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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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 | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10052358 |
E.1.2 | Term | Colorectal 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 | 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 | No |
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.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
- Overall Response Rate: tumour assessments by CT scan or MRI according to RECIST criteria - Duration of response: time from complete or partial response to disease progression or death
- Clinical benefit rate: stable disease for >6 weeks, complete response or partial response; tumour assessments by CT scan or MRI according to RECIST criteria
- Overall survival
- Incidence of adverse events
- Effect of concomitant FOLFIRI on pharmacokinetics of RO5083945 and vice versa |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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.8.5 | 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 | 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 |
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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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Follow-up for survival will continue until all patients have either died or are lost to follow up, or the sponsor decides to end the trial, whichever occurs first.
The study will formally end once the survival follow-up is complete 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 | 2 |
E.8.9.1 | In the Member State concerned months | 1 |
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 |