E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Metastatic colorectal cancer (mCRC) |
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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 | 10052362 |
E.1.2 | Term | Metastatic colorectal cancer |
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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 assess the differences in progression-free survival at 6 months in subjects with KRAS wild-type metastatic colorectal cancer receiving second line treatment (after failure of a previous irinotecan and 5FU based regimen) with panitumumab plus XELOX compared to the treatment with XELOX alone, without major safety problems |
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E.2.2 | Secondary objectives of the trial |
To assess that, for subjects with KRAS wild-type metastatic colorectal cancer, objective response rate (ORR), disease control rate (DCR), duration of response (DOR), time to progression (TTP), duration of stable disease (DOSD), time to treatment failure and overall survival time (OS) are greater and time to response (TTR) is shorter for subjects receiving second line treatment with panitumumab plus XELOX than for subjects treated with XELOX alone. To assess the differences in overall progression-free and overall survival between subjects with KRAS wild-type and KRAS mutant colorectal cancer who receive XELOX as second-line treatment. |
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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 |
Title: Translational Research Date: 11.12.2009 (component part of the trial) Version: 4.0 (component part of the trial) Objectives: EGFR plays a critical role in tumor progression by stimulating cell cycle progression, invasion, and metastasis. The overexpression seen in many tumors maybe due to gene amplification, mutations or transcriptional abnormalities.
Currently, immunohistochemistry is the standard method for evaluation of EGFR expression. However, there are reports that EGFR expression determined by this method does not correlate with response to blocking agents of the EGFR pathway in lung and colorectal cancers.
The analyses of polymorphisms, the phosphorylation status of EGFR and the expression of the down stream targets may provide the possibility to identify additional predictive markers in patients treated with Panitumumab.
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E.3 | Principal inclusion criteria |
Male or female patients aged 18 years or more, with histologically or cytologically-confirmed and radiologically-measurable metastatic colorectal cancer.
One prior chemotherapy regimen for mCRC consisting of first-line fluoropyrimidine and irinotecan based chemotherapy. Subjects must have disease progression (as assessed by the investigator) and must be no candidates for primary metastectomy.
Measurable disease according to RECIST 1.1 guidelines. All sites of disease must have been evaluated within 28 days prior to registration / randomization, and diagnosed by the investigator.
Liver and kidney function within defined ranges and sufficient bone marrow reserve.
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E.4 | Principal exclusion criteria |
Central nervous system metastases, or significant cardiovascular disease. Prior anti-EGFR antibody therapy (e.g. cetuximab) or treatment with small molecule EGFR tyrosine kinase inhibitors (e.g. erlotinib). Prior treatment with oxaliplatin for metastatic disease. Adjuvant therapy with oxaliplatin based combination for non-metastatic disease is allowed if terminated > 6 months prior to initiation of screening and without progression during the treatment with oxaliplatin. Any condition interfering with study drug therapy as defined in the exclusion criteria. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Progression-free survival (PFS) rate at 6 months The primary efficacy analysis will be based on the progression-free survival rate at 6 months, calculated as a “crude” rate by dividing the number of patients alive free from progression at this time. |
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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 | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
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 | 25 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
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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This clinical trial starts when the first patient is randomized and ends when all patients have finished follow-up. Recruitment phase: 24 months Duration of treatment: approximately 6 months Follow-up phase: 6 months after the last patient stopped treatment (incl. 56 days safety follow-up) |
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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 | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |