E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Recurrent partially platinum sensitive or resistant epithelial ovarian, primary peritoneal, or fallopian tube cancer |
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E.1.1.1 | Medical condition in easily understood language |
Fallopian Tube Cancer
Ovarian Cancer
Primary Peritoneal Cancer |
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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 | 17.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10066697 |
E.1.2 | Term | Ovarian cancer recurrent |
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 determine if AMG 386 plus pegylated liposomal doxorubicin (PLD) is superior to placebo plus PLD as measured by progression-free survival (PFS). |
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E.2.2 | Secondary objectives of the trial |
To evaluate the effect of AMG 386 plus PLD compared to PLD on overall survival (OS). |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
•Female of age 18 years or older
• Histologically or cytologically documented invasive epithelial ovarian, primary peritoneal, or fallopian tube cancer
- Subjects with pseudomyxoma, mesothelioma, unknown primary tumor, sarcoma, carcinosarcoma, or neuroendocrine histology are excluded
- Subjects with borderline ovarian cancer, ie, subjects with low malignant potential tumors, are excluded
• Radiographically documented disease progression either on or following the last dose of the prior regimen for epithelial ovarian, primary peritoneal, or fallopian tube cancer
• Radiographically evaluable disease per RECIST 1.1 with modifications
- There must be radiographically visible tumor
- Subjects with only ascites, pericardial, or pleural effusion are excluded
• Subjects must have had one prior platinum-based chemotherapeutic regimen for management of primary disease containing carboplatin, cisplatin, or another organoplatinum compound. This initial treatment may have included intraperitoneal therapy, high-dose therapy, consolidation therapy, neoadjuvant chemotherapy with interval surgery, bevacizumab or extended therapy administered after surgical or non-surgical assessment.
- Subjects are allowed to have received, but are not required to have received, 2 additional cytotoxic regimens for management of recurrent or persistent disease
• ECOG performance status 0 or 1
• Adequate hematological, renal and hepatic function
• Left ventricular ejection fraction (LVEF) ≥ institutional lower limit of normal
• Gerenrally well controlled blood pressure , defined as systolic blood pressure < 140 mmHg AND diastolic blood pressure < 90 mmHg
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E.4 | Principal exclusion criteria |
• Subjects who have received more than 3 previous regimens of anti-cancer therapy for epithelial ovarian, primary peritoneal or fallopian tube cancer
• Subjects treated with pegylated liposomal doxorubicin (PLD) or any anthracycline-based or mitoxantrone-based chemotherapy
• Subjects with primary platinum-refractory disease
- Subjects with recurrence or progression during the first 6 cycles or < 6 months after the beginning of the first-line platinum-based chemotherapy are excluded
• Subjects with platinum-free interval (PFI) > 12 months from their last platinum-based therapy
• History of arterial or venous thromboembolism within 12 months prior to randomization
• History of central nervous system metastasis
• Clinically significant cardiac disease within 12 months prior to randomization
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is progression-free survival (PFS). PFS is defined as the time from the date of randomization to the earliest of the dates of first radiologic disease progression per RECIST 1.1 with modifications, or death from any cause. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
When a minimum of 170 PFS events have been observed |
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E.5.2 | Secondary end point(s) |
• Overall survival (OS): time from randomization date to date of death.
Subjects who have not died by the analysis data cutoff date will be
censored at their last contact date prior to the cutoff date. Subjects
known to be alive or dead after the data cutoff date are censored at the
data cutoff date.
• Objective response rate (ORR)
• Duration of response (DOR)
• CA-125 response rate per GCIG criteria
• Change in CA-125
• Change in tumour burden
• Incidence of adverse events and significant laboratory abnormalities
• Pharmacokinetics of AMG 386 (eg, Cmax and Cmin)
• Incidence of anti-AMG 386 antibody formation
• Patient reported HRQOL and ovarian cancer related symptoms using FACT-O
• Overall health status using EQ-5D |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
When a minimum of 170 OS events have been observed |
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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 | 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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 48 |
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 |
Australia |
Canada |
European Union |
Hong Kong |
New Zealand |
Singapore |
Taiwan |
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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The end of study will occur 60 months after the last subject is randomized if all subjects have completed study treatment by that date. |
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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 | 3 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 7 |
E.8.9.2 | In all countries concerned by the trial months | 8 |
E.8.9.2 | In all countries concerned by the trial days | 0 |