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NCT00364013

PRIME: Panitumumab Randomized Trial In Combination With Chemotherapy for Metastatic Colorectal Cancer to Determine Efficacy

Completed Phase 3 Results posted Last updated 7 November 2022
What this trial tests

Phase 3 trial testing Panitumumab in Metastatic Colorectal Cancer in 1,183 participants. Completed in 22 March 2013.

Timeline
1 August 2006
Primary endpoint
1 August 2009
22 March 2013

Quick facts

Lead sponsorAmgen
PhasePhase 3
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingnone
Primary purposetreatment
Enrollment1,183
Start date1 August 2006
Primary completion1 August 2009
Estimated completion22 March 2013

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 Primary · From randomization until the data cutoff date of 30 September 2008. Maximum follow-up time was 109 weeks.

Progression-free survival (PFS), assessed by central radiological assessment, was defined as the time from randomization to disease progression per modified response evaluation criteria in solid tumors (RECIST) criteria or death. 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 - FOLFOX + Panitumumab9.69.2 – 11.1
Wild-type KRAS - FOLFOX8.07.5 – 9.3
Mutant KRAS - FOLFOX + Panitumumab7.36.3 – 8.0
Mutant KRAS - FOLFOX8.87.7 – 9.4
Overall Survival Secondary · From randomization until the data cutoff date of 28 August 2009. Maximum time on follow-up was 153 weeks.

The definition of overall survival is the time from randomization to death; participants who were alive at the analysis data cutoff were censored at their last contact date.

GroupValue95% CI
Wild-type KRAS - FOLFOX + Panitumumab23.920.3 – 28.3
Wild-type KRAS - FOLFOX19.717.6 – 22.6
Mutant KRAS - FOLFOX + Panitumumab15.513.1 – 17.6
Mutant KRAS - FOLFOX19.316.5 – 21.8
Percentage of Participants With an Objective Response Secondary · Every 8 weeks until disease progression up to the data cut-off date of 30 September 2008; Maximum follow-up time was 109 weeks.

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 by central radiological assessment was defined as the incidence of either a confirmed complete or partial response (CR or PR) while on the first-line treatment, 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 t

GroupValue95% CI
Wild-type KRAS - FOLFOX + Panitumumab55.2149.55 – 60.77
Wild-type KRAS - FOLFOX47.6842.12 – 53.28
Mutant KRAS - FOLFOX + Panitumumab39.5332.95 – 46.41
Mutant KRAS - FOLFOX40.2833.61 – 47.24
Time to Progression Secondary · From randomization until the data cut-off date of 30 September 2008; Maximum follow-up time was 109 weeks.

Time to progression was defined as time from randomization date to date of disease progression per the modified RECIST criteria.

GroupValue95% CI
Wild-type KRAS - FOLFOX + Panitumumab10.89.4 – 12.4
Wild-type KRAS - FOLFOX9.27.7 – 9.9
Mutant KRAS - FOLFOX + Panitumumab7.57.2 – 8.9
Mutant KRAS - FOLFOX9.07.7 – 9.5
Duration of Response Secondary · Every 8 weeks until disease progression up to the data cut-off date of 30 September 2008; Maximum follow-up time was 109 weeks.

Duration of response was calculated only for those participants with a confirmed CR or PR, as the time from the first CR or PR (subsequently confirmed within no less than 4 weeks) to first observed disease progression per modified RECIST criteria, based on a blinded central review.

GroupValue95% CI
Wild-type KRAS - FOLFOX + Panitumumab11.19.5 – 13.0
Wild-type KRAS - FOLFOX8.87.8 – 9.7
Mutant KRAS - FOLFOX + Panitumumab7.45.9 – 8.3
Mutant KRAS - FOLFOX8.06.5 – 9.5
Number of Participants With Adverse Events (AEs) Secondary · From randomization until the data cut-off date of 28 August 2009; Maximum time on follow-up was 153 weeks.

