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

NCT00819780 | Completed Phase 2 Results

• 1 other identifier: 20070509
• Study Type: interventional
• Target: 285
• Locations: 6 countries
• Sites: 95

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.

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

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (13)

• Overall Survival

  From randomization until the data cutoff date of 30 May 2012; median follow-up time was 60 weeks.

• Percentage of Participants With an Objective Response

  From randomization until the data cutoff date of 30 May 2012; median follow-up time was 60 weeks.

• Duration of Response

  From randomization until the data cutoff date of 30 May 2012; median follow-up time was 60 weeks.

• Time to Disease Progression

  From randomization until the data cutoff date of 30 May 2012; median follow-up time was 60 weeks.

• Time to Initial Objective Response

  From randomization until the data cutoff date of 30 May 2012; median follow-up time was 60 weeks.

Study Arms (2)

Panitumumab Plus mFOLFOX6

EXPERIMENTAL

Participants received 6 mg/kg panitumumab administered by intravenous (IV) infusion and modified FOLFOX6 (mFOLFOX6) chemotherapy regimen consisting of oxaliplatin (85 mg/m\^2), leucovorin (400 mg/m\^2) and 5-fluorouracil (5-FU) (2400 mg/m\^2) administered on Day 1 of every 14-day cycle until disease progression, unacceptable toxicity, withdrawal of consent, or death.

Drug: Panitumumab; Drug: mFOLFOX6

Bevacizumab Plus mFOLFOX6

ACTIVE COMPARATOR

Participants received 5 mg/kg bevacizumab administered by IV infusion and the mFOLFOX6 regimen consisting of oxaliplatin (85 mg/m\^2), leucovorin (400 mg/m\^2), followed by 5-FU (2400 mg/m\^2) administered on Day 1 of every 14-day cycle until disease progression, unacceptable toxicity, withdrawal of consent, or death.

Drug: Bevacizumab; Drug: mFOLFOX6

Interventions

Panitumumab DRUG

Panitumumab is a fully human immunoglobulin G (IgG)2 monoclonal antibody antagonist directed against human Epidermal Growth Factor receptor (EGFr).

Also known as: Vectibix

Panitumumab Plus mFOLFOX6

Bevacizumab DRUG

Bevacizumab is a humanized monoclonal IgG1 antibody that is directed against Vascular Endothelial Growth Factor (VEGF).

Also known as: Avastin

Bevacizumab Plus mFOLFOX6

mFOLFOX6 DRUG

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.

Bevacizumab Plus mFOLFOX6; Panitumumab Plus mFOLFOX6

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Amgen: lead

Study Sites (95)

Research Site

Birmingham, Alabama, 35205, United States

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Huntsville, Alabama, 35805, United States

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Berkeley, California, 94704, United States

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Beverly Hills, California, 90211, United States

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Burbank, California, 91505, United States

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Fountain Valley, California, 92708, United States

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La Verne, California, 91750, United States

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Orange, California, 92868, United States

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Riverside, California, 92501, United States

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Roseville, California, 95661, United States

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Denver, Colorado, 80218, United States

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Stamford, Connecticut, 06902, United States

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Waterbury, Connecticut, 06708, United States

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Boynton Beach, Florida, 33435, United States

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Coral Springs, Florida, 33065, United States

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Daytona Beach, Florida, 32114, United States

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Hollywood, Florida, 33021, United States

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Lake Worth, Florida, 33467, United States

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Alpharetta, Georgia, 30005, United States

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Augusta, Georgia, 30901, United States

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Savannah, Georgia, 31405, United States

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Post Falls, Idaho, 83854, United States

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Gurnee, Illinois, 60031, United States

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Peoria, Illinois, 61615, United States

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Indianapolis, Indiana, 46237, United States

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Overland Park, Kansas, 66210, United States

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Wichita, Kansas, 67214, United States

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Danville, Kentucky, 40422, United States

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Hazard, Kentucky, 41701, United States

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Paducah, Kentucky, 42003, United States

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Baltimore, Maryland, 21204, United States

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Bethesda, Maryland, 20817, United States

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Boston, Massachusetts, 02111, United States

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Kalamazoo, Michigan, 49048, United States

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Lambertville, Michigan, 48144, United States

