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NCT00508404

Panitumumab Plus FOLFIRI in First-line Treatment of Metastatic Colorectal Cancer

Completed Phase 2 Results posted Last updated 19 November 2019
What this trial tests

Phase 2 trial testing Panitumumab in Metastatic Colorectal Cancer in 154 participants. Completed in 12 June 2012.

Timeline
9 May 2007
Primary endpoint
1 June 2009
12 June 2012

Quick facts

Lead sponsorAmgen
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationna
Designsingle group
Maskingnone
Primary purposetreatment
Enrollment154
Start date9 May 2007
Primary completion1 June 2009
Estimated completion12 June 2012

Drugs / interventions tested

Conditions studied

Sponsor

Amgen — full company profile →

Who can join

18 and older, any sex, with Metastatic Colorectal Cancer. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Objective Response Rate Primary · Tumor response was assessed at Week 8 and every 8 weeks to Week 48 and 3 monthly thereafter until disease progression; median follow-up time was 34 weeks

Objective response rate is defined as the percentage of participants with a best response of complete response or partial response. Disease assessments are based on investigator review of scans using modified Response Evaluation Criteria in Solid Tumors (RECIST) V1.0 criteria. A complete or partial response was confirmed no less than 4-weeks after the criteria for response were first met. Participants with no post-baseline assessment were considered non-responders. Complete Response (CR): disappearance of all target and non-target lesions and no new lesions. Partial Response (PR): At least a

GroupValue95% CI
Wild-type KRAS56.4745.28 – 67.20
Mutant KRAS37.9325.51 – 51.63
Objective Response by 17 Weeks Secondary · Up to Week 17

The percentage of participants with a best response of complete response or partial response by Week 17. Disease assessments are based on investigator review of scans using modified RECIST V1.0 criteria. A complete or partial response was confirmed no less than 4-weeks after the criteria for response were first met. Participants with no post-baseline assessment were considered non-responders.

GroupValue95% CI
Wild-type KRAS49.4138.39 – 60.48
Mutant KRAS34.4822.49 – 48.12
Disease Control Rate Secondary · Tumor response was assessed at Week 8 and every 8 weeks to Week 48 and 3 monthly thereafter until disease progression; median follow-up time was 34 weeks

The percentage of participants whose best response was either a complete or partial response or stable disease, based on modified RECIST v1.0 criteria as assessed by the Investigator. Stable diease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD of target lesions and no progression of existing non-target lesions and no new lesions, or, the persistence of 1 or more non-target lesions not qualifying for either CR or PD if no target lesions were identified at Baseline.

GroupValue95% CI
Wild-type KRAS90.5982.29 – 95.85
Mutant KRAS89.6678.83 – 96.11
Duration of Response Secondary · Tumor response was assessed at Week 8 and every 8 weeks to Week 48 and 3 monthly thereafter until disease progression; median follow-up time was 34 weeks.

Duration of response was calculated only for those participants who had a confirmed complete or partial response, and is defined as the time from first confirmed response to first observed progression. For participants who responded and did not progress by the analysis data cut-off date, duration of response was censored at their last evaluable disease assessment date. Duration of response was analyzed using the Kaplan-Meier method.

GroupValue95% CI
Wild-type KRAS13.09.3 – 13.0
Mutant KRAS7.45.4 – 8.8
Time to Initial Objective Response Secondary · Tumor response was assessed at Week 8 and every 8 weeks to Week 48 and 3 monthly thereafter until disease progression; median follow-up time was 34 weeks.

Time to response is the time from the date of enrollment to the date of first confirmed complete or partial response. Participants with a best response of stable disease at the analysis data cut-off date were censored at their last assessment of SD and participants with all other categories of best response were censored at the maximum observed time to a first confirmed response among all responders. Time to initial objective response was analyzed using Kaplan-Meier methods.

GroupValue95% CI
Wild-type KRAS3.83.4 – NA
Mutant KRASNA5.5 – NA
Progression-free Survival Secondary · From enrollment until the data cut-off date of 18 June 2009; median follow-up time was 34 weeks.

Progression-free survival is the time from the date of enrollment to the date of first observed progression or death, whichever comes first. Participants who were alive and did not progress by the analysis data cut-off date were censored at the last evaluable disease assessment date. Progression-free survival was analyzed using Kaplan-Meier methods.

GroupValue95% CI
Wild-type KRAS8.97.6 – 14.3
Mutant KRAS7.25.6 – 7.8
Time to Disease Progression Secondary · From enrollment until the data cut-off date of 18 June 2009; median follow-up time was 34 weeks.

