Back to resultsPRIME: Panitumumab Randomized Trial In Combination With Chemotherapy for Metastatic Colorectal Cancer to Determine Efficacy
Primary Purpose
Metastatic Colorectal Cancer
Status
Completed
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
Panitumumab
FOLFOX regimen
Sponsored by
About this trial
This is an interventional treatment trial for Metastatic Colorectal Cancer focused on measuring Oncology, Cancer, metastatic colorectal cancer, EGFr, Panitumumab, Clinical Trail, Amgen
Eligibility Criteria
Inclusion Criteria: Man or woman at least 18 years old Diagnosis of metastatic colorectal cancer At least 1 uni-dimensionally measurable lesion of at least 20 mm per modified RECIST Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 Paraffin-embedded tumor tissue from the primary tumor or metastasis available for central analyse Exclusion Criteria: History or known presence of central nervous system (CNS) metastases History of another primary cancer, except: Curatively treated in situ cervical cancer, or Curatively resected non-melanoma skin cancer, or Other primary solid tumor curatively treated with no known active disease present and no treatment administered for ≥ 5 years before randomization Prior chemotherapy or systemic therapy for the treatment of metastatic colorectal carcinoma except: adjuvant fluoropyrimidine-based chemotherapy or prior fluoropyrimidine therapy administered solely for the purpose of radiosensitization Prior oxaliplatin therapy Prior anti-epidermal growth factor receptor (EGFr) antibody therapy (eg, cetuximab) or treatment with small molecule EGFr inhibitors (eg, erlotinib) Clinically significant cardiovascular disease (including myocardial infarction, unstable angina, symptomatic congestive heart failure, serious uncontrolled cardiac arrhythmia) 1 year prior to randomization History of interstitial lung disease (eg, pneumonitis or pulmonary fibrosis) or evidence of interstitial lung disease on baseline chest computed tomography (CT) scan Active inflammatory bowel disease or other bowel disease causing chronic diarrhea (defined as > Common terminology criteria (CTC) grade 2 [CTCAE version 3.0]) Peripheral sensory neuropathy with functional impairment
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
FOLFOX + Panitumumab
FOLFOX
Arm Description
Participants received panitumumab, 6 mg/kg on Day 1 and FOLFOX chemotherapy regimen on Days 1 and 2 of each 14-day cycle until disease progression or unacceptable toxicity.
Participants received FOLFOX chemotherapy regimen on Days 1 and 2 of each 14-day cycle until disease progression or until unacceptable toxicity.
Outcomes
Primary Outcome Measures
Progression-free Survival
Progression-free survival (PFS), assessed by central radiological assessment, was defined as the time from randomization to disease progression per modified response evaluation criteria in solid tumors (RECIST) criteria or death. Participants who were alive but did not meet criteria for progression by the data cutoff date were censored at their last evaluable disease assessment date. Progressive disease is defined as a ≥ 20% increase in the size of target lesions or unequivocal progression of existing non-target lesions or any new lesions.
Secondary Outcome Measures
Overall Survival
The definition of overall survival is the time from randomization to death; participants who were alive at the analysis data cutoff were censored at their last contact date.
Percentage of Participants With an Objective Response
Participants were evaluated for tumor response per the modified Response Evaluation Criteria in Solid Tumors (RECIST) criteria every 8 weeks until disease progression. Objective response by central radiological assessment was defined as the incidence of either a confirmed complete or partial response (CR or PR) while on the first-line treatment, as determined by blinded independent central review and confirmed no less than 4-weeks after the criteria for response are first met. CR: Disappearance of all target and non-target lesions and no new lesions. PR: At least a 30% decrease in the sum of the longest diameter of target lesions and no progression of non-target or no new lesions, or, disappearance of all target lesions and the persistence of ≥ 1 non-target lesion not qualifying for either CR or progressive disease. Participants without a post-baseline assessment were considered non-responders.
Time to Progression
Time to progression was defined as time from randomization date to date of disease progression per the modified RECIST criteria.
Duration of Response
Duration of response was calculated only for those participants with a confirmed CR or PR, as the time from the first CR or PR (subsequently confirmed within no less than 4 weeks) to first observed disease progression per modified RECIST criteria, based on a blinded central review.
Number of Participants With Adverse Events (AEs)
A serious adverse event (SAE) is defined as an AE that • is fatal • is life threatening • requires in-patient hospitalization or prolongation of existing hospitalization • results in persistent or significant disability/incapacity • is a congenital anomaly/birth defect • other significant medical hazard. The relationship of the adverse event to the study treatment was assessed by the Investigator by means of the question: "Is there a reasonable possibility that the event may have been caused by the study treatment?"
