Panitumumab and Irinotecan as Third-Line Therapy in Treating Patients With Metastatic Colorectal Cancer
RATIONALE: Monoclonal antibodies, such as panitumumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Drugs used in chemotherapy, such as irinotecan, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving panitumumab together with irinotecan may kill more tumor cells.
PURPOSE: This phase II clinical trial is studying giving panitumumab together with irinotecan to see how well it works as third-line therapy in treating patients with metastatic colorectal cancer.
Drug: irinotecan hydrochloride
Genetic: chromogenic in situ hybridization
Genetic: fluorescence in situ hybridization
Genetic: gene expression analysis
Other: laboratory biomarker analysis
|Study Design:||Masking: Open Label
Primary Purpose: Treatment
|Official Title:||An Open-label Phase II Clinical Trial of Panitumumab in Combination With Irinotecan for Patients With Advanced Metastatic Colorectal Cancer Without KRAS Mutation (Wild Type) in Third Line Chemotherapy (Patients Pretreated With FOLFOX or XELOX ± Bevacizumab and Irinotecan Alone or FOLFIRI or CAPIRI ± Bevacizumab) [PIMABI]|
- Objective response rate (ORR; radiologically confirmed complete response [CR] or partial response [PR]) during the combination therapy phase [ Designated as safety issue: No ]
- ORR during the entire treatment phase (i.e., combination therapy and monotherapy) [ Designated as safety issue: No ]
- Disease control rate (DCR) [ Designated as safety issue: No ]
- Duration of response [ Designated as safety issue: No ]
- Time to response [ Designated as safety issue: No ]
- Progression-free survival time [ Designated as safety issue: No ]
- Time to progression [ Designated as safety issue: No ]
- Duration of stable disease [ Designated as safety issue: No ]
- Time to treatment failure [ Designated as safety issue: No ]
- Correlation between KRAS and KRAF mutations, EGFR gene copy number, and ORR and DCR [ Designated as safety issue: No ]
- Incidence and severity of adverse events [ Designated as safety issue: Yes ]
- Changes in laboratory values [ Designated as safety issue: Yes ]
- Change in vital signs [ Designated as safety issue: Yes ]
- Investigational medicinal product compliance [ Designated as safety issue: Yes ]
- Incidence of dose adjustments [ Designated as safety issue: Yes ]
- Incidence of concurrent medications [ Designated as safety issue: Yes ]
- Changes from baseline over time in WHO performance status [ Designated as safety issue: Yes ]
- Biomarkers (EGFR amplification status by chromogenic in situ hybridization and FISH, KRAS and KRAF mutations, and STAT3 expression [ Designated as safety issue: No ]
|Study Start Date:||June 2008|
|Study Completion Date:||June 2012|
|Primary Completion Date:||June 2012 (Final data collection date for primary outcome measure)|
- To assess the objective response rate when panitumumab is administered in combination with irinotecan hydrochloride as third-line therapy in patients with advanced metastatic colorectal cancer without KRAS mutation (wild type) previously treated with FOLFOX or XELOX chemotherapy with or without bevacizumab and irinotecan hydrochloride alone or FOLFIRI or CAPIRI chemotherapy with or without bevacizumab.
- To assess the efficacy in terms of disease control rate, duration of response, time to response, progression-free survival, time to progression, time to treatment failure, and duration of stable disease.
- To assess the efficacy and safety of this regimen, followed by panitumumab alone in patients who discontinue third-line irinotecan hydrochloride due to toxicity.
- To correlate this regimen with EGFR expression, detection of the functional genetic polymorphisms of the EGFR gene, EGFR gene amplification (FISH), EGFR activation detection, EGFR downstream protein and gene expression parameters, proteomics, and epigenetics.
OUTLINE: This is a multicenter study.
Patients receive panitumumab IV over 30-90 minutes and irinotecan hydrochloride IV over 90 minutes on day 1. Patients who discontinue irinotecan hydrochloride may receive panitumumab monotherapy. Courses repeat every 14 days in the absence of disease progression and unacceptable toxicity.
Archived tumor tissue specimens are obtained at baseline for correlative laboratory studies. Tissue samples are analyzed for EGFR amplification status by chromogenic in situ hybridization and fluorescence in situ hybridization, KRAS and KRAF mutations, and STAT3 expression.
After completion of study therapy, patients are followed at approximately 56 days.
|Centre Paul Papin|
|Angers, France, 49036|
|Hopital Prive Jean Mermoz|
|Lyon, France, 69008|
|Hopital Clinique Claude Bernard|
|Metz, France, 57072|
|Centre Hospitalier Intercommunal Le Raincy - Montfermeil|
|Montfermeil, France, 93370|
|Hopital Saint Antoine|
|Paris, France, 75571|
|Paris, France, 75013|
|Hopital Bichat - Claude Bernard|
|Paris, France, 75018|
|Paris, France, 75970|
|Suresnes, France, 92151|
|Principal Investigator:||Thierry Andre, MD||Groupe Cooperateur Multidisciplinaire en Oncologie (GERCOR)|