Comparison of Treatment Effect of Chemotherapy With Panitumumab to Chemotherapy Alone

• ClinicalTrials.gov Identifier: NCT00339183
• Recruitment Status: Completed
• First Posted: June 20, 2006
• Results First Posted: May 6, 2014
• Last Update Posted: September 23, 2022
• Sponsor: Amgen
• Information provided by (Responsible Party): Amgen

Tracking Information

• First Submitted Date: June 16, 2006
• First Posted Date: June 20, 2006
• Results First Submitted Date: April 3, 2014
• Results First Posted Date: May 6, 2014
• Last Update Posted Date: September 23, 2022
• Actual Study Start Date: June 30, 2006
• Actual Primary Completion Date: April 1, 2009 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 3, 2014)

• 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. ]
  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.
• Overall Survival [ Time Frame: From randomization until the data cut-off date of 30 April 2009. Maximum follow-up time was 33 months ]
  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.

• Original Primary Outcome Measures (submitted: June 16, 2006): Efficacy: Overall Survival (OS) and progression-free survival (PFS)

Current Secondary Outcome Measures (submitted: April 3, 2014)

• 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. ]
  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.
• 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 ]
  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.
• Duration of Response [ Time Frame: From randomization until the data cut-off date of 30 April 2009. Maximum follow-up time was 33 months ]
  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.
• 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. ]
  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?"

• Original Secondary Outcome Measures (submitted: June 16, 2006): Efficacy: Overall objective response rate, time to progression, and duration of response. Safety: Incidence of AEs and significant laboratory changes
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Metastatic Colorectal Cancer

Intervention

• Drug: Panitumumab
  Panitumumab was administered by IV infusion on Day 1 of each 14-day cycle, just before administration of FOLFIRI chemotherapy.
  Other Name: Vectibix®
• Drug: FOLFIRI
  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.

Study Arms

• Experimental: Panitumumab Plus FOLFIRI
  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.
  Interventions:

  • Drug: Panitumumab
  • Drug: FOLFIRI
• Active Comparator: FOLFIRI Alone
  Participants received standard chemotherapy regimen (FOLFIRI) consisting of 5-FU, leucovorin and irinotecan. Treatment is administered in cycles every two weeks.
  Intervention: Drug: FOLFIRI

Publications *

• 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. Erratum In: Ann Oncol. 2014 Mar;25(3):757. Ann Oncol. 2014 Mar;25(3):757.
• 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.
• Author and team decided to wait for CALGB RAS data presented Sept 29 at ESMO.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: July 15, 2010): 1186
• Original Enrollment (submitted: June 16, 2006): 1100
• Actual Study Completion Date: November 1, 2010
• Actual Primary Completion Date: April 1, 2009 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Not Provided
• Removed Location Countries: Australia, Austria, Belgium, Bulgaria, Czech Republic, Finland, France, Germany, Ireland, Italy, Japan, Lithuania, Netherlands, Norway, Poland, Portugal, Romania, Russian Federation, Slovakia, Spain, Sweden, Switzerland, Ukraine, United Kingdom, United States

Administrative Information

• NCT Number: NCT00339183
• Other Study ID Numbers: 20050181
• Has Data Monitoring Committee: Not Provided
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Amgen
• Original Responsible Party: Not Provided
• Current Study Sponsor: Amgen
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: MD; Amgen

• PRS Account: Amgen
• Verification Date: September 2022