Panitumumab and Irinotecan as Third-Line Therapy in Treating Patients With Metastatic Colorectal Cancer
- Conditions
- Colorectal Cancer
- Interventions
- Genetic: Chromogenic in situ hybridizationGenetic: Fluorescence in situ hybridizationGenetic: Gene expression analysisOther: Laboratory biomarker analysis
- Registration Number
- NCT00655499
- Lead Sponsor
- GERCOR - Multidisciplinary Oncology Cooperative Group
- Brief Summary
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.
- Detailed Description
OBJECTIVES:
Primary
* 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.
Secondary
* 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.
Tertiary
* 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 65
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Panitumumab + CPT11 (irinotecan hydrochloride) Gene expression analysis 1 cycle every 14 days (J1= J15) Panitumumab + CPT11 (irinotecan hydrochloride) Laboratory biomarker analysis 1 cycle every 14 days (J1= J15) Panitumumab + CPT11 (irinotecan hydrochloride) Chromogenic in situ hybridization 1 cycle every 14 days (J1= J15) Panitumumab + CPT11 (irinotecan hydrochloride) Fluorescence in situ hybridization 1 cycle every 14 days (J1= J15) Panitumumab + CPT11 (irinotecan hydrochloride) Panitumumab 1 cycle every 14 days (J1= J15) Panitumumab + CPT11 (irinotecan hydrochloride) Irinotecan hydrochloride 1 cycle every 14 days (J1= J15)
- Primary Outcome Measures
Name Time Method Objective Response Rate (ORR) During the Combination Therapy Phase Up to 20 months Per the modified Response Evaluation Criteria in Solid Tumors (m-RECIST) for target lesions and radiogically assessed (CT Scans; optionally MRI): Complete Response (CR; Disappearance of all target lesions) or Partial Response (PR; At least a 30% decrease in the sum of the LD of target lesions) during the combination therapy phase.Overall Response (OR) = CR + PR.
- Secondary Outcome Measures
Name Time Method Disease Control Rate (DCR) Up to 20 months Per the modified Response Evaluation Criteria in Solid Tumors (m-RECIST) for target lesions and radiogically assessed (CT Scans; optionally MRI): confirmed complete (CR; Disappearance of all target lesions) or partial response (PR; At least a 30% decrease in the sum of the longest diameter of target lesions), or stable disease (SD; Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for disease progression, taking as reference the nadir longest diameter since the treatment started) while on the combination therapy treatment phase or over the entire treatment strategy. DCR = CR / PR / SD
Progression-free Survival (PFS) Up to 20 months PFS was defined as time from enrollment date to date of first radiologically observed progression or death (whichever comes first) during the combination therapy phase or over the entire treatment strategy.
Per the Response Evaluation Criteria in Solid Tumors (RECIST) analyzed using Kaplan-Meier methods and the quartiles and event rates at various weeks presented with 95% CIs.Overall Survival (OS) Up to 20 months OS was defined as time from inclusion to death (from any cause or to the last date the patient was known to be alive) during the combination therapy phase or over the entire treatment strategy.
Per the Response Evaluation Criteria in Solid Tumors (RECIST) analyzed using Kaplan-Meier methods and the quartiles and event rates at various weeks presented with 95% CIs.
Trial Locations
- Locations (9)
Hopital Clinique Claude Bernard
🇫🇷Metz, France
Hopital Prive Jean Mermoz
🇫🇷Lyon, France
Centre Hospitalier Intercommunal Le Raincy - Montfermeil
🇫🇷Montfermeil, France
Hopital Bichat - Claude Bernard
🇫🇷Paris, France
Hopital Pitie-Salpetriere
🇫🇷Paris, France
Hopital Foch
🇫🇷Suresnes, France
Hopital Saint Antoine
🇫🇷Paris, France
Hopital Tenon
🇫🇷Paris, France
Centre Paul Papin
🇫🇷Angers, France