E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Platinum-Resistant Advanced Epithelial Ovarian Cancer or Primary Peritoneal Cancer |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10052171 |
E.1.2 | Term | Peritoneal carcinoma |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10061328 |
E.1.2 | Term | Ovarian epithelial cancer |
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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 |
To evaluate the efficacy of volociximab when administered at 15 mg/kg per week in subjects with platinum-resistant, advanced epithelial ovarian cancer or primary peritoneal cancer. |
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E.2.2 | Secondary objectives of the trial |
-To evaluate the safety and tolerability of volociximab when administered at 15mg/kg per week. -To evaluate the pharmacokinetics (PK) of volociximab when administered at 15mg/kg per week -To evaluate the pharmacodynamic activity and mechanism of action of volociximab using multiple biologic assessments including studies of serum and whole blood proteins and cellular biomarkers -To investigate the potential relationship between tumour expressions of alpha5beta1 or other relevant markers and clinical response to volociximab. -To measure the concentration of volociximab and protein markers in ascitic fluid obtained from subjects in whom paracentesis can be safely performed and to evaluate potential correlations with clinical outcomes. |
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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. 2. Females aged at least 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. Radiologically-documented evidence of progressive disease. 5. Platinum-resistant disease defined as having a best response of SD or disease progression during or within 6 months of discontinuing a platinum-based chemotherapy (carboplatinum, cisplatinum, or another organoplatinum compound). 6. Progression during or following treatment with topotecan or liposomal doxorubicin. 7. 3 or fewer prior chemotherapy regimens (including a platinum-based therapy). 8. At least 1 measurable target lesion in accordance with RECIST criteria to assess clinical response (tumors within a previously irradiated field are designated as non-target). 9. ECOG Performance Status < or = 1. 10. Life expectancy >12 weeks. 11. Available paraffin block or unstained paraffin sections on glass slides containing representative tumor tissue from the most recent tumor biopsy/resection. 12. 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). Acceptable methods of contraception include any of the following: oral, depot, or injectable contraceptives; intrauterine devices (IUDs); NuvaRing®; birth control patch, or double-barrier contraception. Double-barrier contraception must consist of 2 of the following: condom, female condom, diaphragm, cap, shield, sponge, spermicide. The only exceptions to contraception are: subject is postmenopausal for at least 1 year before Study Day 1, subject abstains from sexual intercourse, subject or partner is surgically sterile (i.e., no uterus or no ovaries. Note: subjects who have their fallopian tubes ligated are not considered surgically sterile.)
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E.4 | Principal exclusion criteria |
1. Screening clinical laboratory values: a) Absolute neutrophil count <1500/uL b) Platelet count <75,000/uL c) Hemoglobin <8.5 g/dL (hemoglobin may be supported by transfusion, erythropoietin, or other approved hematopoietic growth factors; darbopoeitin [Aranesp®] is permitted) d) Serum bilirubin >2.0 x upper limit of normal (ULN) e) AST and ALT >2.5 x ULN (AST and ALT >5 x 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 x ULN 2. Clinically significant peripheral vascular disease. 3. Non-epithelial ovarian tumors. 4. Active infection requiring systemic antibiotics, antivirals, or antifungals including HIV/AIDS, hepatitis B, or hepatitis C infection. 5. History of abdominal fistula, gastrointestinal (GI) perforation, or intra-abdominal abscess within 6 months prior to Day 1. 6. Serious, non-healing wound, or bone fracture. 7. Known central nervous system or brain metastases. 8. History of uncontrolled psychiatric condition within 6 months prior to Day 1. 9. 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. 10. Evidence of autoimmune disease including, but not limited to, ulcerative colitis, Crohn’s disease, rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) sceloderma, or another diseases in which immune function or immune competence is known to be impaired. 11. Any history of lymphoproliferative disorder. 12. Known human anti-murine antibody (HAMA) and/or human anti-chimeric antibody (HACA). 13. Any medical condition that may be exacerbated by bleeding, including a known bleeding disorder such as a coagulation defect, thrombocytopenia, active gastric or duodenal ulcer, or history of GI bleeding. 14. Significant hemoptysis within one year prior to Study Day 1. 15. Any investigational, anti-cancer therapy within 6 weeks prior to Day 1. 16. Any non-investigational, anti-cancer therapy within 4 weeks prior to Day 1. 17. Prior treatment with anti-angiogenic agents. 18. Subjects who require treatment with an anti-coagulant with the exception of low-dose warfarin (< or = 1 mg/day) or heparin for IV catheter patency. (Note: Acetylsalicylic acid and non-steroidal anti-inflammatory drugs are permitted). 19. 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 < or = 10 mg/day prednisone or its equivalent are permitted.) 20. Active, unstable severe cardiovascular disease, including poorly controlled angina, congestive heart failure (CHF), arrhythmias, myocardial infarction (MI), cardiomyopathy, atrioventricular (AV) block, electrocardiogram (ECG) evidence of acute ischemia, or significant conduction abnormality. 21. History of thromboembolic or cerebrovascular events, such as stroke, or transient ischemic attack (TIA). (Note: Prior history of deep vein thrombosis will not exclude subjects from participating in this study.) 22. Pregnant (positive pregnancy test) or lactating. 23. Inability to comply with study and follow-up procedures. 24. Any condition that, in the opinion of the Investigator, makes the subject unsuitable for study participation. 25. Known hypersensitivity to murine or chimeric antibodies. 26. Major surgery within 4 weeks prior to Day 1. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy endpoint is ORR, defined as the proportion of subjects who have achieved a CR or PR.
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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 | No |
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 | 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 | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
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 | No |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | No |
E.8.5.1 | Number of sites anticipated in the EEA | 1 |
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 | Information not present in EudraCT |
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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When the last subject has completed their end of treatment visit or the last subject has completed 3 months of treatment, whichever occurs first. |
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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 |