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00364013
Brief Title
PRIME: Panitumumab Randomized Trial In Combination With Chemotherapy for Metastatic Colorectal Cancer to Determine Efficacy
Official Title
A Randomized, Multicenter, Phase 3 Study to Compare the Efficacy of Panitumumab in Combination With Oxaliplatin/ 5-fluorouracil/ Leucovorin to the Efficacy of Oxaliplatin/ 5-fluorouracil/ Leucovorin Alone in Patients With Previously Untreated Metastatic Colorectal Cancer
Study Type
Interventional
2. Study Status
Record Verification Date
November 2022
Overall Recruitment Status
Completed
Study Start Date
August 1, 2006 (Actual)
Primary Completion Date
August 1, 2009 (Actual)
Study Completion Date
March 22, 2013 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Amgen
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The purpose of this study is to determine the treatment effect of panitumumab in combination with FOLFOX compared to FOLFOX alone as first line therapy for metastatic colorectal cancer
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Metastatic Colorectal Cancer
Keywords
Oncology, Cancer, metastatic colorectal cancer, EGFr, Panitumumab, Clinical Trail, Amgen
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
1183 (Actual)
8. Arms, Groups, and Interventions
Arm Title
FOLFOX + Panitumumab
Arm Type
Experimental
Arm Description
Participants received panitumumab, 6 mg/kg on Day 1 and FOLFOX chemotherapy regimen on Days 1 and 2 of each 14-day cycle until disease progression or unacceptable toxicity.
Arm Title
FOLFOX
Arm Type
Active Comparator
Arm Description
Participants received FOLFOX chemotherapy regimen on Days 1 and 2 of each 14-day cycle until disease progression or until unacceptable toxicity.
Intervention Type
Drug
Intervention Name(s)
Panitumumab
Other Intervention Name(s)
Vectibix®
Intervention Description
Panitumumab 6 mg/kg over on Day 1 of each 14-day cycle, just prior to the administration of chemotherapy.
Intervention Type
Drug
Intervention Name(s)
FOLFOX regimen
Intervention Description
The FOLFOX regimen consisted of oxaliplatin 85 mg/m^2 intravenous (IV) infusion on Day 1, leucovorin, 200 mg/m^2 (racemate) on Days 1 and 2 and 5-fluorouracil 400 mg/m^2 IV bolus followed by 600 mg/m^2 IV infusion over 22 hours on Days 1 and 2. Each cycle was 14 days.
Primary Outcome Measure Information:
Title
Progression-free Survival
Description
Progression-free survival (PFS), assessed by central radiological assessment, was defined as the time from randomization to disease progression per modified response evaluation criteria in solid tumors (RECIST) criteria or death. Participants who were alive but did not meet criteria for progression by the data cutoff date were censored at their last evaluable disease assessment date. Progressive disease is defined as a ≥ 20% increase in the size of target lesions or unequivocal progression of existing non-target lesions or any new lesions.
Time Frame
From randomization until the data cutoff date of 30 September 2008. Maximum follow-up time was 109 weeks.
Secondary Outcome Measure Information:
Title
Overall Survival
Description
The definition of overall survival is the time from randomization to death; participants who were alive at the analysis data cutoff were censored at their last contact date.
Time Frame
From randomization until the data cutoff date of 28 August 2009. Maximum time on follow-up was 153 weeks.
Title
Percentage of Participants With an Objective Response
Description
Participants were evaluated for tumor response per the modified Response Evaluation Criteria in Solid Tumors (RECIST) criteria every 8 weeks until disease progression. Objective response by central radiological assessment was defined as the incidence of either a confirmed complete or partial response (CR or PR) while on the first-line treatment, as determined by blinded independent central review and confirmed no less than 4-weeks after the criteria for response are first met. CR: Disappearance of all target and non-target lesions and no new lesions. PR: At least a 30% decrease in the sum of the longest diameter of target lesions and no progression of non-target or no new lesions, or, disappearance of all target lesions and the persistence of ≥ 1 non-target lesion not qualifying for either CR or progressive disease. Participants without a post-baseline assessment were considered non-responders.
Time Frame
Every 8 weeks until disease progression up to the data cut-off date of 30 September 2008; Maximum follow-up time was 109 weeks.
Title
Time to Progression
Description
Time to progression was defined as time from randomization date to date of disease progression per the modified RECIST criteria.
Time Frame
From randomization until the data cut-off date of 30 September 2008; Maximum follow-up time was 109 weeks.
Title
Duration of Response
Description
Duration of response was calculated only for those participants with a confirmed CR or PR, as the time from the first CR or PR (subsequently confirmed within no less than 4 weeks) to first observed disease progression per modified RECIST criteria, based on a blinded central review.
Time Frame
Every 8 weeks until disease progression up to the data cut-off date of 30 September 2008; Maximum follow-up time was 109 weeks.
Title
Number of Participants With Adverse Events (AEs)
Description
A serious adverse event (SAE) is defined as an AE that • is fatal • is life threatening • requires in-patient hospitalization or prolongation of existing hospitalization • results in persistent or significant disability/incapacity • is a congenital anomaly/birth defect • other significant medical hazard. The relationship of the adverse event to the study treatment was assessed by the Investigator by means of the question: "Is there a reasonable possibility that the event may have been caused by the study treatment?"
Time Frame
From randomization until the data cut-off date of 28 August 2009; Maximum time on follow-up was 153 weeks.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Man or woman at least 18 years old
Diagnosis of metastatic colorectal cancer
At least 1 uni-dimensionally measurable lesion of at least 20 mm per modified RECIST
Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
Paraffin-embedded tumor tissue from the primary tumor or metastasis available for central analyse Exclusion Criteria:
History or known presence of central nervous system (CNS) metastases
History of another primary cancer, except: Curatively treated in situ cervical cancer, or Curatively resected non-melanoma skin cancer, or Other primary solid tumor curatively treated with no known active disease present and no treatment administered for ≥ 5 years before randomization
Prior chemotherapy or systemic therapy for the treatment of metastatic colorectal carcinoma except: adjuvant fluoropyrimidine-based chemotherapy or prior fluoropyrimidine therapy administered solely for the purpose of radiosensitization
Prior oxaliplatin therapy
Prior anti-epidermal growth factor receptor (EGFr) antibody therapy (eg, cetuximab) or treatment with small molecule EGFr inhibitors (eg, erlotinib)
Clinically significant cardiovascular disease (including myocardial infarction, unstable angina, symptomatic congestive heart failure, serious uncontrolled cardiac arrhythmia) 1 year prior to randomization History of interstitial lung disease (eg, pneumonitis or pulmonary fibrosis) or evidence of interstitial lung disease on baseline chest computed tomography (CT) scan
Active inflammatory bowel disease or other bowel disease causing chronic diarrhea (defined as > Common terminology criteria (CTC) grade 2 [CTCAE version 3.0])
Peripheral sensory neuropathy with functional impairment
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
24024839
Citation
Douillard JY, Oliner KS, Siena S, Tabernero J, Burkes R, Barugel M, Humblet Y, Bodoky G, Cunningham D, Jassem J, Rivera F, Kocakova I, Ruff P, Blasinska-Morawiec M, Smakal M, Canon JL, Rother M, Williams R, Rong A, Wiezorek J, Sidhu R, Patterson SD. Panitumumab-FOLFOX4 treatment and RAS mutations in colorectal cancer. N Engl J Med. 2013 Sep 12;369(11):1023-34. doi: 10.1056/NEJMoa1305275.
Results Reference
background
PubMed Identifier
24718886
Citation
Douillard JY, Siena S, Cassidy J, Tabernero J, Burkes R, Barugel M, Humblet Y, Bodoky G, Cunningham D, Jassem J, Rivera F, Kocakova I, Ruff P, Blasinska-Morawiec M, Smakal M, Canon JL, Rother M, Oliner KS, Tian Y, Xu F, Sidhu R. Final results from PRIME: randomized phase III study of panitumumab with FOLFOX4 for first-line treatment of metastatic colorectal cancer. Ann Oncol. 2014 Jul;25(7):1346-1355. doi: 10.1093/annonc/mdu141. Epub 2014 Apr 8.
Results Reference
background
PubMed Identifier
20921465
Citation
Douillard JY, Siena S, Cassidy J, Tabernero J, Burkes R, Barugel M, Humblet Y, Bodoky G, Cunningham D, Jassem J, Rivera F, Kocakova I, Ruff P, Blasinska-Morawiec M, Smakal M, Canon JL, Rother M, Oliner KS, Wolf M, Gansert J. Randomized, phase III trial of panitumumab with infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX4) versus FOLFOX4 alone as first-line treatment in patients with previously untreated metastatic colorectal cancer: the PRIME study. J Clin Oncol. 2010 Nov 1;28(31):4697-705. doi: 10.1200/JCO.2009.27.4860. Epub 2010 Oct 4.
Results Reference
background
PubMed Identifier
25956209
Citation
Douillard JY, Siena S, Peeters M, Koukakis R, Terwey JH, Tabernero J. Impact of early tumour shrinkage and resection on outcomes in patients with wild-type RAS metastatic colorectal cancer. Eur J Cancer. 2015 Jul;51(10):1231-42. doi: 10.1016/j.ejca.2015.03.026. Epub 2015 May 5.
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
31378656
Citation
Abdel-Rahman O. Effect of Body Mass Index on 5-FU-Based Chemotherapy Toxicity and Efficacy Among Patients With Metastatic Colorectal Cancer; A Pooled Analysis of 5 Randomized Trials. Clin Colorectal Cancer. 2019 Dec;18(4):e385-e393. doi: 10.1016/j.clcc.2019.07.005. Epub 2019 Jul 15.
Results Reference
derived
PubMed Identifier
30679026
Citation
Abdel-Rahman O. Impact of Sex on Chemotherapy Toxicity and Efficacy Among Patients With Metastatic Colorectal Cancer: Pooled Analysis of 5 Randomized Trials. Clin Colorectal Cancer. 2019 Jun;18(2):110-115.e2. doi: 10.1016/j.clcc.2018.12.006. Epub 2018 Dec 28.
Results Reference
derived
PubMed Identifier
30614531
Citation
Modest DP, Rivera F, Bachet JB, de Braud F, Pietrantonio F, Koukakis R, Demonty G, Douillard JY. Panitumumab-based maintenance after oxaliplatin discontinuation in metastatic colorectal cancer: A retrospective analysis of two randomised trials. Int J Cancer. 2019 Jul 15;145(2):576-585. doi: 10.1002/ijc.32110. Epub 2019 Jan 24.
Results Reference
derived
PubMed Identifier
30019318
Citation
Udar N, Lofton-Day C, Dong J, Vavrek D, Jung AS, Meier K, Iyer A, Slaughter R, Gutekunst K, Bach BA, Peeters M, Douillard JY. Clinical validation of the next-generation sequencing-based Extended RAS Panel assay using metastatic colorectal cancer patient samples from the phase 3 PRIME study. J Cancer Res Clin Oncol. 2018 Oct;144(10):2001-2010. doi: 10.1007/s00432-018-2688-3. Epub 2018 Jul 17.
Results Reference
derived
PubMed Identifier
29627309
Citation
Boeckx N, Koukakis R, Op de Beeck K, Rolfo C, Van Camp G, Siena S, Tabernero J, Douillard JY, Andre T, Peeters M. Effect of Primary Tumor Location on Second- or Later-line Treatment Outcomes in Patients With RAS Wild-type Metastatic Colorectal Cancer and All Treatment Lines in Patients With RAS Mutations in Four Randomized Panitumumab Studies. Clin Colorectal Cancer. 2018 Sep;17(3):170-178.e3. doi: 10.1016/j.clcc.2018.03.005. Epub 2018 Mar 8.
Results Reference
derived
PubMed Identifier
28449055
Citation
Boeckx N, Koukakis R, Op de Beeck K, Rolfo C, Van Camp G, Siena S, Tabernero J, Douillard JY, Andre T, Peeters M. Primary tumor sidedness has an impact on prognosis and treatment outcome in metastatic colorectal cancer: results from two randomized first-line panitumumab studies. Ann Oncol. 2017 Aug 1;28(8):1862-1868. doi: 10.1093/annonc/mdx119.
Results Reference
derived
PubMed Identifier
27843597
Citation
Siena S, Tabernero J, Bodoky G, Cunningham D, Rivera F, Ruff P, Canon JL, Koukakis R, Demonty G, Hechmati G, Douillard JY. Quality of life during first-line FOLFOX4+/-panitumumab in RAS wild-type metastatic colorectal carcinoma: results from a randomised controlled trial. ESMO Open. 2016 Mar 31;1(2):e000041. doi: 10.1136/esmoopen-2016-000041. eCollection 2016.
Results Reference
derived
PubMed Identifier
26049686
Citation
Peeters M, Kafatos G, Taylor A, Gastanaga VM, Oliner KS, Hechmati G, Terwey JH, van Krieken JH. Prevalence of RAS mutations and individual variation patterns among patients with metastatic colorectal cancer: A pooled analysis of randomised controlled trials. Eur J Cancer. 2015 Sep;51(13):1704-13. doi: 10.1016/j.ejca.2015.05.017. Epub 2015 Jun 3.
Results Reference
derived
PubMed Identifier
22070868
Citation
Weeraratne D, Chen A, Pennucci JJ, Wu CY, Zhang K, Wright J, Perez-Ruixo JJ, Yang BB, Kaliyaperumal A, Gupta S, Swanson SJ, Chirmule N, Starcevic M. Immunogenicity of panitumumab in combination chemotherapy clinical trials. BMC Clin Pharmacol. 2011 Nov 9;11:17. doi: 10.1186/1472-6904-11-17.
Results Reference
derived
Links:
URL
http://www.amgentrials.com
Description
AmgenTrials clinical trials website
Learn more about this trial
PRIME: Panitumumab Randomized Trial In Combination With Chemotherapy for Metastatic Colorectal Cancer to Determine Efficacy
We'll reach out to this number within 24 hrs