Symptoms and General Pathology

All Conditions

Neoplasms

Digestive System Diseases

Recurrence

Adenocarcinoma

Colorectal Neoplasms

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Colonic Diseases

Intestinal Diseases

Rectal Diseases

Antineoplastic Agents

All Drugs and Chemicals

Herbal and Botanical

Bevacizumab

Irinotecan

Panitumumab

Topoisomerase I Inhibitors

Enzyme Inhibitors

Antineoplastic Agents, Immunological

Cola

Irinotecan hydrochloride

Chromogenic in situ hybridization

Fluorescence in situ hybridization

Gene expression analysis

Laboratory biomarker analysis

Thierry Andre, MD

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.

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.

Panitumumab and Irinotecan as Third-Line Therapy in Treating Patients With Metastatic Colorectal Cancer

An Open-label Phase II Trial of Panitumumab Plus Irinotecan for Patients With Advanced Metastatic Colorectal Cancer Without KRAS Mutation (Wild-type) in Third-line Chemotherapy (FOLFOX/XELOX ± Bevacizumab and Irinotecan Alone or FOLFIRI/CAPIRI ± Bevacizumab)

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.

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

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.

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.

GERCOR - Multidisciplinary Oncology Cooperative Group

Adverse events (AE) were collected during the treatment period and safety follow-up phases and were graded using NCI-CTCAE version 3.0.

1 cycle every 14 days (J1= J15)

panitumumab: Panitumumab : 6mg/kg

irinotecan hydrochloride: 180mg/kg

chromogenic in situ hybridization

fluorescence in situ hybridization

gene expression analysis

laboratory biomarker analysis

Panitumumab + CPT11

1cycle every 14 days (J1=J15). Panitumumab : 6mg/kg in IV infusion over 60 minutes on day 1. Irinotecan : 180mg/m² in IV infusion over 90 minutes on day 1 just after panitumumab administration

Panitumumab Combined With Irinotecan

Age, Categorical

Age, Continuous

Sex: Female, Male

France

Region of Enrollment

ECOG performance status - PS = 0

ECOG - PS=1

ECOG - PS=2

The ECOG Performance Status is a method to assess the functional status of a patient.

* ECOG - PS 0 : Fully active, able to carry on all pre-disease performance without restriction
* ECOG - PS 1 : Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work
* ECOG - PS 2 :Ambulatory and capable of all selfcare but unable to carry out any work activities; up and about more than 50% of waking hours

ECOG Performance status

Colon

Rectum

Both

Primary tumor type

1 metastatic site

>1 metastatic site

Number of metastatic sites

Adjuvant chemotherapy

< 12 months

≥12-24 months

> 24 months

Time between diagnosis and inclusion

Oxaliplatin-based therapy

Irinotecan-based therapy

Oxaliplatin- and irinotecan-based therapy

First line chemotherapy

No second line

Second line chemotherapy

Prior treatment with bevacizumab

69 patients were enrolled in the study. 4 patients were not eligible.Baseline measures are provided for 65 patients

Regulatory affairs

Whole study population

Confirmed wild-type KRAS population

All wild-type population

Patients with KRAS, NRAS or BRAF mutations

69 patients were enrolled in the study. 4 patients were not eligible. 65 eligible patients were analysed

Objective Response Rate (ORR) During the Combination Therapy Phase

Overall period

All Wild-type population

Patients with KRAS, NRAS or BRAF mutation

Disease Control Rate (DCR)

Overall Period

Patient with KRAS, NRAS or BRAF mutations

Progression-free Survival (PFS)

Study population

Overall Survival (OS)

65 patients were eligible (69 patients were enrolled and 4 patients were not eligible).

Overall Study

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Panitumumab and Irinotecan as Third-Line Therapy in Treating Patients With Metastatic Colorectal Cancer	NCT00655499	Colorectal Canc...	Panitumumab Irinotecan hydr... Chromogenic in ... Fluorescence in... Gene expression... Laboratory biom...	18 Years - 80 Years	GERCOR - Multidisciplinary Oncology Cooperative Group
Panitumumab and Irinotecan as Third-Line Therapy in Treating Patients With Metastatic Colorectal Cancer	NCT00655499	Colorectal Canc...	Panitumumab Irinotecan hydr... Chromogenic in ... Fluorescence in... Gene expression... Laboratory biom...	18 Years - 80 Years	GERCOR - Multidisciplinary Oncology Cooperative Group

Spots Global Cancer Trial Database for chromogenic in situ hybridization