This is an international, explorative, open-label, prospective, non-randomized multicenter phase II study to assess the feasibility and clinical activity of initial intraperitoneal catumaxomab followed by chemotherapy regimes in patients with recurrent epithelial ovarian cancer and punctuable ascites. MedDRA version: 15.0 Level: PT Classification code 10066697 Term: Ovarian cancer recurrent System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: Removab 10 microgram
Product Name: catumaxomab (INN)
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: CATUMAXOMAB
CAS Number: 509077-98-9
Concentration unit:
Sponsors
Charité - Universitätsmedizin Berlin
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Histologically or cytologically confirmed diagnosis of epithelial ovarian cancer, primary peritoneal carcinomatosis or fallopian tube cancer 2. Recurrent ovarian cancer disease evaluated by radiographic Response Evaluation Criteria In Solid Tumors (RECIST) criteria or clinically or by CA 125 increase according GCIG-criteria (see below) (maximum 3 recurrences) with current recurrence defined as: progression during platinum-containing therapy or within 6 months after last platinum-containing chemotherapy (platinum resistant or platinum refractory disease) 3. Signs for progression either measurable disease according to radiographic Response Evaluation Criteria In Solid Tumors (RECIST) criteria with documented tumor progression or CA 125 increase according the GCIG-criteria (see below) or clinical symptoms of tumor progression according to RECIST criteria. Note: Signs for progression due to CA 125 increase according the GCIG-criteria must be combined with clinical symptoms or diagnostic imaging 4. Radiological confirmed ascites (including ultrasound), possible to puncture 5. Life expectancy = 12 weeks 6. Age = 18 years 7. ECOG performance status ? 2 8. 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 9. 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 before the start of specific protocol procedures 10. Non-childbearing potential (i.e., physiologically incapable of becoming pregnant), including any female who has had: • A hysterectomy • A bilateral oophorectomy (ovariectomy) • A bilateral tubal ligation • Is post-menopausal • Subjects not using hormone replacement therapy (HRT) must have experienced total cessation of menses for = 1 year and be greater than 45 years in age, OR, in questionable cases, have a follicle stimulating hormone (FSH) value >40 mIU/mL and an estradiol value = 1 year and be greater than 45 years of age OR have had documented evidence of menopause based on FSH and estradiol concentrations prior to initiation of HRT OR Negative serum pregnancy test of women of childbearing potential Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 34 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range 17
Exclusion criteria
Exclusion criteria: 1. Patients with known brain metastases 2. Concomitant cancer, chemo- or radiotherapy (except for local radiation therapy for bone marrow metastases) 3. Treatment with any investigational product within 2 weeks prior to first administration of catumaxomab 4. 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) 5. Patients must not have been exposed to nitrosoureas or mitomycin C within 6 weeks prior the first infusion of catumaxomab 6. Abnormal organ or bone marrow function as defined below: - absolute neutrophil count (ANC) 3 x upper limit of normal (ULN), or > 5 x ULN in cases of metastatic liver disease or alkaline phosphatase (AP) > 2,5 upper limit of normal (ULN) - Serum (total) Bilirubin > 1.5 x ULN or in case of liver metastasis >3 x ULN - Serum creatinine > 1.5 x ULN or = 60 mL calculated according to Cockroft-Gault 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 study entry 8. Any known active and 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 or suspected hypersensitivity to catumaxomab and its analogues in general 12. Known or suspected hypersensitivity to PLD, topotecan, paclitaxel, gemcitabine or their excipients. 13. 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 14. Patients with substance abuse, medical or psychological or social conditions which the investigator believes would preclude compliance with the study requirements. 15. Unwilling or unable to follow protocol requirements 16. Participation in another clinical study with experimental therapy within 14 days before start of treatment 17. Legal incapacity or limited legal capacity 18. Subjects housed in an institution on official or legal orders 19. Pregnancy or lactation period
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Feasibility of close sequential combination of catumaxomab and established chemotherapy regimens defined by rate of patients with at least 4 chemotherapy cycles following catumaxomab-treatment in the scope of this clinical trial.;Secondary Objective: • Overall safety evaluation • Percentage of patients who can receive all 4 application of catumaxomab within 20 days and who are able and committed to receive further mono chemotherapy • Percentage of patients who can start chemotherapy after a maximum of 4-7 days after last catumaxomab application • Percentage of patients with no signs of malignant ascites at time of progression or change of therapeutic strategy • puncture-free interval • time to progression (TTP) • overall response rate (ORR) and duration of response of second or third or fourth line chemotherapy and comparison with historical data • treatment free interval to subsequent therapy • PFS , OS • quality of life over time as defined by EORTC-QLQ C 30 and Ovar 28 questionnaire • Analysis of potential predictive clinical factors for response to catumaxomab (e.g. amount of ascites, histology, relative lymphocyte count) ;Primary end point(s): The primary target value of this study is the feasibility of close sequential combination of catumaxomab and established chemotherapy regimens defined by rate of patients with at least 4 chemotherapy cycles following catumaxomab-treatment in the scope of this clinical trial.;Timepoint(s) of evaluation of this end point: at the end of study | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Overall safety evaluation o occurrence and severity of adverse events (AEs) o number of patients with AEs o occurrence 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 • safety score of catumaxomab* • Percentage of patients who can receive all 4 application of catumaxomab within 20 days and who are able and committed to receive further mono chemotherapy • Percentage of patients who can start chemotherapy after a maximum of 4-7 days after last catumaxomab application • Percentage of patients with no signs of malignant ascites at time of progression or change of therapeutic strategy • To assess puncture-free interval (defined as paracentesis-free interval after last catumaxomab application/ removal of catheter) • To assess time to progression (TTP) according to RECIST and/or CA-125 response rate • To assess the overall response rate (ORR) and duration of resonse (according to RECIST and/or CA-125 response) of second or third or fourth line chemotherapy and compare with historical data • To assess treatment free interval to subsequent therapy (defined as duration of the interval between last chemotherapy application and start of next chemotherapy or start of second cycle) • To assess PFS according to RECIST and/or CA-125 response rate, OS • To assess quality of life over time as defined by EORTC-QLQ C 30 and Ovar 28 questionnaire • Analysis of potential predictive clinical factors for response to catumaxomab (e.g. amount of ascites, histology, relative lymphocyte count) ;Timepoint(s) of evaluation of this end point: at the end of study | — |
Countries
Germany
Contacts
Public ContactStudiensekretariat
Charité Campus Virchow-Klinikum
Outcome results
None listed