Feasibility and Clinical Activity of Initial Intraperitoneal Catumaxomab Followed by Chemotherapy in Patients With Recurrent Ovarian Cancer

Study Overview
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Brief Summary
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Single -arm, multicenter phase-II trial for catumaxomab and chemotherapy in patients with recurrent ovarian cancer to investigate the feasibility and clinical activity of initial intraperitoneal catumaxomab followed by chemotherapy regimes.

Official Title
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Single -Arm, Multicenter Phase-II Trial for Catumaxomab and Chemotherapy in Patients With Recurrent Ovarian Cancer to Investigate the Feasibility and Clinical Activity of Initial Intraperitoneal Catumaxomab Followed by Chemotherapy Regimes

Conditions
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Recurrent Epithelial Ovarian Cancer

Intervention / Treatment
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* Drug: Catumaxomab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically or cytologically confirmed epithelial ovarian cancer, primary peritoneal carcinomatosis or fallopian tube cancer Recurrent ovarian cancer disease Signs for progression either measurable disease according to RECIST or CA 125 increase according the GCIG-criteria or clinical symptoms of tumor progression according to RECIST Radiologically and cytologically confirmed malignant ascites possible to puncture Life expectancy ≥ 12 weeks Age ≥ 18 years ECOG performance status at least 1 No prior operation or, in case of prior operation, the patient must be recovered therefrom. The operation must be performed at least 4 weeks prior to start of study drug Capable of understanding the purposes and risks of the study, willing and able to participate in the study, and written informed consent Non-childbearing potential or negative pregnancy test Exclusion Criteria: known brain metastases Concomitant cancer, chemo- or radiotherapy (except for local radiation therapy for bone marrow metastases) Any investigational product within 2 weeks prior to first administration of catumaxomab In cases of previous exposure to investigational product, cancer-, chemo-, immune- or radiotherapy (except for local radiation therapy for bone marrow metastasis): 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) Patients must not have been exposed to nitrosoureas or mitomycin C within 6 weeks prior the first infusion of catumaxomab Abnormal organ or bone marrow function 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 study entry Any known active and chronic infection Known HIV infection and / or hepatitis B virus or hepatitis C virus Any other concurrent disease or medical conditions that are deemed to interfere with the conduct of the study as judged by the investigator Known or suspected hypersensitivity to catumaxomab and its analogues in general or to murine proteins (from rat or mouse) Known or suspected hypersensitivity to PLD, topotecan, paclitaxel, gemcitabine or their excipients. Patients with congestive heart failure New York Heart Association (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 Body mass index (BMI) < 17 (assessment after ascites drainage) Inadequate respiratory function in the opinion of the investigator Presence of complete bowel obstruction Patients with substance abuse, medical or psychological or social conditions which the investigator believes would preclude compliance with the study requirements. Unwilling or unable to follow protocol requirements Participation in another clinical study with experimental therapy within 14 days before start of treatment Legal incapacity or limited legal capacity Subjects housed in an institution on official or legal orders Pregnancy or lactation period

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Catumaxomab<br>Catumaxomab treatment followed by an established chemotherapy regimen | Drug: Catumaxomab<br>* Catumaxomab dosing comprises the following four intraperitoneal (i.p.) infusions via an i.p.-port or an indwelling catheter: 10 µg on day 0 20 µg on day 3 50 µg on day 7 150 µg on day 10<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Feasibility of close sequential combination of catumaxomab and established chemotherapy regimens | Feasibility of close sequential combination of catumaxomab and established chemotherapy regimens defined by rate of patients with at least 4 chemotherapy cycles following 4 applications of catumaxomab within 20 days as described in the scope of this clinical trial. | Approximately 5 months after start of treatment per patient | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number and severity of adverse events as a measure of safety and tolerability | Overall safety evaluation, including cytokine related toxicities (safety score catumaxomab number and severity of adverse events number of patients with AEs occurrence of cytokine release related symptoms hospitalization frequency and duration changes in clinically relevant laboratory values (hematology, clinical chemistry, coagulation, and urinalysis) | Approximately 2.5 years after start of study | 
| Percentage of patients who can receive all 4 applications of catumaxomab within 20 days and who are able and committed to receive further mono chemotherapy | Percentage of patients who can receive all 4 applications of catumaxomab within 20 days and who are able and committed to receive further mono chemotherapy | Approximately 2.5 years after start of study | 
| Percentage of patients who can start chemotherapy after a maximum of 4-7 days after last catumaxomab application | Percentage of patients who can start chemotherapy after a maximum of 4-7 days after last catumaxomab application | Approximately 2.5 years after start of study | 
| Percentage of patients with no signs of malignant ascites at time of progression or change of therapeutic strategy | Percentage of patients with no signs of malignant ascites at time of progression or change of therapeutic strategy | Approximately 2.5 years after start of study | 
| Puncture-free interval (defined as paracentesis-free interval after last catumaxomab application/ removal of catheter) | Puncture-free interval (defined as paracentesis-free interval after last catumaxomab application/ removal of catheter) | Approximately 2.5 years after start of study | 
| Time to progression (TTP) according to RECIST and/or CA-125 response rate | Time to progression (TTP) according to RECIST and/or CA-125 response rate | Approximately 2.5 years after start of study | 
| Overall response rate (ORR) defined as patients with complete or partial response and duration of response (according to RECIST and/or CA-125 response) | Overall response rate (ORR) and duration of response (according to RECIST and/or CA-125 response) of second or third or fourth line chemotherapy and compare with historical data | Approximately 2.5 years after start of study | 
| To assess treatment free interval to subsequent therapy (defined as duration of the interval between last chemotherapy application and start of next chemotherapy | To assess treatment free interval to subsequent therapy (defined as duration of the interval between last chemotherapy application and start of next chemotherapy | Approximately 2.5 years after start of study | 
| To assess PFS according to RECIST and/or CA-125 response rate, OS | To assess PFS according to RECIST and/or CA-125 response rate, OS | Approximately 2.5 years after start of study | 
| To assess quality of life over time as defined by EORTC-QLQ C 30 and Ovar 28 questionnaire | To assess quality of life over time as defined by EORTC-QLQ C 30 and Ovar 28 questionnaire | Approximately 2.5 years after start of study | 
| Potential predictive clinical factors for response to catumaxomab | Analysis of potential predictive clinical factors for response to catumaxomab (e.g. amount of ascites, histology, relative lymphocyte count) | Approximately 2.5 years after start of study | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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recurrent epithelial ovarian cancer