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Lansing, Michigan, 48912, United States

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Mountain Lakes, New Jersey, 07046, United States

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Sparta, New Jersey, 07871, United States

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Albuquerque, New Mexico, 87131, United States

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Buffalo, New York, 14215, United States

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East Setauket, New York, 11733, United States

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Staten Island, New York, 10301, United States

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Huntersville, North Carolina, 28078, United States

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Raleigh, North Carolina, 27607, United States

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Akron, Ohio, 44304, United States

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Columbus, Ohio, 43228, United States

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Hershey, Pennsylvania, 17033, United States

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Philadelphia, Pennsylvania, 19106, United States

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Greenville, South Carolina, 29605, United States

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Mt. Pleasant, South Carolina, 29464, United States

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Memphis, Tennessee, 38120, United States

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Austin, Texas, 78759, United States

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Corpus Christi, Texas, 78463, United States

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Dallas, Texas, 75231, United States

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Round Rock, Texas, 78665, United States

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Temple, Texas, 76508, United States

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Tyler, Texas, 75702, United States

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White River Junction, Vermont, 05009, United States

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Chesapeake, Virginia, 23320, United States

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Newport News, Virginia, 23601, United States

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Newport News, Virginia, 23606, United States

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Spokane, Washington, 99218, United States

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Vancouver, Washington, 98684, United States

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Charleroi, 6000, Belgium

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Edegem, 2650, Belgium

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Libramont, 6800, Belgium

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Sint-Niklaas, 9100, Belgium

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Calgary, Alberta, T2N 4N2, Canada

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Edmonton, Alberta, T6G 1Z2, Canada

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Vancouver, British Columbia, V5Z 4E6, Canada

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Victoria, British Columbia, V8R 6V5, Canada

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Oshawa, Ontario, L1G 2B9, Canada

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Greenfield Park, Quebec, J4V 2H1, Canada

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Montreal, Quebec, H2X 3J4, Canada

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Québec, Quebec, G1R 2J6, Canada

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Berlin, 13125, Germany

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Bielefeld, 33611, Germany

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Magdeburg, 39104, Germany

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München, 81737, Germany

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München, 81925, Germany

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Passau, 94032, Germany

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Regensburg, 93049, Germany

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Würzburg, 97070, Germany

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Alba (CN), 12051, Italy

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Fano, 61032, Italy

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Genova, 16132, Italy

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Mantova, 46100, Italy

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Udine, 33100, Italy

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Varese, 21100, Italy

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Málaga, AndalucÃ-a, 29010, Spain

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Santander, Cantabria, 39008, Spain

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Sabadell, Cataluña, 08208, Spain

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Elche, Comunidad, 03203, Spain

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A Coruña, Galicia, 15006, Spain

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San Sebastián de Los Reyes, Madrid, 28702, Spain

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Related Publications (12)

• 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.

  PMID: 28424871 BACKGROUND

• 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.

  PMID: 24687833 BACKGROUND

• 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.

  PMID: 28449055 BACKGROUND

• 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.

  PMID: 27592068 BACKGROUND

• 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.

  PMID: 30614531 BACKGROUND

• 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.

  PMID: 29531837 BACKGROUND

• 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.

  PMID: 31515083 BACKGROUND

• 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.

  PMID: 29080924 BACKGROUND

• 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.

  PMID: 29627309 BACKGROUND

• 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.

  PMID: 30013091 BACKGROUND

• 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.

  PMID: 34172397 BACKGROUND

• 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.

  PMID: 26049686 DERIVED

Related Links

• AmgenTrials clinical trials website

MeSH Terms

Conditions

Colonic Neoplasms; Colorectal Neoplasms; Rectal Neoplasms; Neoplasm Metastasis

Interventions

Panitumumab; Bevacizumab

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Study Director
• Organization: Amgen Inc.

866-572-6436

Study Officials

• MD

  Amgen

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 6, 2008
• First Posted: January 9, 2009
• Study Start: April 24, 2009
• Primary Completion: May 30, 2012
• Study Completion: July 7, 2016
• Last Updated: December 6, 2022
• Results First Posted: August 6, 2014

Record last verified: 2022-11

Locations

US (63); BE (4); DE (8); IT (6); CA (8); ES (6)