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NCT00339183

Comparison of Treatment Effect of Chemotherapy With Panitumumab to Chemotherapy Alone

Completed Phase 3 Results posted Last updated 23 September 2022
What this trial tests

Phase 3 trial testing Panitumumab in Metastatic Colorectal Cancer in 1,186 participants. Completed in 1 November 2010.

Timeline
30 June 2006
Primary endpoint
1 April 2009
1 November 2010

Quick facts

Lead sponsorAmgen
PhasePhase 3
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingnone
Primary purposetreatment
Enrollment1,186
Start date30 June 2006
Primary completion1 April 2009
Estimated completion1 November 2010

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.

Progression-free Survival (PFS) Primary · 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.

GroupValue95% CI
Wild-type KRAS - Panitumumab Plus FOLFIRI5.95.5 – 6.7
Wild-type KRAS - FOLFIRI Alone3.93.7 – 5.3
Mutant KRAS - Panitumumab Plus FOLFIRI5.03.8 – 5.6
Mutant KRAS - FOLFIRI Alone4.93.6 – 5.6
Overall Survival Primary · 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.

GroupValue95% CI
Wild-type KRAS - Panitumumab Plus FOLFIRI14.513.0 – 16.0
Wild-type KRAS - FOLFIRI Alone12.511.2 – 14.2
Mutant KRAS - Panitumumab Plus FOLFIRI11.810.4 – 13.3
Mutant KRAS - FOLFIRI Alone11.110.3 – 12.4
Percentage of Participants With an Objective Response Secondary · 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 progressi

GroupValue95% CI
Wild-type KRAS - Panitumumab Plus FOLFIRI35.3529.92 – 41.08
Wild-type KRAS - FOLFIRI Alone9.826.63 – 13.89
Mutant KRAS - Panitumumab Plus FOLFIRI13.369.26 – 18.43
Mutant KRAS - FOLFIRI Alone13.929.78 – 19.00
Time to Disease Progression Secondary · 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.

GroupValue95% CI
Wild-type KRAS - Panitumumab Plus FOLFIRI7.35.9 – 7.5
Wild-type KRAS - FOLFIRI Alone5.33.9 – 5.7
Mutant KRAS - Panitumumab Plus FOLFIRI5.54.5 – 5.7
Mutant KRAS - FOLFIRI Alone5.54.2 – 5.7
Duration of Response Secondary · 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.

GroupValue95% CI
Wild-type KRAS - Panitumumab Plus FOLFIRI7.66.7 – 9.4
Wild-type KRAS - FOLFIRI Alone6.65.7 – 10.4
Mutant KRAS - Panitumumab Plus FOLFIRI6.05.4 – 7.4
Mutant KRAS - FOLFIRI Alone7.44.0 – 8.1
Number of Participants With Adverse Events (AEs) Secondary · 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?"

Any adverse event
GroupValue95% CI
Panitumumab Plus FOLFIRI584
FOLFIRI Alone573
Serious adverse event
GroupValue95% CI
Panitumumab Plus FOLFIRI232
FOLFIRI Alone175
Leading to discontinuation of any study drug
GroupValue95% CI
Panitumumab Plus FOLFIRI123
FOLFIRI Alone64
Treatment-related adverse event (TRAE)
GroupValue95% CI
Panitumumab Plus FOLFIRI577
FOLFIRI Alone542
Serious treatment-related adverse event
GroupValue95% CI
Panitumumab Plus FOLFIRI124
FOLFIRI Alone90
TRAE leading to discontinuation of any study drug
GroupValue95% CI
Panitumumab Plus FOLFIRI97
FOLFIRI Alone34

Adverse events — posted to ClinicalTrials.gov

Time frame: The median treatment period was approximately 6.2 months in the Panitumumab plus FOLFIRI arm, and 4.7 months in the FOLFIRI Alone arm.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Panitumumab Plus FOLFIRI
Serious: 232/587 (40%)
Deaths:
FOLFIRI Alone
Serious: 175/594 (29%)
Deaths:

Serious adverse events (287 terms)

ReactionSystemPanitumumab Plus FOLFIRIFOLFIRI Alone
DiarrhoeaGastrointestinal disorders
PyrexiaGeneral disorders
DehydrationMetabolism and nutrition disorders
VomitingGastrointestinal disorders
Pulmonary embolismRespiratory, thoracic and mediastinal disorders
Febrile neutropeniaBlood and lymphatic system disorders
Abdominal painGastrointestinal disorders
NeutropeniaBlood and lymphatic system disorders
NauseaGastrointestinal disorders
Colorectal cancer metastaticNeoplasms benign, malignant and unspecified (incl cysts and polyps)
Intestinal obstructionGastrointestinal disorders
AstheniaGeneral disorders
General physical health deteriorationGeneral disorders
PainGeneral disorders
Catheter related infectionInfections and infestations
Deep vein thrombosisVascular disorders
Small intestinal obstructionGastrointestinal disorders
CellulitisInfections and infestations
HypokalaemiaMetabolism and nutrition disorders
Back painMusculoskeletal and connective tissue disorders
AnaemiaBlood and lymphatic system disorders
FatigueGeneral disorders
Urinary tract infectionInfections and infestations
RashSkin and subcutaneous tissue disorders
LeukopeniaBlood and lymphatic system disorders
Other adverse events (43 terms — click to expand)

ReactionSystemPanitumumab Plus FOLFIRIFOLFIRI Alone
DiarrhoeaGastrointestinal disorders
RashSkin and subcutaneous tissue disorders
NauseaGastrointestinal disorders
NeutropeniaBlood and lymphatic system disorders
FatigueGeneral disorders
VomitingGastrointestinal disorders
AnorexiaMetabolism and nutrition disorders
Dermatitis acneiformSkin and subcutaneous tissue disorders
ConstipationGastrointestinal disorders
AlopeciaSkin and subcutaneous tissue disorders
StomatitisGastrointestinal disorders
Dry skinSkin and subcutaneous tissue disorders
Abdominal painGastrointestinal disorders
Mucosal inflammationGeneral disorders
HypomagnesaemiaMetabolism and nutrition disorders
AnaemiaBlood and lymphatic system disorders
PruritusSkin and subcutaneous tissue disorders
PyrexiaGeneral disorders
ParonychiaInfections and infestations
Skin fissuresSkin and subcutaneous tissue disorders
ErythemaSkin and subcutaneous tissue disorders
ConjunctivitisEye disorders
AstheniaGeneral disorders
AcneSkin and subcutaneous tissue disorders
HypokalaemiaMetabolism and nutrition disorders
LeukopeniaBlood and lymphatic system disorders
Back painMusculoskeletal and connective tissue disorders
Weight decreasedInvestigations
Oedema peripheralGeneral disorders
CoughRespiratory, thoracic and mediastinal disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
Palmar-plantar erythrodysaesthesia syndromeSkin and subcutaneous tissue disorders
InsomniaPsychiatric disorders
EpistaxisRespiratory, thoracic and mediastinal disorders
PainGeneral disorders
Nail disorderSkin and subcutaneous tissue disorders
DyspepsiaGastrointestinal disorders
HeadacheNervous system disorders
ThrombocytopeniaBlood and lymphatic system disorders
Abdominal pain upperGastrointestinal disorders

Most-reported serious reactions: Diarrhoea, Pyrexia, Dehydration, Vomiting, Pulmonary embolism, Febrile neutropenia, Abdominal pain, Neutropenia.

Data from ClinicalTrials.gov NCT00339183 adverse events section.

Sponsor's own description

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.

Publications & conference data

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

  1. Prognostic and predictive value of primary tumour side in patients with RAS wild-type metastatic colorectal cancer treated with chemotherapy and EGFR directed antibodies in six randomized trials.
    Arnold D, Lueza B, Douillard JY, Peeters M, et al · · 2017 · cited 575× · PMID 28407110 · DOI 10.1093/annonc/mdx175
  2. Emerging strategies to target RAS signaling in human cancer therapy.
    Chen K, Zhang Y, Qian L, Wang P. · · 2021 · cited 164× · PMID 34301278 · DOI 10.1186/s13045-021-01127-w
  3. Health-related quality of life in patients with metastatic colorectal cancer treated with panitumumab in first- or second-line treatment.
    Bennett L, Zhao Z, Barber B, Zhou X, et al · · 2011 · cited 47× · PMID 21989186 · DOI 10.1038/bjc.2011.409
  4. Characteristics and follow-up of postmarketing studies of conditionally authorized medicines in the EU.
    Hoekman J, Klamer TT, Mantel-Teeuwisse AK, Leufkens HG, et al · · 2016 · cited 42× · PMID 26992001 · DOI 10.1111/bcp.12940
  5. 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.
    Boeckx N, Koukakis R, Op de Beeck K, Rolfo C, et al · · 2018 · cited 35× · PMID 29627309 · DOI 10.1016/j.clcc.2018.03.005
  6. Spatiotemporal Heterogeneity across Metastases and Organ-Specific Response Informs Drug Efficacy and Patient Survival in Colorectal Cancer.
    Zhou J, Li Q, Cao Y. · · 2021 · cited 27× · PMID 33589516 · DOI 10.1158/0008-5472.can-20-3665
  7. From Crypts to Cancer: A Holistic Perspective on Colorectal Carcinogenesis and Therapeutic Strategies.
    Gharib E, Robichaud GA. · · 2024 · cited 23× · PMID 39273409 · DOI 10.3390/ijms25179463
  8. 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

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