of the incidence of clinically significant malignant ascites
2. Decrease of the Incidence of intestinal obstruction with the need of surgical intervention or parenteral nutrition
3. Decrease of the incidence of Eastern Cooperative Oncology Group (ECOG) deterioration
4. Decrease of the incidence of death
Every parameter will be analysed separately in comparison to historical controls.

In addition a comprehensive immunological monitoring programme is an integrated part of this study. This programme especially focuses on investigations of the induction of anti tumour responses caused by the i.p. immunotherapy with catumaxomab.

Safety parameters like the need to discontinue catumaxomab infusion as well as frequency, relationship and intensity of clinically relevant grade III and IV adverse events will be documented and analysed.

Ethics approval

1. Ethics Committee of Witten/Herdecke University [Ethikkommission der Universität Wittten/Herdecke, D-59448 Witten], 16 March 2011 ref: F-82/10
2. German Federal Institute for Vaccines and Biomedicines, Paul-Ehrlich-Institut, 24 February 2011, ref: 1220/01)

Study design

Phase II interventional multicentre open-label non-randomized single arm study in comparison to historical controls

Primary study design

Interventional

Secondary study design

Non randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

Peritoneal carcinomatosis from colorectal and gastric cancer (adenocarcinoma)

Intervention

Investigational medicinal product: trifunctional antibody catumaxomab (anti-EpCAM x anti-CD3)
Application of medicinal product: intraperitoneal (i.p.)

Intervention: Laparoscopy or laparotomy and exact staging of peritoneal carcinomatosis will be mandatory. Implantation of an i.p.-port or a catheter-device will be performed. Patients with laparoscopy can be treated with the first dose of catumaxomab after 3 days. Patients with tumor debulking surgery or major resection (anterior rectum resection, gastrectomy) can also be included. In this case, treatment starts at least 10 days after surgery. Further criteria for treatment include complete enteral nutrition and no postoperative problems (i.e. anastomotic leakage, abscess formation etc.). The 1st cycle of catumaxomab is completed by 10-20-50-200 µg on day 0-3-7-10 after start of treatment. Catumaxomab treatment is followed by intravenous chemotherapy within day 30 to 90. A regimen of oxaliplatin, leucovorin, and 5-fluorouracil (FOLFOX4, FOLFOX6, or FOLFIRI) for colorectal and fluorouracil, leucovorin, oxaliplatin (FLO) or fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) for gastric cancer is recommended, but any other chemotherapy according to previous chemotherapy and decision of the medical oncologist is allowed. This is followed by a second cycle of catumaxomab i.p. immunotherapy between day 91 and 120; followed by another i.v.-chemotherapy between day 121 and day 180. Multimodal chemotherapy including biological modifiers (i.e. Cetuximab, Bevacizumab, Trastuzumab or others) is not permitted.

Intervention type

Drug

Phase

Phase II

Drug names

Catumaxomab

Primary outcome measures

1. Decrease of the incidence of clinically significant malignant ascites
2. Decrease of the Incidence of intestinal obstruction with the need of surgical intervention or parenteral nutrition
3. Decrease of the incidence of ECOG deterioration
4. Decrease of the incidence of death
5. Every parameter will be analysed separately in comparison to historical controls

Secondary outcome measures

1. Safety parameters:
1.1. The need to discontinue catumaxomab infusion
1.2. Frequency, relationship and intensity of clinically relevant grade III and IV adverse events
2. Immunological monitoring:
2.1. Induction of anti-tumour response
2.2. Quality and quantity of epithelial cell adhesion molecule (EpCAM)-expression
2.3. Disseminated tumour cells and tumour stem cells within the peripheral blood during therapy
2.4. Anti-EpCAM and anti-HER2/neu humoral immune response
2.5. vascular endothelial growth factor (VEGF)-level during therapy
2.6. Induction of human anti-mouse antibodies (HAMA)
2.7. Systemic levels of catumaxomab after i.p. therapy

Overall trial start date

01/10/2011

Overall trial end date

30/09/2013

Reason abandoned

Eligibility

Participant inclusion criteria

1. Male or female patient aged 18 years or older
2. Signed and dated informed consent
3. Patient has peritoneal carcinomatosis of colorectal or gastric adeno-carcinoma (histologically confirmed)
4. Eastern Cooperative Oncology Group (ECOG) status 1 or 2 (Karnofsky index >= 70)

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

40

Participant exclusion criteria

1. Symptomatic ascites (estimated accululation of more than 1500 ml by sonography and computer tomography and puncture of more than 1500 ml)
2. Ileus or abdominal obstruction with the need of surgical intervention at inclusion or parenteral feeding (> 30% of daily calorie intake)
3. Previous use of non-humanised monoclonal mouse or rat antibodies
4. Known or suspected hypersensitivity or allergy to catumaxomab or to similar antibodies
5. Presence of any acute or chronic systemic infection
6. Pre-existing heart failure > New York Heart Association (NYHA) class II
7. Pregnancy or breast feeding
8. Other concurrent uncontrolled medical conditions
9. Previous Catumaxomab therapy
10. Medical or psychiatric conditions that compromise the patient’s ability to give informed consent
11. Inadequate renal function (Creatinine > 1,5 x ULN)
12. Inadequate hepatic function (AST or ALT > 2.5 x ULN or Bilirubin > 2 x ULN)
13. Inadequate bone marrow function with platelets < 100 000 cells/mm3 or absolute neutrophil count (ANC) < 1500 cells/mm3 or a proportion of < 15% of lymphocytes in differential blood count
14. Pregnant or nursing woman, or woman of childbearing potential who is not using an effective contraceptive method during the study and at least three months after the last infusion (i.e., oral or injectable contraceptives, intrauterine devices, double-barrier method, contraceptive patch, male partner sterilization or condoms)
15. Any further condition which according to the investigator results in an undue risk to the patient during participation in the present study
16. Parallel participation in another clinical trial or previously in this study
17. Treatment with another investigational product during this study or during the last 30 days prior to study start (day 0)
18. Under no circumstances must a patient be enrolled in this study more than once

Recruitment start date

01/10/2011

Recruitment end date

30/09/2013

Locations

Countries of recruitment

Germany

Trial participating centre

Clinic for Visceral, Vascular and Transplant Surgery
Cologne
51109
Germany

Sponsor information

Organisation

University of Witten / Herdecke (Germany)

Sponsor details

c/o Prof Markus M Heiss
Clinic for Visceral
Vascular and Transplant Surgery
The Department of Surgery
Campus Köln-Merheim
Ostmerheimer Str. 200
Cologne
51109
Germany

Sponsor type

University/education

Website

http://www.uni-wh.de

Funders

Funder type

Industry

Funder name

Fresenius Biotech GmbH (Germany)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes