Neoplasms

Digestive System Diseases

All Conditions

Colorectal Neoplasms

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Colonic Diseases

Intestinal Diseases

Rectal Diseases

Micronutrients

All Drugs and Chemicals

Antineoplastic Agents

Leucovorin

Fluorouracil

Irinotecan

Panitumumab

Antineoplastic Agents, Immunological

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.

Participants received standard chemotherapy regimen (FOLFIRI) consisting of 5-FU, leucovorin and irinotecan. Treatment is administered in cycles every two weeks.

Panitumumab was administered by IV infusion on Day 1 of each 14-day cycle, just before administration of FOLFIRI chemotherapy.

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.

FOLFIRI

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.

Comparison of Treatment Effect of Chemotherapy With Panitumumab to Chemotherapy Alone

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

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 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.

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 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.

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.

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?"

Amgen

One participant was randomized to Panitumumab Plus FOLFIRI, but received FOLFIRI Alone and is included in the FOLFIRI Alone group for safety analyses.

The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.

Participants received 6 mg/kg panitumumab IV plus a standard chemotherapy regimen (FOLFIRI) consisting of 5-FU, leucovorin and irinotecan. Treatment was administered in cycles every two weeks.

Panitumumab Plus FOLFIRI

Participants received FOLFIRI chemotherapy regimen administered in cycles every two weeks.

FOLFIRI Alone

Participants were randomized to 6 mg/kg panitumumab intravenous infusion plus a standard chemotherapy regimen (FOLFIRI) consisting of 5-FU, leucovorin and irinotecan. Treatment was administered in cycles every two weeks.

Participants were randomized to receive a standard chemotherapy regimen (FOLFIRI) consisting of 5-FU, leucovorin and irinotecan. Treatment was administered in cycles every two weeks.

Total

Age, Continuous

Sex: Female, Male

White or Caucasian

Black or African American

Hispanic or Latino

Asian

Japanese

Native Hawaiian or Other Pacific Islander

Aborigine

Other

Race/Ethnicity, Customized

Wild-type KRAS

Mutant KRAS

Unevaluable KRAS

KRAS, the human homolog of the Kirsten rat sarcoma-2 virus oncogene

KRAS Status

Prior Oxaliplatin Exposure for mCRC

Prior Bevacizumab Exposure for mCRC

Grade 0 or 1

Grade 2

Grade 0: Fully active, able to carry on all pre-disease performance without restriction; Grade 1: Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature; Grade 2: Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about \> 50% of waking hours; Grade 3: Capable of only limited self care, confined to a bed or chair \> 50% of waking hours; Grade 4: Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair; Grade 5: Dead

Eastern Cooperative Oncology Group (ECOG) Performance Status

Study Director

An overall 5% significance level was used to compare treatments with respect to both overall survival (OS) and PFS. A 4% and 1% level (2-sided) was used to independently test OS and PFS, respectively.

PFS in the Mutant Efficacy Analysis Set was compared at a 1% level conditional upon first demonstrating a significant difference in PFS in the Wild-type KRAS Efficacy Analysis Set.

Participants with wild-type KRAS were randomized to 6 mg/kg panitumumab plus FOLFIRI chemotherapy regimen administered in cycles every two weeks.

Wild-type KRAS - Panitumumab Plus FOLFIRI

Participants with wild-type KRAS were randomized to FOLFIRI chemotherapy regimen administered in cycles every two weeks.

Wild-type KRAS - FOLFIRI Alone

Participants with mutant KRAS were randomized to 6 mg/kg panitumumab plus FOLFIRI chemotherapy regimen administered in cycles every two weeks.

Mutant KRAS - Panitumumab Plus FOLFIRI

Participants with mutant KRAS were randomized to FOLFIRI chemotherapy regimen administered in cycles every two weeks.

Mutant KRAS - FOLFIRI Alone

KRAS Efficacy Analysis Set (participants for whom KRAS status was assessed)

Progression-free Survival (PFS)

The treatment effect on OS in the Mutant KRAS Efficacy Analysis Set was compared at the 4% level conditional on first demonstrating a significant OS treatment effect in the Wild-type KRAS Efficacy Analysis Set.

Overall Survival

KRAS Central Tumor Response Analysis Set: subset of participants with at least one uni-dimensionally measurable lesion per the modified RECIST criteria per blinded central radiology review for whom KRAS was assessed.

Percentage of Participants With an Objective Response

Time to Disease Progression

KRAS Central Tumor Response Analysis Set: Responders

Duration of Response

Any adverse event

Serious adverse event

Leading to discontinuation of any study drug

Treatment-related adverse event (TRAE)

Serious treatment-related adverse event

TRAE leading to discontinuation of any study drug

Safety analysis set: all participants who received at least 1 dose of panitumumab or chemotherapy. One participant was randomized to Panitumumab Plus FOLFIRI, but received FOLFIRI Alone and is included in the FOLFIRI Alone group for safety analyses.

Spots Global Cancer Trial Database for Comparison of Treatment Effect of Chemotherapy With Panitumumab to Chemotherapy Alone

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

Useful links and downloads for this trial