Last updated on November 2018

Second-line FOLFIRI + Panitumumab in Subjects With Wild Type RAS Metastatic Colorectal


Brief description of study

To estimate progression-free-survival at 6 months in subjects treated in first-line with panitumumab and FOLFOX and with wild type RAS mCRC confirmed in liquid biopsies before starting second line treatment will be screened for this trial and who have interrupted panitumumab for <3 months (panitumumab continuation). Control arm of subjects treated with FOLFIRI alone will be included.

The combinations of 5-fluorouracil (5-FU) with oxaliplatin (FOLFOX)are considered the backbone chemotherapy for mCRC. Clinical trials have shown the benefit of adding monoclonal antibodies to subjects without mutations in RAS, directed against the epidermal growth factor receptor (EGFR) (cetuximab and panitumumab) to conventional chemotherapy as first-line treatment of mCRC. This trial purposes to study the treatment beyond progression with panitumumab in subjects treated in first-line with an anti-EGFR monoclonal antibody, or rather,the re-introduction of the same targeted therapy after progression to first line.

The clinical hypothesis of this study is that the second-line regimen FOLFIRI + panitumumab, is sufficiently active (defined as a 6-months PFS higher than 30% [based on prior results with second-line FOLFIRI alone] and of at least 50%), justifying further study in this population.

Detailed Study Description

A phase II, multicentre, open-label, randomized two-arm study. Subjects treated in first-line with panitumumab and FOLFOX and with wild type RAS mCRC confirmed in liquid biopsies before starting second line treatment will be screened for this trial. Only subjects who have interrupted panitumumab for < 3 months (panitumumab continuation) will be included.

Eligible subjects will receive FOLFIRI + panitumumab until disease progression, onset of unacceptable drug toxicities, or subject/physician's request to discontinue. A control arm of subjects treated with FOLFIRI alone will be included. Subjects will be assigned in a 3:2 ratio to receive FOLFIRI + panitumumab (Group A) or FOLFIRI alone (Group B). Randomization will be stratified by primary tumour location (left vs right). A blood sample will be obtained at baseline and at disease progression in order to determine the mutational status of RAS/BRAF and other biomarkers.

Tumour response assessment will be performed by the investigator according to Response Evaluation Criteria in Solid Tumours (RECIST) criteria (version 1.1). Subjects will be evaluated for tumour response every 8 weeks until documentation of disease progression. Responding disease will be confirmed no less than 28 days after the criteria for response are first met. Subjects with symptoms suggestive of progressive disease should be evaluated for tumour progression at the time the symptoms occur. After second-line treatment discontinuation, information on subsequent lines of treatments at the physician discretion and survival will be collected in follow-up visits carried out every 12 weeks ( 4 weeks) until the end of the study (approximately 20 months after the inclusion of the last subject in the study).

Clinical Study Identifier: NCT03751176

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