Time to progression is the time from the enrollment date to the date of first observed progression. For participants who had not progressed by the analysis data cutoff date, time to progressive disease was censored at their last evaluable disease assessment date. Time to disease progression was analyzed using Kaplan-Meier methods.

GroupValue95% CI
Wild-type KRAS11.27.6 – 14.8
Mutant KRAS7.35.7 – 8.9
Duration of Stable Disease Secondary · Tumor response was assessed at Week 8 and every 8 weeks to Week 48 and 3 monthly thereafter until disease progression; median follow-up time was 34 weeks.

Duration of stable disease was calculated only for participants with a best response of stable disease and is defined as the time from enrollment to first observed PD. For participants who did not progress by the analysis data cut-off date, duration of SD was censored at their last evaluable disease assessment date. Duration of stable disease was estimated using Kaplan-Meier methods.

GroupValue95% CI
Wild-type KRAS5.95.8 – 7.6
Mutant KRAS6.14.8 – 7.4
Time to Treatment Failure Secondary · From enrollment until the data cut-off date of 18 June 2009; median follow-up time was 34 weeks.

Time to treatment failure is defined as the time from enrollment to the date the decision was made to end the treatment phase for any reason. For participants who remained in the treatment phase at the analysis data cut-off date, time to treatment failure was censored at the date of their last on-study assessment. Time to treatment failure was analyzed using Kaplan-Meier methods.

GroupValue95% CI
Wild-type KRAS6.96.2 – 7.6
Mutant KRAS5.85.3 – 6.8
Time to Disease Relapse Following Surgical Intervention Secondary · From enrollment until the data cut-off date of 18 June 2009; median follow-up time was 34 weeks.

Calculated only for those participants who underwent surgical intervention, and defined as the time from the date of first post-intervention radiographic disease assessment to the date of first observed PD. Participants with no post-intervention disease assessment had their time to relapse set to zero and censored in the analysis. Participants that had evidence of progression / recurrence at their first post-intervention disease assessment had a time to relapse of zero. For participants who had not progressed by the analysis data cut-off date, time to relapse was censored at the date of their

GroupValue95% CI
Wild-type KRASNANA – NA
Mutant KRASNANA – NA
Resection Rate Secondary · From enrollment until the data cut-off date of 18 June 2009; median follow-up time was 34 weeks.

The percentage of participants who underwent a surgical procedure that resulted in partial reduction or complete eradication of all metastatic disease.

GroupValue95% CI
Wild-type KRAS15.128.30 – 24.46
Mutant KRAS6.781.88 – 16.46

Adverse events — posted to ClinicalTrials.gov

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 6.6 months.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Panitumumab Plus FOLFIRI
Serious: 84/154 (55%)
Deaths:

Serious adverse events (101 terms)

ReactionSystemPanitumumab Plus FOLFIRI
DIARRHOEAGastrointestinal disorders
PULMONARY EMBOLISMRespiratory, thoracic and mediastinal disorders
NEUTROPENIABlood and lymphatic system disorders
VOMITINGGastrointestinal disorders
FATIGUEGeneral disorders
PYREXIAGeneral disorders
DEHYDRATIONMetabolism and nutrition disorders
ABDOMINAL PAINGastrointestinal disorders
CATHETER RELATED COMPLICATIONGeneral disorders
CHEST PAINGeneral disorders
CATHETER RELATED INFECTIONInfections and infestations
PNEUMONIAInfections and infestations
DEEP VEIN THROMBOSISVascular disorders
ILEUSGastrointestinal disorders
INTESTINAL OBSTRUCTIONGastrointestinal disorders
GENERAL PHYSICAL HEALTH DETERIORATIONGeneral disorders
URINARY TRACT INFECTIONInfections and infestations
THROMBOSISVascular disorders
ANAEMIABlood and lymphatic system disorders
ILEUS PARALYTICGastrointestinal disorders
MELAENAGastrointestinal disorders
NAUSEAGastrointestinal disorders
RECTAL HAEMORRHAGEGastrointestinal disorders
STOMATITISGastrointestinal disorders
SUBILEUSGastrointestinal disorders
Other adverse events (55 terms — click to expand)

