E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Advanced or metastatic platinum-resistant ovarian cancer patients who experienced progression or recurrence within 6 months after completion of one or two platinum/paclitaxel regimen |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10057529 |
E.1.2 | Term | Ovarian cancer metastatic |
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 |
To compare progression-free survival (PFS) in patients randomized to NGR-hTNF plus an anthracycline versus patients randomized to an anthracycline alone |
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E.2.2 | Secondary objectives of the trial |
• To compare overall survival (OS)
• To compare response rate (RR)
• To compare disease control rate (DCR)
• To compare duration of disease control
• To evaluate safety/toxicity profile related to NGR-hTNF
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Age ≥ 18 years
2. Histologically-proven ovarian cancer, fallopian tube and primary peritoneal cancer in advanced or metastatic stage
3. Patients previously treated with a maximum of two platinum-based regimen (cisplatin or carboplatin) plus paclitaxel and with documented progressive disease on treatment (refractory patient population) or within 6 months from last chemotherapy cycle (resistant patient population)
4. ECOG Performance status 0 - 2 (Appendix A)
5. Life expectancy of 12 weeks or more
6. Normal cardiac function (LVEF ≥ 50%) and absence of uncontrolled hypertension
7. Adequate baseline bone marrow, hepatic and renal function, defined as follows:
a. Neutrophils ≥ 1.5 x 109/L; platelets ≥ 100 x 109/L; hemoglobin ≥ 9 g/dL
b. Bilirubin ≤ 1.5 x ULN
c. AST and/or ALT ≤ 2.5 x ULN in absence of liver metastasis or ≤ 5 x ULN in presence of liver metastasis
d. Serum creatinine < 1.5 x ULN
8. At least one (not previously irradiated) target lesion that could be measured in one dimension, or non-measurable disease only, according to RECIST criteria
9. Patients may have had prior therapy providing the following conditions are met:
a. Surgery and radiation therapy: wash-out period of 14 days
b. Systemic anti-tumor therapy: wash-out period of 21 days
10. Patients must give written informed consent to participate in the study
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E.4 | Principal exclusion criteria |
1. Patients must not receive any other investigational agents while on study
2. More than two previous chemotherapy lines and previous treatment with anthracycline
3. Patients with myocardial infarction within the last six months, unstable angina, New York Heart Association (NYHA) grade II or greater congestive heart failure, or serious cardiac arrhythmia requiring medication
4. Prolonged QTc interval (congenital or acquired) > 450 ms
5. History or evidence upon physical examination of CNS disease unless adequately treated (e.g., primary brain tumor, any brain metastasis, seizure not controlled with standard medical therapy or history of stroke)
6. Patients with active or uncontrolled systemic disease/infections or with serious illness or medical conditions, which is incompatible with the protocol
7. Known hypersensitivity/allergic reaction or contraindications to human albumin preparations or to any of the excipients
8. Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol
9. Pregnancy or lactation.
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E.5 End points |
E.5.1 | Primary end point(s) |
To compare progression-free survival (PFS) in patients randomized to NGR-hTNF plus an
anthracycline versus patients randomized to an anthracycline alone |
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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) |
-To compare overall survival (OS)
-To compare response rate (RR)
-To compare disease control rate (DCR)
-To compare duration of disease control
-To evaluate safety/toxicity profile related to NGR-hTNF |
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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 | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | No |
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 | Yes |
E.6.13.1 | Other scope of the trial description |
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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) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
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 | 8 |
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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The study completion is defined as the date of the close-out visit of the last center, on the condition that all the data have been validated and reassessed the study documents |
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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 | 0 |
E.8.9.1 | In the Member State concerned days | |
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 | 0 |