Colon CancerPhase 2NCT00819780
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
A Phase 2 study testing Panitumumab, Bevacizumab and mFOLFOX6 in people with Colon Cancer and Colorectal Cancer, run by Amgen at 95 sites in 6 countries.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Colon Cancer, Colorectal Cancer, Rectal Cancer
- What is being tested?
- Panitumumab, Bevacizumab and mFOLFOX6
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 285 participants
- Where
- 95 sitesin 6 countries
- Study dates
- 24 Apr 2009to 7 Jul 2016
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 10Show fewer
- 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.
Trial locations and contacts
95 sites in 6 countries.
95 sites in 6 countries
United States63 sites
Research Site
Akron, Ohio, 44304
Research Site
Albuquerque, New Mexico, 87131
Research Site
Alpharetta, Georgia, 30005
Research Site
Augusta, Georgia, 30901
Research Site
Austin, Texas, 78759
Research Site
Baltimore, Maryland, 21204
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Berkeley, California, 94704
Research Site
Bethesda, Maryland, 20817
Research Site
Beverly Hills, California, 90211
Research Site
Birmingham, Alabama, 35205
Research Site
Boston, Massachusetts, 02111
Research Site
Boynton Beach, Florida, 33435
Research Site
Buffalo, New York, 14215
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Burbank, California, 91505
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Chesapeake, Virginia, 23320
Research Site
Columbus, Ohio, 43228
Research Site
Coral Springs, Florida, 33065
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Corpus Christi, Texas, 78463
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Dallas, Texas, 75231
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Danville, Kentucky, 40422
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Daytona Beach, Florida, 32114
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Denver, Colorado, 80218
Research Site
East Setauket, New York, 11733
Research Site
Fountain Valley, California, 92708
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Greenville, South Carolina, 29605
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Gurnee, Illinois, 60031
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Hazard, Kentucky, 41701
Research Site
Hershey, Pennsylvania, 17033
Research Site
Hollywood, Florida, 33021
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Huntersville, North Carolina, 28078
Research Site
Huntsville, Alabama, 35805
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Indianapolis, Indiana, 46237
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Kalamazoo, Michigan, 49048
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La Verne, California, 91750
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Lake Worth, Florida, 33467
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Lambertville, Michigan, 48144
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Lansing, Michigan, 48912
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Memphis, Tennessee, 38120
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Mountain Lakes, New Jersey, 07046
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Mt. Pleasant, South Carolina, 29464
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Newport News, Virginia, 23601
Research Site
Newport News, Virginia, 23606
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Orange, California, 92868
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Overland Park, Kansas, 66210
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Paducah, Kentucky, 42003
Research Site
Peoria, Illinois, 61615
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Philadelphia, Pennsylvania, 19106
Research Site
Post Falls, Idaho, 83854
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Raleigh, North Carolina, 27607
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Riverside, California, 92501
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Roseville, California, 95661
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Round Rock, Texas, 78665
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Savannah, Georgia, 31405
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Sparta, New Jersey, 07871
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Spokane, Washington, 99218
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Stamford, Connecticut, 06902
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Staten Island, New York, 10301
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Temple, Texas, 76508
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Tyler, Texas, 75702
Research Site
Vancouver, Washington, 98684
Research Site
Waterbury, Connecticut, 06708
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White River Junction, Vermont, 05009
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Wichita, Kansas, 67214
Canada8 sites
Research Site
Calgary, Alberta, T2N 4N2
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Edmonton, Alberta, T6G 1Z2
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Greenfield Park, Quebec, J4V 2H1
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Montreal, Quebec, H2X 3J4
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Oshawa, Ontario, L1G 2B9
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Québec, Quebec, G1R 2J6
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Vancouver, British Columbia, V5Z 4E6
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Victoria, British Columbia, V8R 6V5
Germany8 sites
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Berlin, 13125
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Bielefeld, 33611
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München, 81737
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München, 81925
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Magdeburg, 39104
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Passau, 94032
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Regensburg, 93049
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Würzburg, 97070
Italy6 sites
Research Site
Alba (CN), 12051
Research Site
Fano, 61032
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Genova, 16132
Research Site
Mantua, 46100
Research Site
Udine, 33100
Research Site
Varese, 21100
Spain6 sites
Research Site
A Coruña, Galicia, 15006
Research Site
Elche, Comunidad, 03203
Research Site
Málaga, AndalucÃ-a, 29010
Research Site
Sabadell, Cataluña, 08208
Research Site
San Sebastián de Los Reyes, Madrid, 28702
Research Site
Santander, Cantabria, 39008
Belgium4 sites
Research Site
Charleroi, 6000
Research Site
Edegem, 2650
Research Site
Libramont, 6800
Research Site
Sint-Niklaas, 9100
About this study
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
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.
