Panitumumab (ABX-EGF) Monotherapy in Patients With Metastatic Colorectal Cancer

Study Overview
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Brief Summary
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The purpose of this study is to determine that panitumumab will have clinically meaningful anti-tumor activity in patients with metastatic colorectal cancer who have developed progressive disease or relapsed while on or after prior fluoropyrimidine, irinotecan and oxaliplatin chemotherapy.

Official Title
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A Phase 2 Multicenter Single Arm Clinical Trial of ABX-EGF Monotherapy in Subjects With Metastatic Colorectal Cancer Whose Tumors Express Low or Negative EGFr Levels of Immunohistochemistry Following Treatment With Fluoropyrimidine, Irinotecan, and Oxaliplatin Chemotherapy

Conditions
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Metastases, Colorectal Cancer

Intervention / Treatment
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* Drug: Panitumumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pathologic diagnosis of colorectal adenocarcinoma (diagnostic tissue obtained by tissue biopsy) Metastatic colorectal carcinoma Eastern Cooperative Oncology Group of 0, 1 or 2 Documented evidence of disease progression during, or following treatment, with fluoropyrimidine, irinotecan and oxaliplatin chemotherapy for metastatic colorectal cancer Radiographic documentation of disease progression during or within 6 months following the most recent chemotherapy regimen is required Bidimensionally measurable disease Tumor expressing low to negative levels of epidermal growth factor receptor (EGFr) by immunohistochemistry At least 2 but no more than 3 prior chemotherapy regimens for metastatic colorectal cancer Adequate hematologic, renal and hepatic function Exclusion Criteria: Symptomatic brain metastases requiring treatment Patient with a history of interstitial pneumonitis or pulmonary fibrosis or evidence of interstitial pneumonitis or pulmonary fibrosis Use of systemic chemotherapy or radiotherapy within 30 days before enrollment Prior anti-EGFr antibody therapy with the exception of the small molecule EGFr tyrosine kinase inhibitors, which are permitted Prior anti-tumor therapies including prior experimental agents or approved anti-tumor small molecules and biologics of short (less than 1 week) serum half-life within 30 days before enrollment, or prior experimental or approved proteins within 6 weeks before enrollment

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Panitumumab<br>Panitumumab was administered by intravenous (IV) infusion at a dose of 6 mg/kg once every 2 weeks until participants developed progressive disease, were unable to tolerate investigational product, or discontinued for other reasons. | Drug: Panitumumab<br>* Administered by intravenous infusion<br>* Other names: Vectibix®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Tumor Response Through Week 16 | Confirmed objective tumor response was defined as a complete response or partial response from enrollment through Week 16. Tumor response was monitored, beginning at Week 8, per a modified version of the World Health Organization (WHO) criteria for tumor response and progression by an independent review committee central assessment. Complete response was defined per modified WHO criteria as disappearance of all lesions (index and non-index). Partial response was defined as ≥ 50% decrease from Baseline in the sum of the products of the longest diameters (SPD) of index lesions. Scans were required to confirm a complete or partial response no earlier than 4 weeks from the time a response of complete or partial response was first documented. | From enrollment through Week 16 | 
| Duration of Response | Kaplan-Meier estimate of time time from first objective response to first observed progression of disease or death if the death was due to disease progression (whichever comes first) among participants who had a response at any time on study. Participants who responded and did not progress while on study or who died for reasons other than disease progression while on study were censored at their last evaluable assessment date. | From enrollment until the data cut-off date of 22 December 2006. The median follow-up time was 36 weeks. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Tumor Response Throughout the Study | Confirmed objective tumor response was defined as a complete response or partial response from enrollment through to the data cut-ff date. Tumor response was monitored, beginning at Week 8, per a modified version of the World Health Organization (WHO) criteria for tumor response and progression by an independent review committee central assessment. Complete response was defined per modified WHO criteria as disappearance of all lesions (index and non-index). Partial response was defined as ≥ 50% decrease from Baseline in the sum of the products of the longest diameters (SPD) of index lesions. Scans were required to confirm a complete or partial response no earlier than 4 weeks from the time a response of complete or partial response was first documented. | From enrollment until the data cut-off date of 22 December 2006. The median follow-up time was 36 weeks. | 
| Time to Initial Objective Response | Time from date of enrollment to first objective response; participants with stable disease at their last evaluable assessment date were censored at this date and participants with progressive disease while on study were censored after the last response was observed for all participants. | From enrollment until the data cut-off date of 22 December 2006. The median follow-up time was 36 weeks. | 
| Progression-free Survival Time | Kaplan-Meier estimate of median time from date of enrollment to date of first observed progression or death (whichever comes first); participants who did not progress while on study and did not die while on study were censored at their last evaluable assessment date. | From enrollment until the data cut-off date of 22 December 2006. The median follow-up time was 36 weeks. | 
| Time to Disease Progression | Kaplan-Meier estimate of median time from date of enrollment to date of first observed progression or death date if the death was due to disease progression (whichever comes first); participants who have not progressed while on study or died for reasons other than disease progression while on study were censored at their last evaluable assessment date. | From enrollment until the data cut-off date of 22 December 2006. The median follow-up time was 36 weeks. | 
| Time to Treatment Failure | Kaplan-Meier estimate of median time from date of enrollment to date decision was made to end the treatment phase for any reason; participants who complete the treatment phase or who remain in the treatment phase at the completion of the study were censored at this time. | From enrollment until the data cut-off date of 22 December 2006. The median follow-up time was 36 weeks. | 
| Duration of Stable Disease | Kaplan-Meier estimate of median time from date of enrollment to date of first observed progression or death date if the death was due to disease progression (whichever comes first); in those participants who had a best response of stable disease. Stable Disease is defined as neither sufficient shrinkage of index lesions to qualify for a partial response nor sufficient increase to qualify for progressive disease taking as reference the nadir sum of the products of the longest diameters since the treatment started. | From enrollment until the data cut-off date of 22 December 2006. The median follow-up time was 36 weeks. | 
| Overall Survival | Kaplan-Meier estimate of time to death from any cause; participants who had not died while on study or were lost to follow-up were censored at their last contact date. | From enrollment until the data cut-off date of 22 December 2006. The median follow-up time was 36 weeks. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Colon, Rectal Cancer, ABX-EGF, Panitumumab, EGFr, Immunex, Abgenix, Amgen, Metastatic Colorectal Cancer, Vectibix