E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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. |
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E.1.1.1 | Medical condition in easily understood language |
patients with recurrent epithelial ovarian cancer and punctuable ascites |
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E.1.1.2 | Therapeutic area | Diseases [C] - Female diseases of the urinary and reproductive systems and pregancy complications [C13] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 15.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10066697 |
E.1.2 | Term | Ovarian cancer recurrent |
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 | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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. |
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E.2.2 | Secondary objectives of the trial |
• 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)
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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 < 40pg/mL (<140 pmol/L). • Subjects using HRT must have experienced total cessation of menses for >= 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 |
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E.4 | Principal 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) < 1500 Gpt /l (1,5x 10 9/L, 1500/mm3) - hemoglobin ≤ 9 g/dL - platelet count < 75 Gpt/L (< 75 x 109/L, 75,000/mm3) - Aspartate aminotransferase (AST/SGOT), alanine aminotransferase (ALT /SGPT), > 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
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E.5 End points |
E.5.1 | 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. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | 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)
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | 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 | Yes |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 6 |
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 | 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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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 | 9 |
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 | 9 |
E.8.9.2 | In all countries concerned by the trial days | 0 |