- Being tested
- Panitumumab, Bevacizumab, mFOLFOX6
- Keywords
- Colon Cancer, Colorectal Cancer, Rectal Cancer, Panitumumab, Vectibix, modified FOLFOX 6, mFOLFOX 6, FOLFOX, Bevacizumab, Avastin, First-Line, metastatic
- Medical subject headings
- Colonic Neoplasms, Colorectal Neoplasms, Rectal Neoplasms, Neoplasm Metastasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PanitumumabDrug
Also called Vectibix
Panitumumab is a fully human immunoglobulin G (IgG)2 monoclonal antibody antagonist directed against human Epidermal Growth Factor receptor (EGFr).
BevacizumabDrug
Also called Avastin
Bevacizumab is a humanized monoclonal IgG1 antibody that is directed against Vascular Endothelial Growth Factor (VEGF).
mFOLFOX6Drug
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Bevacizumab; Drug: mFOLFOX6 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: From randomization until the data cutoff date of 30 May 2012; median follow-up time was 60 weeks.
Secondary outcomes (13)
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.
Measured: 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
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.
Measured: From randomization until the data cutoff date of 30 May 2012; median follow-up time was 60 weeks.
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.
Measured: From randomization until the data cutoff date of 30 May 2012; median follow-up time was 60 weeks.
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.
Measured: From randomization until the data cutoff date of 30 May 2012; median follow-up time was 60 weeks.
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.
Measured: From randomization until the data cutoff date of 30 May 2012; median follow-up time was 60 weeks.
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.
Measured: From randomization until the data cutoff date of 30 May 2012; median follow-up time was 60 weeks.
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.
Measured: From randomization until the data cutoff date of 30 May 2012; median follow-up time was 60 weeks.
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.
Measured: From randomization until the data cutoff date of 30 May 2012; median follow-up time was 60 weeks.
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.
Measured: From randomization until the data cutoff date of 30 May 2012; median follow-up time was 60 weeks.
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.
Measured: 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 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.
Measured: 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 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.
Measured: From randomization until the data cutoff date of 30 May 2012; median follow-up time was 60 weeks.
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.
Measured: 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.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Jan 2009 (estimated)
- Study start24 Apr 2009
- Primary completion30 May 2012
- Study completion7 Jul 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (12)Papers the sponsor has linked to this study.
- Other trials for Colon CancerStudies of the same condition, open and under way.
- More trials run by AmgenThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 285 participants (actual)
Sponsor and investigators
- Lead sponsor
- Amgen
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- MD, Study director, Amgen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00819780
- Sponsor's protocol ID
- 20070509
- Status last verified
- Nov 2022
- First submitted
- 6 Nov 2008
- Last updated
- 6 Dec 2022
- Results posted
- Yes, on ClinicalTrials.gov
Publications
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.
PubMed 28424871Schwartzberg 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.
PubMed 24687833Boeckx 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.
PubMed 28449055Heinemann 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.
PubMed 27592068Modest 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.
PubMed 30614531Peeters 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.
PubMed 29531837Taieb 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.
PubMed 31515083Taieb 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.
PubMed 29080924Boeckx 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.
PubMed 29627309Peeters 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.
PubMed 30013091Sartore-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.
PubMed 34172397Peeters 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.