ReactionSystemPanitumumab Plus FOLFIRI
DIARRHOEAGastrointestinal disorders
NAUSEAGastrointestinal disorders
RASHSkin and subcutaneous tissue disorders
DRY SKINSkin and subcutaneous tissue disorders
ACNESkin and subcutaneous tissue disorders
ALOPECIASkin and subcutaneous tissue disorders
NEUTROPENIABlood and lymphatic system disorders
FATIGUEGeneral disorders
CONSTIPATIONGastrointestinal disorders
ASTHENIAGeneral disorders
VOMITINGGastrointestinal disorders
MUCOSAL INFLAMMATIONGeneral disorders
STOMATITISGastrointestinal disorders
PARONYCHIAInfections and infestations
HYPOKALAEMIAMetabolism and nutrition disorders
ANOREXIAMetabolism and nutrition disorders
CONJUNCTIVITISEye disorders
DERMATITIS ACNEIFORMSkin and subcutaneous tissue disorders
ABDOMINAL PAINGastrointestinal disorders
SKIN FISSURESSkin and subcutaneous tissue disorders
PRURITUSSkin and subcutaneous tissue disorders
HYPOMAGNESAEMIAMetabolism and nutrition disorders
PALMAR-PLANTAR ERYTHRODYSAESTHESIA SYNDROMESkin and subcutaneous tissue disorders
WEIGHT DECREASEDInvestigations
PYREXIAGeneral disorders
ANAEMIABlood and lymphatic system disorders
DYSPEPSIAGastrointestinal disorders
OEDEMA PERIPHERALGeneral disorders
EPISTAXISRespiratory, thoracic and mediastinal disorders
SKIN TOXICITYSkin and subcutaneous tissue disorders
DYSPNOEARespiratory, thoracic and mediastinal disorders
ERYTHEMASkin and subcutaneous tissue disorders
DYSGEUSIANervous system disorders
VERTIGOEar and labyrinth disorders
INSOMNIAPsychiatric disorders
COUGHRespiratory, thoracic and mediastinal disorders
NASOPHARYNGITISInfections and infestations
DRY EYEEye disorders
ABDOMINAL PAIN UPPERGastrointestinal disorders
APHTHOUS STOMATITISGastrointestinal disorders

Most-reported serious reactions: DIARRHOEA, PULMONARY EMBOLISM, NEUTROPENIA, VOMITING, FATIGUE, PYREXIA, DEHYDRATION, ABDOMINAL PAIN.

Data from ClinicalTrials.gov NCT00508404 adverse events section.

Sponsor's own description

To estimate the effect of KRAS mutation status (Wild-type versus Mutant) on objective response rate and other measures of efficacy for patients treated with panitumumab in combination with a chemotherapy regimen of irinotecan, 5-fluorouracil, and leucovorin (FOLFIRI) as first-line therapy for metastatic colorectal cancer (mCRC).

Publications & conference data

6 peer-reviewed publications reference this trial (live from Europe PMC):

  1. First-line panitumumab plus irinotecan/5-fluorouracil/leucovorin treatment in patients with metastatic colorectal cancer.
    Köhne CH, Hofheinz R, Mineur L, Letocha H, et al · · 2012 · cited 57× · PMID 21960318 · DOI 10.1007/s00432-011-1061-6
  2. Skin toxicity and quality of life in patients with metastatic colorectal cancer during first-line panitumumab plus FOLFIRI treatment in a single-arm phase II study.
    Thaler J, Karthaus M, Mineur L, Greil R, et al · · 2012 · cited 26× · PMID 23020584 · DOI 10.1186/1471-2407-12-438
  3. The impact of panitumumab treatment on survival and quality of life in patients with <i>RAS</i> wild-type metastatic colorectal cancer.
    Battaglin F, Puccini A, Ahcene Djaballah S, Lenz HJ. · · 2019 · cited 23× · PMID 31388315 · DOI 10.2147/cmar.s186042
  4. Panitumumab in Metastatic Colorectal Cancer: The Importance of Tumour RAS Status.
    Peeters M, Karthaus M, Rivera F, Terwey JH, et al · · 2015 · cited 18× · PMID 25895463 · DOI 10.1007/s40265-015-0386-x
  5. Relationship Between Tumor Response and Tumor-Related Symptoms in RAS Wild-Type Metastatic Colorectal Cancer: Retrospective Analyses From 3 Panitumumab Trials.
    Taieb J, Geissler M, Rivera F, Karthaus M, et al · · 2019 · cited 5× · PMID 31515083 · DOI 10.1016/j.clcc.2019.07.009
  6. Impact of Primary Tumour Location and Early Tumour Shrinkage on Outcomes in Patients with RAS Wild-Type Metastatic Colorectal Cancer Following First-Line FOLFIRI Plus Panitumumab.
    Köhne CH, Karthaus M, Mineur L, Thaler J, et al · · 2019 · cited 3× · PMID 31300973 · DOI 10.1007/s40268-019-0278-8

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