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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT00819780
Other study ID # 20070509
Secondary ID
Status Completed
Phase Phase 2
First received
Last updated
Start date April 24, 2009
Est. completion date July 7, 2016

Study information

Verified date November 2022
Source Amgen
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

The primary objective of this study is to estimate the treatment effect on progression-free survival (PFS) of panitumumab relative to bevacizumab in combination with mFOLFOX6 chemotherapy as first-line therapy in patients with tumors expressing wild-type KRAS, unresectable mCRC.


Recruitment information / eligibility

Status Completed
Enrollment 285
Est. completion date July 7, 2016
Est. primary completion date May 30, 2012
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility Inclusion Criteria: - Histologically or cytologically-confirmed adenocarcinoma of the colon or rectum in patients with unresectable metastatic (M1) disease - Patients with at least 1 uni-dimensionally measurable lesion of at least 10 mm per modified Response Evaluation Criteria in Solid Tumors (RECIST) guidelines - Wild-type KRAS tumor status confirmed by an Amgen approved central laboratory or an experienced laboratory (local laboratory) per local regulatory guidelines using a validated test method - Eastern Cooperative Oncology Group (ECOG) score of 0 or 1 - Men or women 18 years of age or older - Adequate hematologic, renal, hepatic, metabolic, and coagulation function Exclusion Criteria: - History of prior or concurrent central nervous system (CNS) metastases - Prior chemotherapy or other systemic anticancer therapy for treatment of metastatic colorectal carcinoma - Clinically significant cardiac disease - Clinically significant peripheral sensory neuropathy - Active inflammatory bowel disease - Recent gastroduodenal ulcer to be active or uncontrolled - History of interstitial lung disease - Recent pulmonary embolism, deep vein thrombosis, or other significant venous event - Pre-existing bleeding diathesis and/or coagulopathy with exception of well-controlled anticoagulation therapy - Recent major surgical procedure, open biopsy, or significant traumatic injury not yet recovered from prior major surgery.

Study Design


Intervention

Drug:
Panitumumab
Panitumumab is a fully human immunoglobulin G (IgG)2 monoclonal antibody antagonist directed against human Epidermal Growth Factor receptor (EGFr).
Bevacizumab
Bevacizumab is a humanized monoclonal IgG1 antibody that is directed against Vascular Endothelial Growth Factor (VEGF).
mFOLFOX6
mFOLFOX6 regimen is a combination therapy of oxaliplatin (85 mg/m^2) administered as a 2-hour infusion on Day 1; leucovorin (400 mg/m^2) administered as a 2-hour infusion on Day 1; followed by a loading dose of 5-fluorouracil (5-FU; 400 mg/m^2) IV bolus administered over approximately 2 to 4 minutes on Day 1, then 5- FU (2400 mg/m^2) via ambulatory pump administered for a period of 46 to 48 hours.

Locations

Country Name City State
Belgium Research Site Charleroi
Belgium Research Site Edegem
Belgium Research Site Libramont
Belgium Research Site Sint-Niklaas
Canada Research Site Calgary Alberta
Canada Research Site Edmonton Alberta
Canada Research Site Greenfield Park Quebec
Canada Research Site Montreal Quebec
Canada Research Site Oshawa Ontario
Canada Research Site Quebec
Canada Research Site Vancouver British Columbia
Canada Research Site Victoria British Columbia
Germany Research Site Berlin
Germany Research Site Bielefeld
Germany Research Site München
Germany Research Site München
Germany Research Site Magdeburg
Germany Research Site Passau
Germany Research Site Regensburg
Germany Research Site Würzburg
Italy Research Site Alba (CN)
Italy Research Site Fano
Italy Research Site Genova
Italy Research Site Mantova
Italy Research Site Udine
Italy Research Site Varese
Spain Research Site A Coruña Galicia
Spain Research Site Elche Comunidad
Spain Research Site Málaga AndalucÃ-a
Spain Research Site Sabadell Cataluña
Spain Research Site San Sebastián De Los Reyes Madrid
Spain Research Site Santander Cantabria
United States Research Site Akron Ohio
United States Research Site Albuquerque New Mexico
United States Research Site Alpharetta Georgia
United States Research Site Augusta Georgia
United States Research Site Austin Texas
United States Research Site Baltimore Maryland
United States Research Site Berkeley California
United States Research Site Bethesda Maryland
United States Research Site Beverly Hills California
United States Research Site Birmingham Alabama
United States Research Site Boston Massachusetts
United States Research Site Boynton Beach Florida
United States Research Site Buffalo New York
United States Research Site Burbank California
United States Research Site Chesapeake Virginia
United States Research Site Columbus Ohio
United States Research Site Coral Springs Florida
United States Research Site Corpus Christi Texas
United States Research Site Dallas Texas
United States Research Site Danville Kentucky
United States Research Site Daytona Beach Florida
United States Research Site Denver Colorado
United States Research Site East Setauket New York
United States Research Site Fountain Valley California
United States Research Site Greenville South Carolina
United States Research Site Gurnee Illinois
United States Research Site Hazard Kentucky
United States Research Site Hershey Pennsylvania
United States Research Site Hollywood Florida
United States Research Site Huntersville North Carolina
United States Research Site Huntsville Alabama
United States Research Site Indianapolis Indiana
United States Research Site Kalamazoo Michigan
United States Research Site La Verne California
United States Research Site Lake Worth Florida
United States Research Site Lambertville Michigan
United States Research Site Lansing Michigan
United States Research Site Memphis Tennessee
United States Research Site Mount Pleasant South Carolina
United States Research Site Mountain Lakes New Jersey
United States Research Site Newport News Virginia
United States Research Site Newport News Virginia
United States Research Site Orange California
United States Research Site Overland Park Kansas
United States Research Site Paducah Kentucky
United States Research Site Peoria Illinois
United States Research Site Philadelphia Pennsylvania
United States Research Site Post Falls Idaho
United States Research Site Raleigh North Carolina
United States Research Site Riverside California
United States Research Site Roseville California
United States Research Site Round Rock Texas
United States Research Site Savannah Georgia
United States Research Site Sparta New Jersey
United States Research Site Spokane Washington
United States Research Site Stamford Connecticut
United States Research Site Staten Island New York
United States Research Site Temple Texas
United States Research Site Tyler Texas
United States Research Site Vancouver Washington
United States Research Site Waterbury Connecticut
United States Research Site White River Junction Vermont
United States Research Site Wichita Kansas

Sponsors (1)

Lead Sponsor Collaborator
Amgen

Countries where clinical trial is conducted

United States,  Belgium,  Canada,  Germany,  Italy,  Spain, 

References & Publications (11)

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. — View 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. — View Citation

Heinemann V, Rivera F, O'Neil BH, Stintzing S, Koukakis R, Terwey JH, Douillard JY. A study-level meta-analysis of efficacy data from head-to-head first-line trials of epidermal growth factor receptor inhibitors versus bevacizumab in patients with RAS wild-type metastatic colorectal cancer. Eur J Cancer. 2016 Nov;67:11-20. doi: 10.1016/j.ejca.2016.07.019. Epub 2016 Sep 1. — View 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. — View Citation

Peeters M, Forget F, Karthaus M, Valladares-Ayerbes M, Zaniboni A, Demonty G, Guan X, Rivera F. Exploratory pooled analysis evaluating the effect of sequence of biological therapies on overall survival in patients with RAS wild-type metastatic colorectal carcinoma. ESMO Open. 2018 Feb 24;3(2):e000297. doi: 10.1136/esmoopen-2017-000297. eCollection 2018. — View Citation

Peeters M, Price T, Taieb J, Geissler M, Rivera F, Canon JL, Pentheroudakis G, Koukakis R, Burdon P, Siena S. Relationships between tumour response and primary tumour location, and predictors of long-term survival, in patients with RAS wild-type metastatic colorectal cancer receiving first-line panitumumab therapy: retrospective analyses of the PRIME and PEAK clinical trials. Br J Cancer. 2018 Aug;119(3):303-312. doi: 10.1038/s41416-018-0165-z. Epub 2018 Jul 17. — View Citation

Rivera F, Karthaus M, Hecht JR, Sevilla I, Forget F, Fasola G, Canon JL, Guan X, Demonty G, Schwartzberg LS. Final analysis of the randomised PEAK trial: overall survival and tumour responses during first-line treatment with mFOLFOX6 plus either panitumumab or bevacizumab in patients with metastatic colorectal carcinoma. Int J Colorectal Dis. 2017 Aug;32(8):1179-1190. doi: 10.1007/s00384-017-2800-1. Epub 2017 Apr 19. — View Citation

Sartore-Bianchi A, Garcia-Alfonso P, Geissler M, Kohne CH, Peeters M, Price T, Valladares-Ayerbes M, Zhang Y, Burdon P, Taieb J, Modest DP. Relationships Between Kohne Category/Baseline Tumor Load and Early Tumor Shrinkage, Depth of Response, and Outcomes in Metastatic Colorectal Cancer. Clin Colorectal Cancer. 2021 Dec;20(4):305-313. doi: 10.1016/j.clcc.2021.05.007. Epub 2021 May 25. — View Citation

Schwartzberg LS, Rivera F, Karthaus M, Fasola G, Canon JL, Hecht JR, Yu H, Oliner KS, Go WY. PEAK: a randomized, multicenter phase II study of panitumumab plus modified fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) or bevacizumab plus mFOLFOX6 in patients with previously untreated, unresectable, wild-type KRAS exon 2 metastatic colorectal cancer. J Clin Oncol. 2014 Jul 20;32(21):2240-7. doi: 10.1200/JCO.2013.53.2473. Epub 2014 Mar 31. — View 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. — View Citation

Taieb J, Rivera F, Siena S, Karthaus M, Valladares-Ayerbes M, Gallego J, Geissler M, Koukakis R, Demonty G, Peeters M. Exploratory analyses assessing the impact of early tumour shrinkage and depth of response on survival outcomes in patients with RAS wild-type metastatic colorectal cancer receiving treatment in three randomised panitumumab trials. J Cancer Res Clin Oncol. 2018 Feb;144(2):321-335. doi: 10.1007/s00432-017-2534-z. Epub 2017 Oct 28. Erratum In: J Cancer Res Clin Oncol. 2018 Feb 15;: — View Citation

* Note: There are 11 references in allClick here to view all references

Outcome

Type Measure Description Time frame Safety issue
Primary Progression-free Survival (PFS) PFS was defined as the time from the date of randomization to the date of first disease progression, or death within 60 days after the last evaluable tumor assessment or randomization date (whichever was later). Participants not meeting the criteria by the cutoff date were censored at the last evaluable tumor assessment date. Tumor response was evaluated by the investigator per modified Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0 every 8 weeks until radiographic disease progression. Progression is defined as at least a 20% increase in the size of target lesions, unequivocal progression of existing non-target lesions, or any new lesions. From randomization until the data cutoff date of 30 May 2012; median follow-up time was 60 weeks.
Secondary Overall Survival Overall survival was defined as the time from randomization to the date of death, with participants alive or lost to follow-up at the analysis data cutoff date censored at their last contact date. From randomization until the data cutoff date of 30 May 2012; median follow-up time was 60 weeks.
Secondary Percentage of Participants With an Objective Response Objective response was defined as having a confirmed complete response (CR) or partial response (PR) during first-line treatment, based on the investigator's review of scans using a modified-RECIST v1.0. A complete or partial response was confirmed no less than 4-weeks after the criteria for response were first met. Complete Response: Disappearance of all target and non-target lesions and no new lesions. Partial Response: At least a 30% decrease in the sum of the longest diameter (SLD) of target lesions and no progression of non-target lesions and no new lesions, or the disappearance of all target lesions with persistence of one or more non-target lesion(s) not qualifying for either CR or progressive disease and no new lesions. From randomization until the data cutoff date of 30 May 2012; median follow-up time was 60 weeks.
Secondary Duration of Response For participants with a confirmed objective response, the time from first confirmed objective response to radiologic disease progression per modified RECIST 1.0 criteria or death. For participants who responded and have not progressed or died, duration of response was censored at their last evaluable disease assessment date. From randomization until the data cutoff date of 30 May 2012; median follow-up time was 60 weeks.
Secondary Time to Disease Progression Time to progression (TTP) is defined as the time from randomization to the date of radiologic disease progression per modified RECIST 1.0 criteria. Participants not meeting criteria for disease progression by the analysis data cutoff date were censored at their last evaluable disease assessment date. Progression is defined as at least a 20% increase in the size of target lesions, unequivocal progression of existing non-target lesions, or any new lesions. From randomization until the data cutoff date of 30 May 2012; median follow-up time was 60 weeks.
Secondary Time to Initial Objective Response For participants with a confirmed objective response, the time from randomization to the date of first confirmed objective response. Assessments are based on the investigator's review of scans using a modified-RECIST v1.0. An objective response is defined as a best tumor response of complete or partial response. A complete or partial response was confirmed no less than 4-weeks after the criteria for response were first met. From randomization until the data cutoff date of 30 May 2012; median follow-up time was 60 weeks.
Secondary Resection Rate The resection rate was defined as the percentage of participants with a surgical procedure that resulted in partial reduction or complete eradication of all metastatic disease. From randomization until the data cutoff date of 30 May 2012; median follow-up time was 60 weeks.
Secondary Progression-free Survival (PFS) in Participants With Wild-type Rat Sarcoma Viral Oncogene Homolog (RAS) PFS was defined as the time from the date of randomization to the date of first disease progression, or death within 60 days after the last evaluable tumor assessment or randomization date (whichever was later). Participants not meeting the criteria by the cutoff date were censored at the last evaluable tumor assessment date. Tumor response was evaluated by the investigator per modified Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0 every 8 weeks until radiographic disease progression. Progression is defined as at least a 20% increase in the size of target lesions, unequivocal progression of existing non-target lesions, or any new lesions. From randomization until the data cutoff date of 30 May 2012; median follow-up time was 60 weeks.
Secondary Progression-free Survival (PFS) in Participants With Wild-type RAS / V-raf Murine Sarcoma Viral Oncogene Homolog B1 (BRAF) PFS was defined as the time from the date of randomization to the date of first disease progression, or death within 60 days after the last evaluable tumor assessment or randomization date (whichever was later). Participants not meeting the criteria by the cutoff date were censored at the last evaluable tumor assessment date. Tumor response was evaluated by the investigator per modified Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0 every 8 weeks until radiographic disease progression. Progression is defined as at least a 20% increase in the size of target lesions, unequivocal progression of existing non-target lesions, or any new lesions. From randomization until the data cutoff date of 30 May 2012; median follow-up time was 60 weeks.
Secondary Overall Survival in Participants With Wild-type RAS Overall survival was defined as the time from randomization to the date of death, with participants alive or lost to follow-up at the analysis data cutoff date censored at their last contact date. From randomization until the data cutoff date of 30 May 2012; median follow-up time was 60 weeks.
Secondary Overall Survival in Participants With Wild-type RAS / BRAF Overall survival was defined as the time from randomization to the date of death, with participants alive or lost to follow-up at the analysis data cutoff date censored at their last contact date. From randomization until the data cutoff date of 30 May 2012; median follow-up time was 60 weeks.
Secondary Percentage of Participants With an Objective Response for Participants With Wild-type RAS Objective response was defined as having a confirmed complete response (CR) or partial response (PR) during first-line treatment, based on the investigator's review of scans using a modified-RECIST v1.0. A complete or partial response was confirmed no less than 4-weeks after the criteria for response were first met.
Complete Response: Disappearance of all target and non-target lesions and no new lesions. Partial Response: At least a 30% decrease in the sum of the longest diameter (SLD) of target lesions and no progression of non-target lesions and no new lesions, or the disappearance of all target lesions with persistence of one or more non-target lesion(s) not qualifying for either CR or progressive disease and no new lesions.
From randomization until the data cutoff date of 30 May 2012; median follow-up time was 60 weeks.
Secondary Percentage of Participants With an Objective Response for Participants With Wild-type RAS / BRAF Objective response was defined as having a confirmed complete response (CR) or partial response (PR) during first-line treatment, based on the investigator's review of scans using a modified-RECIST v1.0. A complete or partial response was confirmed no less than 4-weeks after the criteria for response were first met. Complete Response: Disappearance of all target and non-target lesions and no new lesions. Partial Response: At least a 30% decrease in the sum of the longest diameter (SLD) of target lesions and no progression of non-target lesions and no new lesions, or the disappearance of all target lesions with persistence of one or more non-target lesion(s) not qualifying for either CR or progressive disease and no new lesions. From randomization until the data cutoff date of 30 May 2012; median follow-up time was 60 weeks.
Secondary Number of Participants With Adverse Events (AEs) Severity was graded using Common Terminology Criteria for Adverse Events (CTCAE) v3.0, with the exception of some dermatology/skin adverse events that were graded using CTCAE v3.0 with modifications. Fatal adverse events are classified as grade 5. Serious adverse events include any event that is fatal, life threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, a congenital anomaly/birth defect, or other significant medical hazard. Treatment-related AEs were those that the investigator considered a reasonable possibility that might have been caused by study drug. The time frame for adverse event reporting is from the first dose date to 30 days since the last dose date. The median time frame is 8.0 months for Panitumumab Plus mFOLFOX arm and 7.3 months for Bevacizumab Plus mFOLFOX6 arm.
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