Neoplasms

Digestive System Diseases

All Conditions

Colorectal Neoplasms

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Colonic Diseases

Intestinal Diseases

Rectal Diseases

Analgesics

All Drugs and Chemicals

Anti-Infective Agents

Antineoplastic Agents

Anti-Bacterial Agents

Antibiotics, Antitubercular

Mitogens

Panitumumab

Antineoplastic Agents, Immunological

Participants received panitumumab administered intravenously 6 mg/kg every 14 days plus BSC until disease progression, withdrawal of consent, death, or intolerance of study drug.

Participants received best supportive care until disease progression, withdrawal of consent, or death.

BSC was defined as the best palliative care available as judged appropriate by the investigator and according to institutional guidelines and could include antibiotics, analgesics, radiation therapy for pain control (limited to bone metastases), corticosteroids, transfusions, psychotherapy, growth factors, palliative surgery, or any other symptomatic therapy as clinically indicated.

Best Supportive Care (BSC)

The purpose of this study is to evaluate the benefit of panitumumab in addition to best supportive care compared to best supportive care alone in patients with chemorefractory wild-type KRAS (Kirsten rat sarcoma viral oncogene homolog) metastatic colorectal cancer.

Comparison of Survival Benefit of Panitumumab With Supportive Care to Best Supportive Care Alone in Patients With Metastatic Colorectal Cancer

A Phase 3, Multicenter, Randomized, Open-label Trial to Evaluate the Survival Benefit of Panitumumab and Best Supportive Care, Compared to Best Supportive Care Alone, in Subjects With Chemorefractory Wild-type KRAS Metastatic Colorectal Cancer

Overall survival was defined as the time from the randomization date to the date of death. Participants who had not died by the analysis data cut-off date were censored at their last contact date and participants with survival data obtained after the planned analysis data cut-off date had survival censored at the cut-off date.

Progression-free survival (PFS) was defined as the time from the randomization date to the date of disease progression per Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1 or death. Progressive disease (PD): At least a 20% increase in the size of target lesions compared with the smallest size since treatment started and an absolute increase of at least 5 mm, any new lesions or an increase in size of non-target lesions thought be ≥ 20% and an absolute increase of at least 5 mm, or significant increase in pleural effusions, ascites or other fluid collections with cytologic proof of malignancy. Participants who were alive and did not meet the criteria for progression by the analysis data cut-off date were censored at their last evaluable disease assessment date.

A secondary efficacy endpoint was overall survival in participants with wild-type rat sarcoma viral oncogene homolog (RAS) (without mutation in exons 2 \[codons 12 and 13\], 3 \[codons 59 and 61\], and 4 \[codons 117 and 146\] of KRAS and neuroblastoma RAS viral oncogene (NRAS)). In participants with wild-type RAS, RAS mutation status was defined by KRAS exon 2 mutation status per clinical trial assay testing and mutation status of KRAS exon 3 and 4 and NRAS exons 2, 3 and 4 per Sanger bi-directional sequencing. Overall survival was defined as the time from the randomization date to the date of death. Participants who had not died by the analysis data cut-off date were censored at their last contact date and participants with survival data obtained after the planned analysis data cut-off date had survival censored at the cut-off date.

PFS was defined as the time from the randomization date to the date of disease progression per RECIST version 1.1 or death.

Progressive disease (PD): At least a 20% increase in the size of target lesions compared with the smallest size since treatment started and an absolute increase of at least 5 mm, any new lesions, or an increase in size of non-target lesions thought be ≥ 20% with an absolute increase of at least 5 mm, or significant increase in pleural effusions, ascites or other fluid collections with cytologic proof of malignancy. Participants who were alive and did not meet the criteria for progression by the analysis data cut-off date were censored at their last evaluable disease assessment date.

Objective response rate (ORR) is defined as the percentage of participants with either a complete response (CR) or partial response (PR) per RECIST version 1.1. Radiographic tumor assessments and investigator's assessment of response were performed at Week 4, Week 8, and then every 8 weeks until disease progression (radiographic or clinical progression). CR: Disappearance of all target and non-target lesions and no new lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm. PR: At least a 30% decrease in the size of target lesions with no progression of non-target lesions and no new lesions, or, the disappearance of all target lesions with persistence of one or more non-target lesions not qualifying for either CR or PD and no new lesions.

