E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
PERITONEAL CARCINOMATOSIS FROM GASTRIC OR COLORECTAL ADENOCARCINOMA |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10068069 |
E.1.2 | Term | Peritoneal carcinomatosis |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10052360 |
E.1.2 | Term | Colorectal adenocarcinoma |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10017758 |
E.1.2 | Term | Gastric cancer |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
• Decrease of the incidence of clinically significant malignant ascites (defined by one paracentesis of > 1500 ml or a cumulative amount of 1500 ml by multiple paracentesis within 10 days) from 40% (estimated value from the literature) to 15% within 9 months after first catumaxomab therapy. The event will be counted on the day of 2nd paracentesis
• Decrease of the incidence of intestinal obstruction with the indication of surgery or parenteral nutrition (> 14 days, > 70% of calorie intake) from to 40% (estimated value from literature and local database) to 20 % within 9 months after first Catumaxomab therapy
• Decrease of the incidence of ECOG deterioration from ECOG 1 or 2 to ECOG 3 in within 9 months after first Catumaxomab therapy
• decrease of the incidence of death from 60 % to 35% within 9 months after first Catumaxomab therapy
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E.2.2 | Secondary objectives of the trial |
Safety endpoints:
- medical incidence to terminate catumaxomab infusion - Frequency, relationship and intensity of clinically relevant grade III and IV adverse events (AEs)
Immunological endpoints: − Quality and Quantity of EpCAM-expression on PC samples − Incidence and quality of EpCAM positive Tumor cells in intraperitoneal lavage specimen − Disseminated tumor cells and tumor stem cells in peripheral blood during therapy − Proportion and absolute numbers of leukocytes (T-cells, B-cells, NK cells, macrophages) in peripheral blood − Anti-EpCAM and anti-HER2/neu humoral immune response − VEGF levels during therapy − Induction of human anti-mouse antibodies (HAMA) − Pharmakokinetics: Systemic levels of catumaxomab after i.p. therapy − − Blood samples and tissue samples will be asservated for future anaylsis. Informed consent for storage of the samples will be mandatorily obtained from every involved patient.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Signed and dated informed consent • Age 18 years • Patient is suffering from EPCAM-positive peritoneal carcinoma-tosis of colorectal or gastric adenocarcinoma, which was con-firmed by histological analysis. • ECOG status 1 or 2 (Karnofsky index 70) • Patient is not eligible for surgical cytoreduction followed by hy-perthermic intraperitoneal chemotherapy (see Attachments for selection criteria). • Patient is eligible for FOLFOX or FOLFIRI treatment in case of colorectal cancer; patient is eligible for FLO or FLOT treatment in case of gastric cancer (i.e. no intolerance or hypersensitivity, no tumor progression during treatment) • Body mass index > 17 |
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E.4 | Principal exclusion criteria |
• Symptomatic ascites (estimated accumulation of more than 1500 ml by sonography and computer tomography and punc-ture of more than 1500 ml) • Ileus or abdominal obstruction with the need of surgical inter-vention at inclusion or parenteral feeding (> 30% of daily calo-rie intake) • Previous use of non-humanized monoclonal mouse or rat anti-bodies • Known or suspected hypersensitivity or allergy to Catu-maxomab or to similar antibodies • Presence of any acute or chronic systemic infection • Pre-existing heart failure: NYHA class > II • Pregnancy or breast feeding • Other concurrent uncontrolled medical conditions • Previous Catumaxomab therapy • Medical or psychiatric conditions that compromise the patient’s ability to give informed consent • Inadequate renal function (Creatinine >1,5 x ULN) • (PTT) Partial thromboplastine time > x ULN • Inadequate hepatic function (AST or ALT > 2.5 x ULN or Bilirubin > 2 x ULN) • 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 • Pregnant or nursing women, or women of childbearing potential who are 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) • Any further condition which, according to the investigator, re-sults in an undue risk to the patient during participation in the present study • Parallel participation in another clinical trial • Previous participation in the present study • Treatment with another investigational product during this study or during the last 30 days prior to study start (day 0)
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E.5 End points |
E.5.1 | Primary end point(s) |
Symptom- and progression free survival, defined by the primary end-points:
• Incidence of clinically significant malignant ascites (defined by one paracentesis of > 1500 ml or a cumulative amount of 1500 ml by multiple paracentesises within 10 days) • Incidence of intestinal obstruction with the need of surgical in-tervention or parenteral nutrition (>14 days, > 70% of calorie intake) • Increase from ECOG 1 or 2 to ECOG 3 • Death
Each parameter will be analyzed separately with reference to previous patient data. The first day of cumulative ascites paracentesis or intestinal obstruction and parenteral nutrition will be assessed.
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
Control: Historical Data from patients treated traditionally |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
Control: Historical Data from patients treated traditionally |
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E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 7 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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EOT is defined as Dday 270. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |