E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
Accumulation of fluid in the peritoneal cavity due to various cancer types |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10025538 |
E.1.2 | Term | Malignant ascites |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective of the study is to evaluate the safety of a second 3 hour i.p. infusion cycle, consisting of four ascending dosages of catumaxomab after completing four i.p. infusions in the CASIMAS study, in patients with malignant ascites due to carcinoma requiring their first therapeutic puncture. |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives of the study are to determine additional safety parameters, efficacy, quality of life, ascites-related symptom score, catheter handling, as well as the pharmacokinetic and pharmacodynamics of a second i.p. infusion cycle with catumaxomab. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Patients will be enrolled in this study only if they meet all of the following criteria: • Patients capable of understanding 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 • Patients who have completed 4 infusions of catumaxomab in the CASIMAS study. • Age: ≥ 18 years • Karnofsky index ≥ 60% • Patients with malignant ascites requiring their first therapeutic ascites paracentesis after at least 60 days following last catumaxomab infusion in the CASIMAS study. • Patients where standard therapy is either not available or no longer feasible • Body mass index (BMI) between 17 and 40 kg/m2; prior to calculation of BMI reduce ‘body weight’ by weight of current estimated ascites volume (exploratory value is sufficient).
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E.4 | Principal exclusion criteria |
Patients will not be enrolled in this study if they meet any of the following criteria: • Documented acute or chronic infection • Concomitant treatment with investigational products other than catumaxomab, cancer, chemo-, or radiotherapy • In cases of previous exposure to investigational product other than catumaxomab, cancer, chemo- 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. exclusion if less than 1 or 2 weeks after a weekly or bi-weekly scheduled previous therapy regimen). Patients must not have been exposed to nitrosoureas or mitomycin C within 6 weeks prior to the first infusion of catumaxomab. • Previous treatment with entirely murine monoclonal antibodies other than catumaxomab • Known or suspected hypersensitivity to catumaxomab or similar antibodies • Inadequate respiratory function, including symptomatic pleural effusion, distant metastases other than peritoneal carcinomatosis that lead to significant and/or life threatening respiratory distress and dyspnea at rest due to complications of advanced malignancy or other disease, or patients requiring supportive oxygen therapy • Inadequate renal function (creatinine > 1.5 x upper limit of normal [ULN] or GFR (Glomerular filtration rate) < 75% of LLN) • Inadequate hepatic function (aspartate aminotransferase [AST] > 5 x ULN; alanine aminotransferase [ALT] > 5 x ULN; bilirubin > 1.5 x ULN) • Platelets < 80,000 cells/mm3; absolute neutrophil count (ANC) < 1,500 cells/mm3 • Albumin lower than 3 g/dL or total protein lower than 6 g/dL • Partial thromboplastin time (PTT) > 2 x ULN • Hemoglobin < 8 g/dL • Patients requiring entirely parenteral nutrition • Patients with ileus or with symptomatic subileus within the last 30 days • Signs or symptoms of relevant cardiovascular disease, congestive heart failure or cardiac arrhythmias (New York Heart Association [NYHA] class > II) • Liver metastases with volume > 70% of liver metastasized tissue • Known portal vein obstruction • Known brain metastases • Unable or unwilling to comply fully with the protocol • Patients with medical or psychological conditions, which the investigator believes would preclude compliance with the study requirements • Pregnant women, nursing mothers, lactating women, and men or women of child bearing potential who are unwilling to use reliable contraception (hormonal birth control methods including oral contraceptives and contraceptive implants or a barrier method of contraception such as male or female condom, diaphragm, cervical cap plus a spermicide). Effective contraception must be used for the duration of the study and for 6 weeks following completion of the study • Patients with any other severe disease that would render a participation in the study an undue risk according to judgment of investigator. • Patients put into an institution by the authorities of judicial court. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is the proportion of patients who are able to receive a second cycle of at least 3 i.p. infusions of catumaxomab. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Primary endpoint: up to and including i.p. infusion 3 at Day 7 |
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E.5.2 | Secondary end point(s) |
Safety endpoints: • Composite safety score of 3 hours i.p. infusion of catumaxomab, composed of the main known adverse events (AEs) caused by catumaxomab: fever, nausea, vomiting, and abdominal pain. The score after the first treatment cycle in the CASIMAS study will be compared intra-individually with the score after the second treatment cycle in Study IP-CAT-AC-04 for both treatment groups • The aggregated safety profile in Study IP CAT AC-04 will be compared with the aggregated safety profile of the non prednisolone arm in the CASIMAS study. Analyses will include: o incidence and severity of AEs o number of patients with AEs o incidence of cytokine release related symptoms o hospitalization (frequency and duration) o changes in clinically relevant laboratory values (hematology, clinical chemistry, coagulation, and urinalysis) o physical examination o vital signs o correlation between composite safety score and human anti-mouse antibody (HAMA) development during the second treatment cycle. Efficacy endpoints: • Puncture-free survival • Time to next therapeutic ascites puncture • Number of ascites punctures • Overall survival Additional parameters: • Anti-cancer treatment (type, no. of treatments) • Immunomonitoring (tumor cell count, anti-EpCAM and anti HER2/neu levels, absolute immune cell count in peripheral blood) • Quality of Life (standardized 5-dimensional test for health outcome measurements of the EuroQOL group [EQ-5D]) • Ascites-related symptoms (Functional Assessment of Chronic Illness Therapy - Ascites Index, [FACIT-AI]) • Handling of catheter • HAMA development during the first treatment cycle in the CASIMAS study will be compared to HAMA development during the second treatment cycle in Study IP CAT AC 04 • Pharmacokinetics and anti-drug antibodies (ADAs). Catumaxomab concentrations in plasma and ascites will be compared to respective data of the CASIMAS study.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Safety: AEs, incidence CRRS and hospital. until death/6 mon. after treatment start last patient. Physical exam., vital signs, lab. val. until EoS/at puncture visit. Comp. safety score up to EOS, HAMA at Screening/Day 0, until EoS and at puncture visit. Efficacy: PFS = time from puncture at Screening/Day 0 to next punct. Time to/number of asc. punct./OS until death or 6 mon. after treatm. start last pat. Add. param: Anti-cancer treatment until death or 6 mon. after last pat. started treatment. Immunomonitoring at Screening and during treatment period. QoL and Ascites related symptoms: Screening, treatment period and puncture visit. HAMA prior to infusion, treatment period and puncture visit. PK/ADAs: before first inf., during treatment period until 24 h after last inf. |
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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 | Yes |
E.6.7 | Pharmacodynamic | Yes |
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 | No |
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 | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
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 | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
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 | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 15 |
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 | No |
E.8.7 | Trial has a data monitoring committee | Yes |
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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 1 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 1 |
E.8.9.2 | In all countries concerned by the trial days | 0 |