Clinical trial NCT00339183: Comparison of Treatment Effect of Chemotherapy With Panitumumab to Chemotherapy Alone
Official title: A Randomized, Multicenter Phase 3 Study to Compare the Efficacy of Panitumumab in Combination With Chemotherapy to the Efficacy of Chemotherapy Alone in Patients With Previously Treated Metastatic Colorectal Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Metastatic Colorectal Cancer
Keywords: Oncology
Cancer
Metastatic Colorectal Cancer
EGFr
Panitumumab
Clinical Trial
Amgen
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2006-06-20
Enrollment: 1186
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 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.


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

Primary outcomes:
measure: Progression-free Survival (PFS)
timeFrame: From randomization until the data cut-off date of 8 April 2008. Maximum follow-up time was 17 months.
measure: Overall Survival
timeFrame: From randomization until the data cut-off date of 30 April 2009. Maximum follow-up time was 33 months
Secondary outcomes:
measure: Percentage of Participants With an Objective Response
timeFrame: 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.
measure: Time to Disease Progression
timeFrame: From randomization until the data cut-off date of 30 April 2009. Maximum follow-up time was 33 months
measure: Duration of Response
timeFrame: From randomization until the data cut-off date of 30 April 2009. Maximum follow-up time was 33 months
measure: Number of Participants With Adverse Events (AEs)
timeFrame: From randomization until the data cut-off date of 30 April 2009. Maximum follow-up time was 33 months.
Other outcomes:
Locations:
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
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.
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.
citation: Author and team decided to wait for CALGB RAS data presented Sept 29 at ESMO.
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: 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.
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, 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.
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.
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.