E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
metastatic adenocarcinoma of the pancreas |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10033606 |
E.1.2 | Term | Pancreatic cancer non-resectable |
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 | 14.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10033605 |
E.1.2 | Term | Pancreatic 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 | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To determine if the treatment of AMG 479 at 12 mg/kg and/or 20 mg/kg in combination with gemcitabine improves overall survival (OS) as compared with placebo in combination with gemcitabine in subjects with metastatic adenocarcinoma of the pancreas. |
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E.2.2 | Secondary objectives of the trial |
• To evaluate progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 • To evaluate the survival rate at 12-months, and at the timepoints of 3, 6, 9, 18, and 24 months • objective response rate, time to disease progression, duration of response, and disease control rate (partial response [PR] + complete response [CR] + stable disease [SD]) as per RECIST version 1.1 • subject incidence of adverse events, significant laboratory abnormalities, and immunogenicity • AMG 479 dose exposure, dose intensity, and pharmacokinetic (PK) parameters and to evaluate relationships between AMG 479 exposure measures and selected safety and efficacy measures • gemcitabine dose exposure, dose intensity in all subjects, and gemcitabine PK parameters in a subset of subjects See protocol for more details |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
If the subject signs the additional optional pharmacogenetic informed consent, DNA will be used for exploratory pharmacogenetic analyses. These analyses differ from the above blood and tumor analyses because they focus on evaluation of the different heritable gene forms in DNA that may influence the different responses subjects have to a study treatment. The goals of exploratory studies include the use of genetic markers to help in the investigation of cancer and to identify persons who may have the best possible response to AMG 479. To study the effects of human heritable genetic variation on investigational product response, we plan to conduct exploratory pharmacogenetic studies as an optional part of this study. No additional blood samples will be collected for this part of the study; however, for those subjects that consent to participate in optional PG studies, DNA will be extracted from the cell pellet left-over after biomarker plasma preparation. |
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E.3 | Principal inclusion criteria |
Subjects must have histologically or cytologically confirmed metastatic adenocarcinoma of the pancreas (American Joint Committee on Cancer Stage IV); ECOG score of 0 or 1; Men or women ≥ 18 years of age. |
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E.4 | Principal exclusion criteria |
Islet cell, acinar cell carcinoma, non-adenocarcinoma, (eg, lymphoma, sarcoma, etc), adenocarcinoma originated from biliary tree or cystadenocarcinoma; currently treated or previously treated with biologic, small molecule, immunotherapy, chemotherapy (eg, gemcitabine), radiotherapy, chemoradiotherapy or other agents for pancreatic cancer. |
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E.5 End points |
E.5.1 | Primary end point(s) |
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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 | 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.8.3 |
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 | 4 |
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 | 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 | 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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Primary Completion: The final analysis will be 24 months after the date the last subject is randomized, however, the final analysis may occur earlier if all subjects who are under active observation (ie, have not withdrawn full consent and have a last contact date within 14 weeks) have died. End of Study: The end of study will be the later of the Primary Completion or when the last subject discontinues all protocol therapy and has had the opportunity to complete the safety follow-up visit. |
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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 | 8 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
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 |