E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Advanced epithelial ovarian cancer or primary peritoneal cancer |
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MedDRA Classification |
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 |
• To evaluate the efficacy of volociximab in combination with liposomal doxorubicin in advanced epithelial ovarian cancer or primary peritoneal cancer. • To evaluate the safety and tolerability of volociximab in combination with liposomal doxorubicin. |
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E.2.2 | Secondary objectives of the trial |
• To evaluate the PK of volociximab in combination with liposomal doxorubicin. • To evaluate quality of life (QoL) benefits of volociximab in combination with liposomal doxorubicin. Additional objectives: • To evaluate the pharmacodynamic activity of volociximab through studies of serum protein biomarkers. • To investigate the potential relationship between tumor expression of α5β1 or other relevant biomarkers and clinical response to volociximab. • To measure volociximab and possibly other protein biomarkers in ascitic fluid obtained from subjects in whom paracentesis can be safely performed and investigate potential correlations with clinical response to volociximab. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Must give written informed consent and any authorizations required by local law (e.g., Protected Health Information [PHI]). 2. Females aged ≥18 years old at the time of informed consent. 3. Advanced (Stage III or IV) histologically-documented epithelial ovarian cancer or primary peritoneal cancer (excluding small, round-cell histologies). 4. Recurrent or persistent disease. 5. Received no more than 2 prior cancer treatment regimens, at least one of which must have included a platinum/taxane-based therapy (carboplatinum, cisplatinum, or another organoplatinum compound). If the same regimen is given more than once, it will only count as one regimen. Similarly, if components of a regimen are given more than once using the same schedule, it will only count as one regimen. 6. At least 1 target lesion to assess response by RECIST criteria. (Tumors within a previously irradiated field are designated as non-target.) 7. ECOG Performance Status ≤1. 8. Life expectancy >12 weeks. 9. Available paraffin block or unstained paraffin sections on glass slides containing representative tumor tissue from the most recent tumor biopsy/resection. 10. Subjects of child-bearing potential must be willing to practice effective contraception during the study and be willing and able to continue contraception for at least 6 months after their last dose of study treatment (about 5 half lives). |
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E.4 | Principal exclusion criteria |
1. Clinical laboratory values outside of the following laboratory thresholds: a) Granulocyte count <1500/µL b) Platelet count <75,000/µL c) Hemoglobin <8.5 g/dL (hemoglobin may be supported by transfusion or erythropoietin or other approved hematopoietic growth factors; darbopoeitin [Aranesp®] is permitted) d) Serum bilirubin >2.0 × upper limits of normal (ULN) e) AST and ALT >2.5 × ULN (AST and ALT >5 × ULN for subjects with liver metastasis) f) Serum creatinine >2.0 mg/dL g) International normalized ratio (INR) >1.5 h) Activated partial thromboplastin time (aPTT) >1.5 × ULN 2. Unstable angina or a history of myocardial infarction within 6 months prior to Day 1. 3. New York Heart Association (NYHA) ≥Grade II congestive heart failure. 4. Subjects who have received prior (liposomal) anthracycline or anthracenedione therapy. 5. Any investigational, anti-cancer therapy within 6 weeks prior to Day 1. 6. Any non-investigational, anti-cancer therapy within 4 weeks prior to Day 1. 7. Prior treatment with anti-angiogenic agents. 8. Subjects who are taking concomitant immunomodulatory agents including, but not limited to, interferons, interleukins, systemic steroids, cyclosporine, tacrolimus, calcineurin inhibitors, chronic low-dose methotrexate, or azathioprine. (The use of inhaled or intranasal steroids or oral steroids at a dose of ≤10 mg/day prednisone or its equivalent are permitted.) 9. Subjects who require treatment with an anti-coagulant with the exception of low-dose Aspirin® (≤81 mg/day), warfarin (≤1 mg/day), or heparin for IV catheter patency. 10. Subjects with a left ventricular ejection fraction (LVEF) <50%. 11. History of stroke or transient ischemic attack within 6 months prior to Day 1. 12. Clinically significant peripheral vascular disease. 13. Evidence of bleeding diathesis or coagulopathy. (Note: Prior history of deep vein thrombosis will not exclude subjects from participating in this study.) 14. History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to Day 1. 15. Serious, non-healing wound, ulcer, or bone fracture. 16. Evidence of autoimmune disease including, but not limited to, ulcerative colitis, Crohn’s disease, rheumatoid arthritis, systemic lupus erythematosus, scleroderma, and other disease in which immune function or immune competence is known to be impaired. 17. Active infection requiring systemic antibiotics, antivirals, or antifungals including HIV/AIDS, hepatitis B, or hepatitis C infection. 18. Any history of lymphoproliferative disorder. 19. Known human anti-murine antibody (HAMA) and/or human anti-chimeric antibody (HACA). 20. Known central nervous system or brain metastases. 21. History of other malignancies within 3 years of Day 1, except for adequately treated carcinoma in situ of the cervix, ductal carcinoma in situ (DCIS) of breast, or basal, or squamous cell skin cancer. 22. Pregnant (positive pregnancy test) or lactating. 23. Inability to comply with study and follow-up procedures. 24. Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that in the opinion of the Investigator gives reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the subject at high risk from treatment complications.
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E.5 End points |
E.5.1 | Primary end point(s) |
Progression-free survival |
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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 | Yes |
E.6.13.1 | Other scope of the trial description |
Quality of Life assessment |
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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 | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
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) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
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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 | 19 |
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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End of study is defined as the last treatment or follow up visit of the last subject particpating in the study. |
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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 | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |