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

Phase 3
Completed
Conditions
Metastatic Colorectal Cancer
Interventions
Drug: FOLFOX regimen
Registration Number
NCT00364013
Lead Sponsor
Amgen
Brief Summary

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

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
1183
Inclusion Criteria
  • Man or woman at least 18 years old
  • Diagnosis of metastatic colorectal cancer
  • At least 1 uni-dimensionally measurable lesion of at least 20 mm per modified RECIST
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
  • Paraffin-embedded tumor tissue from the primary tumor or metastasis available for central analyse
Exclusion Criteria
  • History or known presence of central nervous system (CNS) metastases
  • History of another primary cancer, except: Curatively treated in situ cervical cancer, or Curatively resected non-melanoma skin cancer, or Other primary solid tumor curatively treated with no known active disease present and no treatment administered for ≥ 5 years before randomization
  • Prior chemotherapy or systemic therapy for the treatment of metastatic colorectal carcinoma except: adjuvant fluoropyrimidine-based chemotherapy or prior fluoropyrimidine therapy administered solely for the purpose of radiosensitization
  • Prior oxaliplatin therapy
  • Prior anti-epidermal growth factor receptor (EGFr) antibody therapy (eg, cetuximab) or treatment with small molecule EGFr inhibitors (eg, erlotinib)
  • Clinically significant cardiovascular disease (including myocardial infarction, unstable angina, symptomatic congestive heart failure, serious uncontrolled cardiac arrhythmia) 1 year prior to randomization History of interstitial lung disease (eg, pneumonitis or pulmonary fibrosis) or evidence of interstitial lung disease on baseline chest computed tomography (CT) scan
  • Active inflammatory bowel disease or other bowel disease causing chronic diarrhea (defined as > Common terminology criteria (CTC) grade 2 [CTCAE version 3.0])
  • Peripheral sensory neuropathy with functional impairment

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
FOLFOX + PanitumumabFOLFOX regimenParticipants received panitumumab, 6 mg/kg on Day 1 and FOLFOX chemotherapy regimen on Days 1 and 2 of each 14-day cycle until disease progression or unacceptable toxicity.
FOLFOXFOLFOX regimenParticipants received FOLFOX chemotherapy regimen on Days 1 and 2 of each 14-day cycle until disease progression or until unacceptable toxicity.
FOLFOX + PanitumumabPanitumumabParticipants received panitumumab, 6 mg/kg on Day 1 and FOLFOX chemotherapy regimen on Days 1 and 2 of each 14-day cycle until disease progression or unacceptable toxicity.
Primary Outcome Measures
NameTimeMethod
Progression-free SurvivalFrom 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.

Secondary Outcome Measures
NameTimeMethod
Overall SurvivalFrom 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.

Percentage of Participants With an Objective ResponseEvery 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 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.

Number of Participants With Adverse Events (AEs)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?"

Duration of ResponseEvery 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.

Time to ProgressionFrom 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.

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