A serious adverse event (SAE) is defined as an AE that • is fatal • is life threatening • 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
FOLFOX + Panitumumab583
FOLFOX Alone579
Serious adverse event
GroupValue95% CI
FOLFOX + Panitumumab262
FOLFOX Alone198
Leading to discontinuation of any study drug
GroupValue95% CI
FOLFOX + Panitumumab136
FOLFOX Alone84
Treatment-related adverse event (TRAE)
GroupValue95% CI
FOLFOX + Panitumumab581
FOLFOX Alone565
Serious treatment-related adverse event
GroupValue95% CI
FOLFOX + Panitumumab162
FOLFOX Alone89
TRAE leading to discontinuation of any study drug
GroupValue95% CI
FOLFOX + Panitumumab117
FOLFOX Alone63

Adverse events — posted to ClinicalTrials.gov

Time frame: The median treatment period was around 7.7 months in the Panitumumab arm, and around 6.7 months in the Chemo alone arm.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Panitumumab Plus FOLFOX
Serious: 262/585 (45%)
Deaths:
FOLFOX Alone
Serious: 198/584 (34%)
Deaths:

Serious adverse events (295 terms)

ReactionSystemPanitumumab Plus FOLFOXFOLFOX Alone
DiarrhoeaGastrointestinal disorders
DehydrationMetabolism and nutrition disorders
Intestinal obstructionGastrointestinal disorders
VomitingGastrointestinal disorders
PyrexiaGeneral disorders
Febrile neutropeniaBlood and lymphatic system disorders
Abdominal painGastrointestinal disorders
Pulmonary embolismRespiratory, thoracic and mediastinal disorders
NauseaGastrointestinal disorders
SepsisInfections and infestations
NeutropeniaBlood and lymphatic system disorders
PneumoniaInfections and infestations
RashSkin and subcutaneous tissue disorders
AnorexiaMetabolism and nutrition disorders
Colorectal cancer metastaticNeoplasms benign, malignant and unspecified (incl cysts and polyps)
Deep vein thrombosisVascular disorders
AnaemiaBlood and lymphatic system disorders
Renal failureRenal and urinary disorders
General physical health deteriorationGeneral disorders
Urinary tract infectionInfections and infestations
IleusGastrointestinal disorders
AstheniaGeneral disorders
Mucosal inflammationGeneral disorders
Catheter related infectionInfections and infestations
HypokalaemiaMetabolism and nutrition disorders
Other adverse events (56 terms — click to expand)

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

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

Data from ClinicalTrials.gov NCT00364013 adverse events section.

Sponsor's own description

The purpose of this study is to determine the treatment effect of panitumumab in combination with FOLFOX compared to FOLFOX alone as first line therapy for metastatic colorectal cancer

Publications & conference data

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

  1. Panitumumab-FOLFOX4 treatment and RAS mutations in colorectal cancer.
    Douillard JY, Oliner KS, Siena S, Tabernero J, et al · · 2013 · cited 1652× · PMID 24024839 · DOI 10.1056/nejmoa1305275
  2. Comprehensive review of targeted therapy for colorectal cancer.
    Xie YH, Chen YX, Fang JY. · · 2020 · cited 1162× · PMID 32296018 · DOI 10.1038/s41392-020-0116-z
  3. 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
  4. Understanding the role of primary tumour localisation in colorectal cancer treatment and outcomes.
    Stintzing S, Tejpar S, Gibbs P, Thiebach L, et al · · 2017 · cited 200× · PMID 28787661 · DOI 10.1016/j.ejca.2017.07.016
  5. Primary tumor sidedness has an impact on prognosis and treatment outcome in metastatic colorectal cancer: results from two randomized first-line panitumumab studies.
    Boeckx N, Koukakis R, Op de Beeck K, Rolfo C, et al · · 2017 · cited 165× · PMID 28449055 · DOI 10.1093/annonc/mdx119
  6. 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
  7. Clinical development of targeted and immune based anti-cancer therapies.
    Seebacher NA, Stacy AE, Porter GM, Merlot AM. · · 2019 · cited 147× · PMID 30975211 · DOI 10.1186/s13046-019-1094-2
  8. The Role of the Tumor Microenvironment and Treatment Strategies in Colorectal Cancer.
    Chen Y, Zheng X, Wu C. · · 2021 · cited 77× · PMID 34925375 · DOI 10.3389/fimmu.2021.792691

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