E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Metastatic colorectal cancer, KRAS wild-type (WT) or mutant, with disease progression after first line treatment with an oxaliplatin-containing regimen. |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10052358 |
E.1.2 | Term | Colorectal cancer metastatic |
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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 gather preliminary evidence of superior activity, of RO5083945 added to FOLFIRI versus FOLFIRI + cetuximab in terms of progression free survival (PFS) in patients with KRAS WT colorectal cancer • to gather preliminary evidence of superior activity, of RO5083945 added to FOLFIRI versus FOLFIRI alone in terms of progression free survival (PFS) in patients with KRAS mutant colorectal cancer |
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E.2.2 | Secondary objectives of the trial |
to evaluate best overall response rate (ORR) • to evaluate duration of response • to evaluate clinical benefit rate (CBR) • to evaluate overall survival • to evaluate the safety profile of patients treated with RO5083945 in combination with FOLFIRI versus FOLFIRI + cetuximab or FOLFIRI alone • to assess the effect of concomitant FOLFIRI on the pharmacokinetics of RO5083945 and vice versa • to evaluate the relationship between immune effector cells (in blood and tumor) and clinical outcome parameters (e.g. responders vs. non responders, PFS) • to evaluate the relationship between key upstream (e.g. ligands) and downstream EGFR markers (in tumor) and clinical outcome parameters (e.g. responders vs. non responders, PFS) • to compare fresh (new) vs. archival tumor biopsies (e.g. for EGFR expression) |
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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 |
Roche Clinical Repository sub-study (RCR) Specimens for dynamic (non-inherited) (plasma and RNA) biomarker discovery and validation will be collected from all patients participating in the trial. These specimens will be used for research purposes to identify biomarker that are predicitve of response to RO5083945 treatment ( in term of dose, safety and tolerability) and will help to better understand the pathogenesis, course and outcome of mCRC and related diseases. Protocol version: the protocol is part of the main protocol (see section A4) |
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E.3 | Principal inclusion criteria |
- Adult patients, >/= 18 years of age - Carcinoma of the colon and/or rectum - Disease progression during or within 6 months of last dose of oxaliplatin containing first-line combination therapy for metastatic disease - ECOG performance status 0-1 - Adequate hematological, renal and liver function
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E.4 | Principal exclusion criteria |
- Prior treatment with monoclonal antibody/small molecule against epidermal growth factor receptor (EGFR) - Prior treatment with irinotecan - Radiotherapy within the last 4 weeks before first dose of study drug (except for limited field palliative radiotherapy for bone pain relief) - CNS metastasis - History of or active autoimmune disorders/conditions
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary variable is PFS defined as the time between randomization and date of first documented disease progression or death, whichever occurs first. |
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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) | 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.8.3 |
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 | 66 |
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 | 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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A survival update will be performed 12 months after enrollment of the last subject. This additional analysis will be appended to the main report. The study will formally end once the survival update has taken place or the last patient has completed the safety follow-up visit or withdrawn from the study prior to that time (whichever occurs last), but may be prematurely terminated by the sponsor. |
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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 | 1 |
E.8.9.1 | In the Member State concerned months | 7 |
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 | 1 |
E.8.9.2 | In all countries concerned by the trial days | 0 |