NCT00339183 · CITED IN SOURCE DOCUMENTS

Comparison of Treatment Effect of Chemotherapy With Panitumumab to Chemotherapy Alone

An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.

Phase: PHASE3
Status at capture: COMPLETED
Registry last update: 2022-09-23

The purpose of this study is to evaluate the treatment effect of panitumumab plus FOLFIRI compared to FOLFIRI alone as second line therapy for metastatic colorectal cancer.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

Progression-free Survival (PFS)

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outcome · POSTED

Overall Survival

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outcome · POSTED

Percentage of Participants With an Objective Response

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outcome · POSTED

Time to Disease Progression

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outcome · POSTED

Duration of Response

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outcome · POSTED

Number of Participants With Adverse Events (AEs)

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part

eligibility Criteria: Inclusion Criteria: * Man or woman at least 18 years old * Diagnosis of metastatic colorectal cancer (mCRC) * One and only one chemotherapy regimen for mCRC consisting of first-line 5-FU -based chemotherapy * Radiologically documented disease progression per modified Response Evaluation Criteria in Solid Tumors (RECIST) criteria during treatment or within 6 months of last dose of first-line chemotherapy * At least 1 uni-dimensionally measurable lesion of at least 20 mm per modified RECIST * Eastern Cooperative Oncology Group (ECOG) status of 0, 1, or 2 * Paraffin-embedded tumor tissue from the primary tumor or metastasis available for central analyses * Adequate hematologic, renal, and hepatic functions * Negative pregnancy test within 72 hours of enrollment * Other protocol-specified criteria may apply Exclusion Criteria: * History of or known presence of central nervous system (CNS) metastases * History of another primary cancer within 5 years of randomization * Prior irinotecan therapy * Prior anti-epidermal growth factor receptor (EGFr) antibody therapy or treatment with small molecule EGFr inhibitors * Any investigational agent or therapy within 30 days before randomization * Known allergy or hypersensitivity to irinotecan, 5-FU or leucovorin * History of interstitial lung disease or evidence of interstitial lung disease on baseline chest computed tomography (CT) scan * Active inflammatory bowel disease or other bowel disease causing chronic diarrhea * Known positive tests for human immunodefiency virus (HIV), hepatitis C viris (HCV), acute or chronic active hepatitis B virus (HBV) * Major surgery within 28 days of randomization or minor surgical procedure within 14 days of randomization * Pregnant or breast-feeding * Man or woman of child-bearing potential not consenting to use adequate contraceptive methods or abstinence during the course of the study and for 6 months after last study drug administration (women) or 1 month after last study drug administration (men) * Other protocol-specified criteria may apply
healthy Volunteers: false
minimum Age: 18 Years
sex: ALL
std Ages: ADULT
OLDER_ADULT

Treatment arms and interventions

arm Groups

description
Participants received panitumumab as an intravenous (IV) infusion at a dose of 6 mg/kg plus a standard chemotherapy regimen (FOLFIRI) consisting of 5-fluorouracil (5-FU), leucovorin and irinotecan. Treatment was administered in cycles every two weeks.
intervention Names
Drug: Panitumumab
Drug: FOLFIRI
label
Panitumumab Plus FOLFIRI
type
EXPERIMENTAL
description
Participants received standard chemotherapy regimen (FOLFIRI) consisting of 5-FU, leucovorin and irinotecan. Treatment is administered in cycles every two weeks.
intervention Names
Drug: FOLFIRI
label
FOLFIRI Alone
type
ACTIVE_COMPARATOR

interventions

arm Group Labels
Panitumumab Plus FOLFIRI
description
Panitumumab was administered by IV infusion on Day 1 of each 14-day cycle, just before administration of FOLFIRI chemotherapy.
name
Panitumumab
other Names
Vectibix®
type
DRUG
arm Group Labels
FOLFIRI Alone
Panitumumab Plus FOLFIRI
description
FOLFIRI chemotherapy was initiated on Day 1 of each treatment cycle at the following starting doses: irinotecan 180 mg/m\^2, leucovorin 400 mg/m\^2 racemate (or 200 mg/m\^2 I-leucovorin), 5-FU bolus 400 mg/m\^2, 5-FU infusion 2400 mg/m\^2.
name
FOLFIRI
type
DRUG

Study design

allocation

RANDOMIZED

intervention Model

PARALLEL

masking Info

masking: NONE

primary Purpose

TREATMENT

Enrollment

count: 1186
type: ACTUAL

Registered outcome plans (not posted results)

primary Outcomes

description
Progression-free survival was defined as the time from randomization to first disease progression per modified Response Evaluation Criteria in Solid Tumors (RECIST) criteria or death, based on independent central radiological assessment. Participants who were alive but did not meet criteria for progression by the data cutoff date were censored at their last evaluable disease assessment date. Progressive disease is defined as a ≥ 20% increase in the size of target lesions or unequivocal progression of existing non-target lesions or any new lesions.
measure
Progression-free Survival (PFS)
time Frame
From randomization until the data cut-off date of 8 April 2008. Maximum follow-up time was 17 months.
description
Overall survival was defined as the time from randomization to the date of death. Participants who had not died by the analysis data cutoff date had their time of death censored at their last contact date.
measure
Overall Survival
time Frame
From randomization until the data cut-off date of 30 April 2009. Maximum follow-up time was 33 months

