Back to resultsPanitumumab Plus FOLFIRI in First-line Treatment of Metastatic Colorectal Cancer
Primary Purpose
Metastatic Colorectal Cancer
Status
Completed
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Panitumumab
FOLFIRI
Sponsored by
About this trial
This is an interventional treatment trial for Metastatic Colorectal Cancer
Eligibility Criteria
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.
Sites / Locations
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Panitumumab plus FOLFIRI
Arm Description
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.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
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.
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.
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.
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.
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.
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.
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.
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.
Resection Rate
The percentage of participants who underwent a surgical procedure that resulted in partial reduction or complete eradication of all metastatic disease.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00508404
Brief Title
Panitumumab Plus FOLFIRI in First-line Treatment of Metastatic Colorectal Cancer
Official Title
A Single Arm Multicentre Phase II Study of Panitumumab in Combination With Irinotecan/5-fluorouracil/Leucovorin in Patients With Metastatic Colorectal Cancer
Study Type
Interventional
2. Study Status
Record Verification Date
November 2019
Overall Recruitment Status
Completed
Study Start Date
May 9, 2007 (Actual)
Primary Completion Date
June 1, 2009 (Actual)
Study Completion Date
June 12, 2012 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Amgen
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
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).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Metastatic Colorectal Cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
154 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Panitumumab plus FOLFIRI
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Panitumumab
Other Intervention Name(s)
Vectibix
Intervention Description
Administered by intravenous infusion
Intervention Type
Drug
Intervention Name(s)
FOLFIRI
Intervention Description
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.
Primary Outcome Measure Information:
Title
Objective Response Rate
Description
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.
Time Frame
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 Measure Information:
Title
Objective Response by 17 Weeks
Description
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.
Time Frame
Up to Week 17
Title
Disease Control Rate
Description
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.
Time Frame
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
Title
Duration of Response
Description
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.
Time Frame
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.
Title
Time to Initial Objective Response
Description
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.
Time Frame
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.
Title
Progression-free Survival
Description
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.
Time Frame
From enrollment until the data cut-off date of 18 June 2009; median follow-up time was 34 weeks.
Title
Time to Disease Progression
Description
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.
Time Frame
From enrollment until the data cut-off date of 18 June 2009; median follow-up time was 34 weeks.
Title
Duration of Stable Disease
Description
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.
Time Frame
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.
Title
Time to Treatment Failure
Description
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.
Time Frame
From enrollment until the data cut-off date of 18 June 2009; median follow-up time was 34 weeks.
Title
Time to Disease Relapse Following Surgical Intervention
Description
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.
Time Frame
From enrollment until the data cut-off date of 18 June 2009; median follow-up time was 34 weeks.
Title
Resection Rate
Description
The percentage of participants who underwent a surgical procedure that resulted in partial reduction or complete eradication of all metastatic disease.
Time Frame
From enrollment until the data cut-off date of 18 June 2009; median follow-up time was 34 weeks.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
MD
Organizational Affiliation
Amgen
Official's Role
Study Director
12. IPD Sharing Statement
Citations:
PubMed Identifier
21960318
Citation
Kohne CH, Hofheinz R, Mineur L, Letocha H, Greil R, Thaler J, Fernebro E, Gamelin E, Decosta L, Karthaus M. First-line panitumumab plus irinotecan/5-fluorouracil/leucovorin treatment in patients with metastatic colorectal cancer. J Cancer Res Clin Oncol. 2012 Jan;138(1):65-72. doi: 10.1007/s00432-011-1061-6. Epub 2011 Sep 30.
Results Reference
background
PubMed Identifier
23020584
Citation
Thaler J, Karthaus M, Mineur L, Greil R, Letocha H, Hofheinz R, Fernebro E, Gamelin E, Banos A, Kohne CH. Skin toxicity and quality of life in patients with metastatic colorectal cancer during first-line panitumumab plus FOLFIRI treatment in a single-arm phase II study. BMC Cancer. 2012 Sep 29;12:438. doi: 10.1186/1471-2407-12-438.
Results Reference
background
PubMed Identifier
31515083
Citation
Taieb J, Geissler M, Rivera F, Karthaus M, Wilson R, Loupakis F, Price T, Tracy M, Burdon P, Peeters M. Relationship Between Tumor Response and Tumor-Related Symptoms in RAS Wild-Type Metastatic Colorectal Cancer: Retrospective Analyses From 3 Panitumumab Trials. Clin Colorectal Cancer. 2019 Dec;18(4):245-256.e5. doi: 10.1016/j.clcc.2019.07.009. Epub 2019 Jul 29.
Results Reference
derived
PubMed Identifier
31300973
Citation
Kohne CH, Karthaus M, Mineur L, Thaler J, Van den Eynde M, Gallego J, Koukakis R, Berkhout M, Hofheinz RD. Impact of Primary Tumour Location and Early Tumour Shrinkage on Outcomes in Patients with RAS Wild-Type Metastatic Colorectal Cancer Following First-Line FOLFIRI Plus Panitumumab. Drugs R D. 2019 Sep;19(3):267-275. doi: 10.1007/s40268-019-0278-8.
Results Reference
derived
Links:
URL
http://www.amgentrials.com
Description
AmgenTrials clinical trials website
Learn more about this trial
Panitumumab Plus FOLFIRI in First-line Treatment of Metastatic Colorectal Cancer
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