E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
FIGO Stage III-IV Epithelial Ovarian, Primary Peritoneal or Fallopian Tube Cancers |
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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 | 16.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10061269 |
E.1.2 | Term | Malignant peritoneal neoplasm |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 16.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10016180 |
E.1.2 | Term | Fallopian tube cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 16.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10033128 |
E.1.2 | Term | Ovarian cancer |
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 | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To determine if 6 cycles of paclitaxel and carboplatin plus AMG 386 followed by 18 months of AMG 386 maintenance improves overall survival (OS) compared to
6 cycles of paclitaxel and carboplatin plus AMG 386 placebo followed by 18 months of AMG 386 placebo maintenance |
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E.2.2 | Secondary objectives of the trial |
To evaluate the effect of AMG 386 plus paclitaxel and carboplatin compared to paclitaxel and carboplatin on overall survival (OS) |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Female subjects 18 years of age or older with FIGO Stages III-IV epithelial ovarian, primary peritoneal or fallopian tube cancer with an indication for first-line treatment with paclitaxel and carboplatin x 6 cycles (subjects with pseudomyxoma, mesothelioma, adenocarcinoma with unknown primary tumour, carcinosarcoma, sarcoma, mucinous or neuroendocrine histology are excluded)
Subjects with FIGO Stage IIIA or IIIB disease must have undergone PDS for ovarian, primary peritoneal or fallopian tube cancer within 12 weeks prior to randomization
Subjects with FIGO Stage IIIc or IV disease must either:
- undergo PDS for epithelial ovarian, primary peritoneal or fallopian tube cancer within 12 weeks prior to randomization
or
- plan to have IDS following 3 cycles of paclitaxel and carboplatin plus AMG 386 or AMG 386 placebo for biopsy proven epithelial ovarian, primary peritoneal or fallopian tube cancer
ECOG performance status os 0 or 1
Adequate bone marrow, renal and hepatic funtion |
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E.4 | Principal exclusion criteria |
Prior use of any anticancer therapy or experimental therapy for epithelial ovarian, primary peritoneal or fallopian tube cancers
Previous abdonimal and/or pelvic external beam radiotherapy
History of central nervous metastasis
History of arterial or venous thromboembolism within 12 months prior to randomization
Clinically significant cardiovascular disease within 12 months prior to randomization |
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E.5 End points |
E.5.1 | Primary end point(s) |
Progression Free Survival (PFS)
PFS is defined as the time from the randomization date to the earlier of the dates of (1) the first objective disease progression per RECIST 1.1 with modifications (see protocol for details) or (2) death from any cause. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Interim Analysis - 307 PFS events (28 months post FSE)
Primary Analysis - 613 PFS events (42 months post FSE)
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E.5.2 | Secondary end point(s) |
Overall Survival (OS)
The primary analysis of OS will be conducted when a total of 500 OS events have been observed. The interim analysis of OS is for efficacy only and will be conducted at the same time as the primary analysis of PFS.
it is anticipated that 500 deaths will have occurred 60 to 62 months after the first subject is enrolled. An additional analysis of survival will occur after 700 deaths have been observed. This analysis will be non-inferential and is anticipated to occur approximately 8 years after the first subject is randomized. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Interim Analysis - efficacy only and at same time as PFS Primary Analysis - (613 PFS events, 42 months post FSE)
PA - 500 OS events (60-62 months after FSE)
Additional Analysis - 700 OS events (approximately 8 years after FSE)
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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 | Yes |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | Yes |
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
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 | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
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 | Yes |
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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 100 |
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 | No |
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 |
Canada |
Japan |
European Union |
Hong Kong |
Korea, Republic of |
Russian Federation |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
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: later time of when all subjects have been followed for survival status and disposition (consent withdrawal, lost to follow-up) for 75 months after the last subject has been randomized or when 700 subjects have died. |
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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 | 8 |
E.8.9.1 | In the Member State concerned months | 4 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 8 |
E.8.9.2 | In all countries concerned by the trial months | 4 |
E.8.9.2 | In all countries concerned by the trial days | 0 |