secondary Outcomes

description
Participants were evaluated for tumor response per the modified Response Evaluation Criteria in Solid Tumors (RECIST) criteria every 8 weeks until disease progression. Objective response was defined as the incidence of either a confirmed complete or partial response (CR or PR) while on study, as determined by blinded independent central review and confirmed no less than 4-weeks after the criteria for response are first met. CR: Disappearance of all target and non-target lesions and no new lesions. PR: At least a 30% decrease in the sum of the longest diameter of target lesions and no progression of non-target or no new lesions, or, disappearance of all target lesions and the persistence of ≥ 1 non-target lesion not qualifying for either CR or progressive disease. Participants without a post-baseline assessment were considered non-responders.
measure
Percentage of Participants With an Objective Response
time Frame
Every 8 weeks until disease progression up to the data cut-off date of 30 April 2009. Maximum time on follow-up was 33 months.
description
Time to progression was defined as the time from the randomization date to the date of first observed disease progression per the modified RECIST criteria. Participants not meeting these criteria by the analysis data cutoff date were censored at their last evaluable disease assessment date. Progressive disease is defined as a ≥ 20% increase in the size of target lesions or unequivocal progression of existing non-target lesions or any new lesions.
measure
Time to Disease Progression
time Frame
From randomization until the data cut-off date of 30 April 2009. Maximum follow-up time was 33 months
description
Calculated only for those participants with an objective response as the time from the first objective response (subsequently confirmed within no less than 4 weeks) to first observed disease progression per modified-RECIST criteria. Participants not meeting these criteria by the analysis data cutoff date were censored at their last evaluable disease assessment date. Progressive disease is defined as a ≥ 20% increase in the size of target lesions or unequivocal progression of existing non-target lesions or any new lesions.
measure
Duration of Response
time Frame
From randomization until the data cut-off date of 30 April 2009. Maximum follow-up time was 33 months
description
A serious adverse event (SAE) is defined by regulatory authorities as one that • is fatal • is life threatening (places the subject at immediate risk of death) • requires in-patient hospitalization or prolongation of existing hospitalization • results in persistent or significant disability/incapacity • is a congenital anomaly/birth defect • other significant medical hazard. The relationship of the adverse event to the study treatment was assessed by the Investigator by means of the question: "Is there a reasonable possibility that the event may have been caused by the study treatment?"
measure
Number of Participants With Adverse Events (AEs)
time Frame
From randomization until the data cut-off date of 30 April 2009. Maximum follow-up time was 33 months.

Full study description

brief Summary: The purpose of this study is to evaluate the treatment effect of panitumumab plus FOLFIRI compared to FOLFIRI alone as second line therapy for metastatic colorectal cancer.

Source references

references

citation
Peeters M, Price TJ, Cervantes A, Sobrero AF, Ducreux M, Hotko Y, Andre T, Chan E, Lordick F, Punt CJ, Strickland AH, Wilson G, Ciuleanu TE, Roman L, Van Cutsem E, Tian Y, Sidhu R. Final results from a randomized phase 3 study of FOLFIRI +/- panitumumab for second-line treatment of metastatic colorectal cancer. Ann Oncol. 2014 Jan;25(1):107-16. doi: 10.1093/annonc/mdt523.
pmid
24356622
type
BACKGROUND
citation
Peeters M, Price TJ, Cervantes A, Sobrero AF, Ducreux M, Hotko Y, Andre T, Chan E, Lordick F, Punt CJ, Strickland AH, Wilson G, Ciuleanu TE, Roman L, Van Cutsem E, Tzekova V, Collins S, Oliner KS, Rong A, Gansert J. Randomized phase III study of panitumumab with fluorouracil, leucovorin, and irinotecan (FOLFIRI) compared with FOLFIRI alone as second-line treatment in patients with metastatic colorectal cancer. J Clin Oncol. 2010 Nov 1;28(31):4706-13. doi: 10.1200/JCO.2009.27.6055. Epub 2010 Oct 4.
pmid
20921462
type
BACKGROUND
citation
Author and team decided to wait for CALGB RAS data presented Sept 29 at ESMO.
type
BACKGROUND
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.
pmid
30013091
type
BACKGROUND
citation
Shi Y, Wan X, Tan C, Li J, Peng L. Model-Based Cost-Effectiveness Analysis of Panitumumab Plus FOLFIRI for the Second-Line Treatment of Patients with Wild-Type Ras Metastatic Colorectal Cancer. Adv Ther. 2020 Feb;37(2):847-859. doi: 10.1007/s12325-019-01214-y. Epub 2020 Jan 4.
pmid
31902066
type
DERIVED
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.
pmid
29627309
type
DERIVED
citation
Peeters M, Oliner KS, Price TJ, Cervantes A, Sobrero AF, Ducreux M, Hotko Y, Andre T, Chan E, Lordick F, Punt CJ, Strickland AH, Wilson G, Ciuleanu TE, Roman L, Van Cutsem E, He P, Yu H, Koukakis R, Terwey JH, Jung AS, Sidhu R, Patterson SD. Analysis of KRAS/NRAS Mutations in a Phase III Study of Panitumumab with FOLFIRI Compared with FOLFIRI Alone as Second-line Treatment for Metastatic Colorectal Cancer. Clin Cancer Res. 2015 Dec 15;21(24):5469-79. doi: 10.1158/1078-0432.CCR-15-0526. Epub 2015 Sep 4.
pmid
26341920
type
DERIVED
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.
pmid
26049686
type
DERIVED
citation
Weeraratne D, Chen A, Pennucci JJ, Wu CY, Zhang K, Wright J, Perez-Ruixo JJ, Yang BB, Kaliyaperumal A, Gupta S, Swanson SJ, Chirmule N, Starcevic M. Immunogenicity of panitumumab in combination chemotherapy clinical trials. BMC Clin Pharmacol. 2011 Nov 9;11:17. doi: 10.1186/1472-6904-11-17.
pmid
22070868
type
DERIVED