E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Metastatic gastric or gastroesophageal adenocarcinoma |
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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 | 10053548 |
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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 |
The primary objective is to demonstrate efficacy in terms of prolonged overall survival time (OS) in patients treated with paclitaxel plus ramucirumab (IMC-1121B) drug product (thereafter referred to as ramucirumab DP) compared to patients treated with paclitaxel plus placebo as second-line treatment of metastatic gastric or gastroesophageal adenocarcinoma after failure of any platin and fluoropyrimidine doublet with or without anthracycline (epirubicin or doxorubicin). |
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E.2.2 | Secondary objectives of the trial |
To evaluate progression-free survival time (PFS) in each arm To evaluate the time to progression (TTP) in each arm To evaluate the best overall response (BOR) and objective response rate (ORR) in each arm To evaluate the safety profile of ramucirumab DP in combination with paclitaxel To evaluate patient-reported outcome (PRO) measures (EORTC QLQ-C30 and EQ-5D) To examine the pharmacodynamic profile of ramucirumab DP, with exploratory analysis of pharmacodynamic biomarkers that may predict efficacy of ramucirumab DP, including but not limited to levels of circulating vascular endothelial growth factor A (VEGF-A), VEGF-B, VEGF-C, VEGF-D, placental growth factor (P1GF), soluble vascular endothelial growth factor receptor-1 (VEGFR-1), and soluble VEGFR 2 To assess the immunogenicity of ramucirumab DP To assess pharmacokinetic parameters of ramucirumab DP |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
The patient has provided signed informed consent and is amenable to compliance with protocol schedules and testing. 2. The patient is at least 18 years of age. 3. The patient has an Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1 at study entry. 4. The patient has a histopathologically or cytologically confirmed diagnosis of gastric or gastroesophageal adenocarcinoma. 5. The patient has metastatic disease or locally advanced, unresectable disease. 6. The patient has experienced documented objective radiographic, clinical, or pathologic (ie, by histology and/or cytology) disease progression during first-line therapy, or within 4 months after the last dose of first-line therapy with any platinum/fluoropyrimidine doublet with or without anthracycline (epirubicin or doxorubicin) for unresectable or metastatic disease.Per l`elenco completo dei criteri di inclusione si prega di fare riferimento al Protocollo versione 1.1 del 08 Luglio 2010. |
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E.4 | Principal exclusion criteria |
1. The patient has squamous cell or undifferentiated gastric cancer. 2. The patient has undergone major surgery within 28 days prior to randomization, or subcutaneous venous access device placement within 7 days prior to randomization. 3. The patient has received any chemotherapy other than platinum and fluoropyrimidine with or without anthracycline for gastric adenocarcinoma. 4. The patient has received previous systemic chemotherapy with a cumulative dose of > 900 mg/m2 of epirubicin or > 400 mg/m2 of doxorubicin. 5. The patient has received any previous systemic therapy (including investigational agents) targeting VEGF or the VEGFR signaling pathways. Other previous targeted therapies are permitted, if stopped at least 28 days prior to randomization. Per l`elenco completo dei criteri di esclusione si prega di fare riferimento al Protocollo versione 1.1 del 08 Luglio 2010. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary EFFICACY endpoint, the OVERALL SURVIVAL time, is defined as the time from the date of randomization to the date of death from any cause. Safety will be evaluated based on reported adverse events, clinical laboratory assessments, vital signs and physical examinations. |
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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 | 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) | 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 | 9 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 79 |
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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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 | 8 |
E.8.9.1 | In the Member State concerned days | 0 |
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 | 8 |
E.8.9.2 | In all countries concerned by the trial days | 0 |