PubMed 26049686
Study at a glance
From the registry record, last updated by the sponsor on 6 Dec 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00819780
- Acronym / sponsor ID
- 20070509
- Keywords
- Colon Cancer, Colorectal Cancer, Rectal Cancer, Panitumumab, Vectibix, modified FOLFOX 6, mFOLFOX 6, FOLFOX
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 285 participants (actual)
- Lead sponsor
- AmgenIndustry (pharma, biotech, devices)
- Study start
- 24 Apr 2009 (actual)
- Primary completion
- 30 May 2012 (actual)
- Study completion
- 7 Jul 2016 (actual)
- First posted
- 9 Jan 2009 (estimated)
- Results
- Posted 6 Aug 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Panitumumab Plus mFOLFOX6 | Experimental | Drug: Panitumumab, Drug: mFOLFOX6Participants 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. |
| Bevacizumab Plus mFOLFOX6 | Active comparator | Drug: Bevacizumab, Drug: mFOLFOX6Participants 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (10 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PanitumumabAlso: VectibixPanitumumab is a fully human immunoglobulin G (IgG)2 monoclonal antibody antagonist directed against human Epidermal Growth Factor receptor (EGFr). | Drug | Panitumumab Plus mFOLFOX6 |
| BevacizumabAlso: AvastinBevacizumab is a humanized monoclonal IgG1 antibody that is directed against Vascular Endothelial Growth Factor (VEGF). | Drug | Bevacizumab Plus mFOLFOX6 |
| mFOLFOX6mFOLFOX6 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. | Drug | Bevacizumab Plus mFOLFOX6, Panitumumab Plus mFOLFOX6 |
Primary outcome
Progression-free Survival (PFS)
Time frame: From randomization until the data cutoff date of 30 May 2012; median follow-up time was 60 weeks.
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.
13 secondary outcomes
Overall Survival
Time frame: 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
Time frame: From randomization until the data cutoff date of 30 May 2012; median follow-up time was 60 weeks.
Duration of Response
Time frame: From randomization until the data cutoff date of 30 May 2012; median follow-up time was 60 weeks.
Time to Disease Progression
Time frame: From randomization until the data cutoff date of 30 May 2012; median follow-up time was 60 weeks.
Time to Initial Objective Response
Time frame: From randomization until the data cutoff date of 30 May 2012; median follow-up time was 60 weeks.
Resection Rate
Time frame: From randomization until the data cutoff date of 30 May 2012; median follow-up time was 60 weeks.
Progression-free Survival (PFS) in Participants With Wild-type Rat Sarcoma Viral Oncogene Homolog (RAS)
Time frame: From randomization until the data cutoff date of 30 May 2012; median follow-up time was 60 weeks.
Progression-free Survival (PFS) in Participants With Wild-type RAS / V-raf Murine Sarcoma Viral Oncogene Homolog B1 (BRAF)
Time frame: From randomization until the data cutoff date of 30 May 2012; median follow-up time was 60 weeks.
Overall Survival in Participants With Wild-type RAS
Time frame: From randomization until the data cutoff date of 30 May 2012; median follow-up time was 60 weeks.
Overall Survival in Participants With Wild-type RAS / BRAF
Time frame: 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 for Participants With Wild-type RAS
Time frame: 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 for Participants With Wild-type RAS / BRAF
Time frame: From randomization until the data cutoff date of 30 May 2012; median follow-up time was 60 weeks.
Number of Participants With Adverse Events (AEs)
Time frame: 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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Dec 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 28424871Rivera 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.
- Background: PubMed 24687833Schwartzberg 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.
- Background: PubMed 28449055Boeckx 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.
- Background: PubMed 27592068Heinemann 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.
- Background: PubMed 30614531Modest 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.
- Background: PubMed 29531837Peeters 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.
- Background: PubMed 31515083Taieb 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.
- Background: PubMed 29080924Taieb 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.
- Background: PubMed 29627309Boeckx 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.
- Background: PubMed 30013091Peeters 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.
- Background: PubMed 34172397Sartore-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.
- Derived from this study: PubMed 26049686Peeters 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.
- AmgenTrials clinical trials websiteLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
MD study director
Amgen
95 sites in 6 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Panitumumab, Bevacizumab and mFOLFOX6 in people with Colon Cancer and Colorectal Cancer, run by Amgen at 95 sites in 6 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 Dec 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 95 sites in United States, Canada, Germany, Italy, Spain and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 6 Aug 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression-free Survival (PFS) (time frame: From randomization until the data cutoff date of 30 May 2012; median follow-up time was 60 weeks.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00819780, which also lists 12 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Dec 2022.