E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Advanced ovarian cancer patients with recurrent symptomatic malignant ascites. |
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MedDRA Classification |
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 |
•Estimate the repeat paracentesis response rate (RPRR) in advanced ovarian cancer patients with recurrent symptomatic malignant ascites.
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E.2.2 | Secondary objectives of the trial |
•Estimate the general safety and tolerability of AVE0005 (VEGF Trap) in advanced ovarian cancer patients with recurrent symptomatic malignant ascites. •Estimate the effect of AVE0005 (VEGF Trap) treatment on time to repeat paracentesis (TRP) and 60-day frequency of paracentesis (FOP). •Estimates the effect of AVE0005 (VEGF Trap) treatment on progression-free survival (PFS), and overall survival (OS) in advanced ovarian cancer patients with recurrent symptomatic malignant ascites. •Determine if human anti-AVE0005 (VEGF Trap) antibodies develop in advanced ovarian cancer patients with recurrent symptomatic malignant ascites treated with AVE0005 (VEGF Trap). |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Patient is willing and able to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures and agrees to participate in the study by providing written informed consent prior to any study-related requirements. 2. Patient is female ≥18 years of age. 3. Patient has symptomatic malignant ascites resulting from advanced ovarian epithelial cancer (including fallopian tube and primary peritoneal adenocarcinoma) that has required at least 3 previous therapeutic paracenteses at a frequency of 1-4 paracenteses per month for management. 4. Platinum-resistant disease defined by relapse or progression of disease during or after treatment, or drug intolerance. 5. Topotecan- and/or liposomal doxorubicin-resistant disease defined by relapse or progression of disease during or after treatment, or drug intolerance. 6. Patient underwent Day 1 paracentesis for symptoms consistent with abdominal discomfort, bloating, or pain with ≥1 liter of ascitic fluid removed. 7. Patient has an Eastern Cooperative Oncology Group (ECOG) performance status ≤2. 8. Patient is postmenopausal, surgically sterile, or using effective contraception. 9. Patient has adequate organ and bone marrow function as evidenced by: •hemoglobin ≥8.0 g/dL •absolute neutrophil count ≥1.0 x 10 9 /L •platelet count ≥75 x 10 9 /L •creatinine ≤1.5 x ULN, and either proteinuria ≤500 mg/24 hours or urine protein:creatinine ratio (UPCR) ≤1 •AST/SGOT, ALT/SGPT, and total bilirubin ≤2.5 x ULN •international normalized ratio (INR) within normal limits (or ≤1.5 x ULN if on prophylactic anticoagulation) and activated partial thromboplastin time (aPTT) within normal limits. |
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E.4 | Principal exclusion criteria |
1. Patient has pseudomyxoma peritonei or peritoneal mesothelioma. 2. Patient has radiographic evidence of intestinal obstruction (e.g., dilated loops of bowel accompanied by air-fluid levels) requiring surgical intervention or gastrointestinal perforation (e.g., presence of extraluminal gas) requiring surgical intervention. 3. Patient has ascites associated with a non-malignant condition, including but not limited to ascites associated with mechanical obstruction, congestive heart failure, constrictive pericarditis, portal hypertension, hypoproteinemia of hepatic failure or nephrotic syndrome (often associated with serum to ascites albumin gradient >1.1, i.e. transudative ascites). 4. Patient has a peritoneovenous or other type of shunt that was placed for the management of ascites. 5. Anticipation of need for a major surgical procedure or radiation therapy during the study. 6. Likelihood of requiring treatment during the study period with drugs or devices not permitted by the clinical trial protocol. 7. Patient has had any of the following conditions within 6 months prior to study entry: myocardial infarction, severe/unstable angina pectoris, coronary/peripheral artery bypass graft, NYHA class III or IV congestive heart failure, cerebrovascular accident or transient ischemic attack, peptic ulcer disease, erosive esophagitis or gastritis, hepatic cirrhosis, portal venous obstruction, infectious or inflammatory bowel disease, diverticulitis, pulmonary embolism, deep vein thrombosis, or other thromboembolic event. 8. Patient has uncontrolled hypertension (with or without antihypertensive drug treatment), defined as blood pressure >150/100 mm Hg or systolic blood pressure >180 mm Hg on at least 2 repeated determinations on separate days within 3 months prior to study entry. 9. Patient has received tumor-directed immunologic therapy, targeted therapy, radiation therapy, surgery, chemotherapy, or an investigational agent (including FDA approved drugs for a non-FDA approved indication) within 3 weeks prior to study entry. For major surgery, mitomycin or nitrosoureas, there must be a 6-week treatment-free interval. 10. Patient has a known history of hypersensitivity to any Trap agent or recombinant proteins. 11. Patient has been previously treated with AVE0005 (VEGF Trap), bevacizumab, or other inhibitor of VEGF or VEGFR. 12. Patient has a serious, unresolved complication of malignant disease including, but not limited to, untreated superior vena cava syndrome, spinal cord compression, or refractory hypercalcemia of malignancy. 13. Patient has previously known brain metastases, spinal cord compression, carcinomatous meningitis, or new evidence of brain or leptomeningeal disease. 14. Patient has known, clinically significant, active infection or bleeding, or underlying bleeding disorder. 15. Patient has a history of any condition (social or medical) that, in the opinion of the investigator, might confound the results of the study, or pose additional, unacceptable risk to the patient. 16. Patient is pregnant, breastfeeding, planning to become pregnant or unwilling to use effective contraception. 17. Patient is mentally or legally incapacitated (unable to understand the nature, scope and possible consequences of the study) at the time of the study or has been (<1 year prior to study entry) a user of illicit drugs or abuser of alcohol. 18. Patient is unlikely to either comply with the protocol (e.g., uncooperative attitude, inability to return for follow-up visits), or complete the study. 19. Patient has been previously registered in this study. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy endpoint will be repeat paracentesis response (RPR) defined as at least a twofold increase in TRP as compared to the average of the 2 intervals between the 3 most recent paracenteses prior to study registration. TRP will be defined as the number of days between the date of registration and the date of the first post-registration paracentesis. For this endpoint, each patient will be followed for 6 months or until study withdrawal. |
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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 | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Determination of the immunogenicity of IV AVE0005 & physiometric validation of the AIM |
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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 | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Information not present in EudraCT |
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 | Information not present in EudraCT |
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 | No |
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 | 4 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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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 | 1 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |