Clinical trial NCT00819780: PEAK: Panitumumab Plus mFOLFOX6 vs. Bevacizumab Plus mFOLFOX6 for First Line Treatment of Metastatic Colorectal Cancer (mCRC) Patients With Wild-Type Kirsten Rat Sarcoma-2 Virus (KRAS) Tumors
Official title: A Randomized, Multicenter, Phase 2 Study to Compare the Efficacy of Panitumumab in Combination With mFOLFOX6 to the Efficacy of Bevacizumab in Combination With mFOLFOX6 in Patients With Previously Untreated, KRAS Wild-Type, Unresectable, Metastatic Colorectal Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Colon Cancer
Colorectal Cancer
Rectal Cancer
Metastatic Colorectal Cancer
Keywords: Colon Cancer
Colorectal Cancer
Rectal Cancer
Panitumumab
Vectibix
modified FOLFOX 6
mFOLFOX 6
FOLFOX
Bevacizumab
Avastin
First-Line
metastatic
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2009-01-09
Enrollment: 285
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Progression-free Survival (PFS)
timeFrame: From randomization until the data cutoff date of 30 May 2012; median follow-up time was 60 weeks.
Secondary outcomes:
measure: Overall Survival
timeFrame: From randomization until the data cutoff date of 30 May 2012; median follow-up time was 60 weeks.
measure: Percentage of Participants With an Objective Response
timeFrame: From randomization until the data cutoff date of 30 May 2012; median follow-up time was 60 weeks.
measure: Duration of Response
timeFrame: From randomization until the data cutoff date of 30 May 2012; median follow-up time was 60 weeks.
measure: Time to Disease Progression
timeFrame: From randomization until the data cutoff date of 30 May 2012; median follow-up time was 60 weeks.
measure: Time to Initial Objective Response
timeFrame: From randomization until the data cutoff date of 30 May 2012; median follow-up time was 60 weeks.
measure: Resection Rate
timeFrame: From randomization until the data cutoff date of 30 May 2012; median follow-up time was 60 weeks.
measure: Progression-free Survival (PFS) in Participants With Wild-type Rat Sarcoma Viral Oncogene Homolog (RAS)
timeFrame: From randomization until the data cutoff date of 30 May 2012; median follow-up time was 60 weeks.
measure: Progression-free Survival (PFS) in Participants With Wild-type RAS / V-raf Murine Sarcoma Viral Oncogene Homolog B1 (BRAF)
timeFrame: From randomization until the data cutoff date of 30 May 2012; median follow-up time was 60 weeks.
measure: Overall Survival in Participants With Wild-type RAS
timeFrame: From randomization until the data cutoff date of 30 May 2012; median follow-up time was 60 weeks.
measure: Overall Survival in Participants With Wild-type RAS / BRAF
timeFrame: From randomization until the data cutoff date of 30 May 2012; median follow-up time was 60 weeks.
measure: Percentage of Participants With an Objective Response for Participants With Wild-type RAS
timeFrame: From randomization until the data cutoff date of 30 May 2012; median follow-up time was 60 weeks.
measure: Percentage of Participants With an Objective Response for Participants With Wild-type RAS / BRAF
timeFrame: From randomization until the data cutoff date of 30 May 2012; median follow-up time was 60 weeks.
measure: Number of Participants With Adverse Events (AEs)
timeFrame: 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.
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Research Site
state: Alabama
city: Huntsville
country: United States
facility: Research Site
state: Alabama
city: Berkeley
country: United States
facility: Research Site
state: California
city: Beverly Hills
country: United States
facility: Research Site
state: California
city: Burbank
country: United States
facility: Research Site
state: California
city: Fountain Valley
country: United States
facility: Research Site
state: California
city: La Verne
country: United States
facility: Research Site
state: California
city: Orange
country: United States
facility: Research Site
state: California
city: Riverside
country: United States
facility: Research Site
state: California
city: Roseville
country: United States
facility: Research Site
state: California
city: Denver
country: United States
facility: Research Site
state: Colorado
city: Stamford
country: United States
facility: Research Site
state: Connecticut
city: Waterbury
country: United States
facility: Research Site
state: Connecticut
city: Boynton Beach
country: United States
facility: Research Site
state: Florida
city: Coral Springs
country: United States
facility: Research Site
state: Florida
city: Daytona Beach
country: United States
facility: Research Site
state: Florida
city: Hollywood
country: United States
facility: Research Site
state: Florida
city: Lake Worth
country: United States
facility: Research Site
state: Florida
city: Alpharetta
country: United States
facility: Research Site
state: Georgia
city: Augusta
country: United States
facility: Research Site
state: Georgia
city: Savannah
country: United States
facility: Research Site
state: Georgia
city: Post Falls
country: United States
facility: Research Site
state: Idaho
city: Gurnee
country: United States
facility: Research Site
state: Illinois
city: Peoria
country: United States
facility: Research Site
state: Illinois
city: Indianapolis
country: United States
facility: Research Site
state: Indiana
city: Overland Park
country: United States
facility: Research Site
state: Kansas
city: Wichita
country: United States
facility: Research Site
state: Kansas
city: Danville
country: United States
facility: Research Site
state: Kentucky
city: Hazard
country: United States
facility: Research Site
state: Kentucky
city: Paducah
country: United States
facility: Research Site
state: Kentucky
city: Baltimore
country: United States
facility: Research Site
state: Maryland
city: Bethesda
country: United States
facility: Research Site
state: Maryland
city: Boston
country: United States
facility: Research Site
state: Massachusetts
city: Kalamazoo
country: United States
facility: Research Site
state: Michigan
city: Lambertville
country: United States
facility: Research Site
state: Michigan
city: Lansing
country: United States
facility: Research Site
state: Michigan
city: Mountain Lakes
country: United States
facility: Research Site
state: New Jersey
city: Sparta
country: United States
facility: Research Site
state: New Jersey
city: Albuquerque
country: United States
facility: Research Site
state: New Mexico
city: Buffalo
country: United States
facility: Research Site
state: New York
city: East Setauket
country: United States
facility: Research Site
state: New York
city: Staten Island
country: United States
facility: Research Site
state: New York
city: Huntersville
country: United States
facility: Research Site
state: North Carolina
city: Raleigh
country: United States
facility: Research Site
state: North Carolina
city: Akron
country: United States
facility: Research Site
state: Ohio
city: Columbus
country: United States
facility: Research Site
state: Ohio
city: Hershey
country: United States
facility: Research Site
state: Pennsylvania
city: Philadelphia
country: United States
facility: Research Site
state: Pennsylvania
city: Greenville
country: United States
facility: Research Site
state: South Carolina
city: Mount Pleasant
country: United States
facility: Research Site
state: South Carolina
city: Memphis
country: United States
facility: Research Site
state: Tennessee
city: Austin
country: United States
facility: Research Site
state: Texas
city: Corpus Christi
country: United States
facility: Research Site
state: Texas
city: Dallas
country: United States
facility: Research Site
state: Texas
city: Round Rock
country: United States
facility: Research Site
state: Texas
city: Temple
country: United States
facility: Research Site
state: Texas
city: Tyler
country: United States
facility: Research Site
state: Texas
city: White River Junction
country: United States
facility: Research Site
state: Vermont
city: Chesapeake
country: United States
facility: Research Site
state: Virginia
city: Newport News
country: United States
facility: Research Site
state: Virginia
city: Newport News
country: United States
facility: Research Site
state: Virginia
city: Spokane
country: United States
facility: Research Site
state: Washington
city: Vancouver
country: United States
facility: Research Site
state: Washington
city: Charleroi
country: Belgium
facility: Research Site
city: Edegem
country: Belgium
facility: Research Site
city: Libramont
country: Belgium
facility: Research Site
city: Sint-Niklaas
country: Belgium
facility: Research Site
city: Calgary
country: Canada
facility: Research Site
state: Alberta
city: Edmonton
country: Canada
facility: Research Site
state: Alberta
city: Vancouver
country: Canada
facility: Research Site
state: British Columbia
city: Victoria
country: Canada
facility: Research Site
state: British Columbia
city: Oshawa
country: Canada
facility: Research Site
state: Ontario
city: Greenfield Park
country: Canada
facility: Research Site
state: Quebec
city: Montreal
country: Canada
facility: Research Site
state: Quebec
city: Quebec
country: Canada
facility: Research Site
city: Berlin
country: Germany
facility: Research Site
city: Bielefeld
country: Germany
facility: Research Site
city: Magdeburg
country: Germany
facility: Research Site
city: MÃ¼nchen
country: Germany
facility: Research Site
city: MÃ¼nchen
country: Germany
facility: Research Site
city: Passau
country: Germany
facility: Research Site
city: Regensburg
country: Germany
facility: Research Site
city: WÃ¼rzburg
country: Germany
facility: Research Site
city: Alba (CN)
country: Italy
facility: Research Site
city: Fano
country: Italy
facility: Research Site
city: Genova
country: Italy
facility: Research Site
city: Mantova
country: Italy
facility: Research Site
city: Udine
country: Italy
facility: Research Site
city: Varese
country: Italy
facility: Research Site
city: MÃ¡laga
country: Spain
facility: Research Site
state: AndalucÃ-a
city: Santander
country: Spain
facility: Research Site
state: Cantabria
city: Sabadell
country: Spain
facility: Research Site
state: CataluÃ±a
city: Elche
country: Spain
facility: Research Site
state: Comunidad
city: A CoruÃ±a
country: Spain
facility: Research Site
state: Galicia
city: San SebastiÃ¡n De Los Reyes
country: Spain
facility: Research Site
state: Madrid
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References:
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.