Panitumumab Plus FOLFIRI in First-line Treatment of Metastatic Colorectal Cancer

Study Overview
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Brief Summary
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To estimate the effect of KRAS mutation status (Wild-type versus Mutant) on objective response rate and other measures of efficacy for patients treated with panitumumab in combination with a chemotherapy regimen of irinotecan, 5-fluorouracil, and leucovorin (FOLFIRI) as first-line therapy for metastatic colorectal cancer (mCRC).

Official Title
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A Single Arm Multicentre Phase II Study of Panitumumab in Combination With Irinotecan/5-fluorouracil/Leucovorin in Patients With Metastatic Colorectal Cancer

Conditions
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Metastatic Colorectal Cancer

Intervention / Treatment
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* Drug: Panitumumab
* Drug: FOLFIRI


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosed with histologically- or cytologically-confirmed metastatic adenocarcinoma of the colon and/or rectum. Measurable disease according to modified RECIST guidelines. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2. Paraffin-embedded tissue or unstained tumour slides from primary or metastatic tumour available for central lab analysis. Adequate haematologic, renal, hepatic and metabolic function. Exclusion Criteria: Central nervous system metastases. Prior systemic therapy for the treatment of metastatic colorectal carcinoma with the exception of adjuvant fluoropyrimidine-based chemotherapy given at least six months prior to initiating study treatment. Prior anti-epidermal growth factor receptor (EGFr) antibody therapy (e.g. cetuximab) or treatment with small molecule EGFr tyrosine kinase inhibitors (e.g. erlotinib). Prior radiotherapy within 14 days prior to screening, and for which all signs of early radiological toxicity have not abated. Significant cardiovascular disease including unstable angina or myocardial infarction within six months before initiating study treatment or a history of ventricular arrhythmia. History of interstitial pneumonitis or pulmonary fibrosis or evidence of interstitial pneumonitis or pulmonary fibrosis on baseline chest computed tomography (CT scan. Active inflammatory bowel disease or other bowel disease causing chronic diarrhoea (defined as > 4 loose stools per day). History of Gilbert's syndrome or dihydropyrimidine deficiency. Known positive test for human immunodeficiency virus infection, hepatitis C virus, chronic active hepatitis B infection. Any investigational agent within 30 days before initiation of study treatment. Must not have had a major surgical procedure within 28 days prior to initiation of study treatment. Subject who is pregnant or breast-feeding. Woman or man of childbearing potential not consenting to use adequate contraceptive precautions during the course of the study and for six months after the last study drug administration for women, and one month for men. Other protocol specified criteria and specific details may apply.

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 plus FOLFIRI<br>Participants received 6 mg/kg panitumumab intravenously (IV) once every 14 days in combination with FOLFIRI chemotherapy regimen consisting of irinotecan, infusional 5-fluorouracil, and leucovorin, until diagnosed with radiographic disease progression. | Drug: Panitumumab<br>* Administered by intravenous infusion<br>* Other names: Vectibix;Drug: FOLFIRI<br>* FOLFIRI chemotherapy was initiated on Day 1 of each treatment cycle at the following starting doses: irinotecan 180 mg/m², leucovorin 400 mg/m², 5-fluorouracil bolus 400 mg/m², 5-fluorouracil infusion 2400 mg/m².<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate | Objective response rate is defined as the percentage of participants with a best response of complete response or partial response. Disease assessments are based on investigator review of scans using modified Response Evaluation Criteria in Solid Tumors (RECIST) V1.0 criteria. A complete or partial response was confirmed no less than 4-weeks after the criteria for response were first met. Participants with no post-baseline assessment were considered non-responders. Complete Response (CR): disappearance of all target and non-target lesions and no new lesions. Partial Response (PR): At least a 30% decrease in the size of target lesions with no progression of non-target lesions and no new lesions, or, the disappearance of all target lesions but persistence of 1 or more non-target lesions not qualifying for either CR or progressive disease (PD) and no new lesions. | Tumor response was assessed at Week 8 and every 8 weeks to Week 48 and 3 monthly thereafter until disease progression; median follow-up time was 34 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response by 17 Weeks | The percentage of participants with a best response of complete response or partial response by Week 17. Disease assessments are based on investigator review of scans using modified RECIST V1.0 criteria. A complete or partial response was confirmed no less than 4-weeks after the criteria for response were first met. Participants with no post-baseline assessment were considered non-responders. | Up to Week 17 | 
| Disease Control Rate | The percentage of participants whose best response was either a complete or partial response or stable disease, based on modified RECIST v1.0 criteria as assessed by the Investigator. Stable diease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD of target lesions and no progression of existing non-target lesions and no new lesions, or, the persistence of 1 or more non-target lesions not qualifying for either CR or PD if no target lesions were identified at Baseline. | Tumor response was assessed at Week 8 and every 8 weeks to Week 48 and 3 monthly thereafter until disease progression; median follow-up time was 34 weeks | 
| Duration of Response | Duration of response was calculated only for those participants who had a confirmed complete or partial response, and is defined as the time from first confirmed response to first observed progression. For participants who responded and did not progress by the analysis data cut-off date, duration of response was censored at their last evaluable disease assessment date. Duration of response was analyzed using the Kaplan-Meier method. | Tumor response was assessed at Week 8 and every 8 weeks to Week 48 and 3 monthly thereafter until disease progression; median follow-up time was 34 weeks. | 
| Time to Initial Objective Response | Time to response is the time from the date of enrollment to the date of first confirmed complete or partial response. Participants with a best response of stable disease at the analysis data cut-off date were censored at their last assessment of SD and participants with all other categories of best response were censored at the maximum observed time to a first confirmed response among all responders. Time to initial objective response was analyzed using Kaplan-Meier methods. | Tumor response was assessed at Week 8 and every 8 weeks to Week 48 and 3 monthly thereafter until disease progression; median follow-up time was 34 weeks. | 
| Progression-free Survival | Progression-free survival is the time from the date of enrollment to the date of first observed progression or death, whichever comes first. Participants who were alive and did not progress by the analysis data cut-off date were censored at the last evaluable disease assessment date. Progression-free survival was analyzed using Kaplan-Meier methods. | From enrollment until the data cut-off date of 18 June 2009; median follow-up time was 34 weeks. | 
| Time to Disease Progression | Time to progression is the time from the enrollment date to the date of first observed progression. For participants who had not progressed by the analysis data cutoff date, time to progressive disease was censored at their last evaluable disease assessment date. Time to disease progression was analyzed using Kaplan-Meier methods. | From enrollment until the data cut-off date of 18 June 2009; median follow-up time was 34 weeks. | 
| Duration of Stable Disease | Duration of stable disease was calculated only for participants with a best response of stable disease and is defined as the time from enrollment to first observed PD. For participants who did not progress by the analysis data cut-off date, duration of SD was censored at their last evaluable disease assessment date. Duration of stable disease was estimated using Kaplan-Meier methods. | Tumor response was assessed at Week 8 and every 8 weeks to Week 48 and 3 monthly thereafter until disease progression; median follow-up time was 34 weeks. | 
| Time to Treatment Failure | Time to treatment failure is defined as the time from enrollment to the date the decision was made to end the treatment phase for any reason. For participants who remained in the treatment phase at the analysis data cut-off date, time to treatment failure was censored at the date of their last on-study assessment. Time to treatment failure was analyzed using Kaplan-Meier methods. | From enrollment until the data cut-off date of 18 June 2009; median follow-up time was 34 weeks. | 
| Time to Disease Relapse Following Surgical Intervention | Calculated only for those participants who underwent surgical intervention, and defined as the time from the date of first post-intervention radiographic disease assessment to the date of first observed PD. Participants with no post-intervention disease assessment had their time to relapse set to zero and censored in the analysis. Participants that had evidence of progression / recurrence at their first post-intervention disease assessment had a time to relapse of zero. For participants who had not progressed by the analysis data cut-off date, time to relapse was censored at the date of their last evaluable disease assessment. Time to relapse was analyzed using Kaplan-Meier metjhods. | From enrollment until the data cut-off date of 18 June 2009; median follow-up time was 34 weeks. | 
| Resection Rate | The percentage of participants who underwent a surgical procedure that resulted in partial reduction or complete eradication of all metastatic disease. | From enrollment until the data cut-off date of 18 June 2009; median follow-up time was 34 weeks. |