Objective response rate is defined as the percentage of participants with either a complete response (CR) or partial response (PR) per RECIST version 1.1. Radiographic tumor assessments and investigator's assessment of response were performed at Week 4, Week 8, and then every 8 weeks until disease progression (radiographic or clinical progression). CR: Disappearance of all target and non-target lesions and no new lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm. PR: At least a 30% decrease in the size of target lesions with no progression of non-target lesions and no new lesions, or, the disappearance of all target lesions with persistence of one or more non-target lesions not qualifying for either CR or PD and no new lesions.

The severity of each AE was graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 (Grade 1 = Mild; 2 = Moderate (discomfort enough to cause interference with usual activity); 3 = Severe (incapacitating with inability to work or do usual activity); 4 = Life-threatening and 5 = Fatal), with the exception of the skin-or nail-related AEs which were graded using a CTCAE version 3.0 with modifications. A serious AE was defined as an AE that met at least 1 of the following criteria: • fatal, • life-threatening, • required in-patient hospitalization or prolongation of existing hospitalization, • resulted in persistent or significant disability/incapacity, • congenital anomaly/birth defect, and/or • other medically important serious event. Treatment-related AEs (TRAEs) are those the investigator considered there was reasonable possibility that the event might have been caused by study drug.

QT interval is a measure of the time between the start of the Q wave and the end of the T wave in the heart's electrical cycle as measured by electrocardiogram (ECG). QTc is the QT interval corrected for heart rate. To evaluate the effect of panitumumab treatment on the QTc interval length among participants treated with panitumumab, ECGs were collected at the following time points from participants randomized to panitumumab arm at a limited number of sites: Week 1 prior to the first panitumumab infusion (Baseline) and within 30 minutes following the end of the first infusion of panitumumab (Cmax), Week 7 after 3 doses of panitumumab (steady state), and at the safety follow-up visit. The ECGs were submitted for independent central review to calculate the reported QTc interval. QTc was calculated using both the Bazett correction (QTcB) and the Fridericia correction (QTcF).

Amgen

Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.

Panitumumab Plus BSC

BSC Alone

Participants received panitumumab administered intravenously 6 mg/kg every 14 days plus best supportive care (BSC) until disease progression, withdrawal of consent, death, or intolerance of study drug.

Panitumumab + BSC

Total

Age, Continuous

Sex: Female, Male

Hispanic or Latino

Not Hispanic or Latino

Race/Ethnicity, Customized

American Indian or Alaska Native

Asian

White

Other

Europe

Asia

Rest of world

Geographic Region

Grade 0

Grade 1

Grade 2

A scale to assess a patient's disease status. 0 = Fully active, able to carry out all pre-disease performance without restriction; 1 = Restricted in physically strenuous activity, ambulatory and able to carry out work of a light nature; 2 = Ambulatory and capable of all self care, unable to carry out any work activities. Up and about \> 50% of waking hours; 3 = Capable of only limited self-care, confined to bed or chair \> 50% of waking hours; 4 = Completely disabled, confined to bed or chair; 5 = Dead.

Eastern Cooperative Oncology Group (ECOG) Performance Status

Colon

Rectum

Missing

Location of Primary Tumor

Study Director

The primary hypothesis was that panitumumab plus BSC would improve overall survival compared to BSC alone. A comparison between treatments was performed using the log-rank test stratified by the randomization factors at a 5% significance level.

Intent to Treat (ITT) Analysis Set (all randomized participants); participants in the ITT Analysis Set were required to have wild-type KRAS exon 2 (codons 12 and 13, alleles G12A, G12D, G12R, G12C, G12S, G12V, or G13D) per protocol.

Overall Survival

PFS in the ITT Analysis Set was tested at a significance level of 5% conditional on a significant treatment effect on overall survival in the ITT Analysis Set.

Progression-free Survival

Overall survival in the Wild-type RAS Efficacy Analysis Set was compared at a significance level of 5% conditional on a significant treatment effect for progression-free survival in the ITT Analysis Set.

Wild-type RAS Efficacy Analysis Set (subset of participants in the ITT Analysis Set without mutation in exon 2, 3, and 4 of KRAS or NRAS)

Overall Survival in Participants With Wild-type RAS

PFS in the Wild-type RAS Efficacy Analysis Set was to be compared at a significance level of 5% if overall survival in the wild-type RAS Efficacy Anaysis Set demonstrated a significant treatment effect.

Progression Free Survival (PFS) in Participants With Wild-type RAS

ORR was not formally tested and the p-values are descriptive only. An exact test was used to test the hypothesis that the common odds ratio for panitumumab plus BSC relative to BSC alone for the objective response is equal to 1.0 stratified by the randomization factors.

Objective Response Rate

Objective Response Rate in Participants With Wild-type RAS

Any adverse event (AE)

AE with worst grade of 3

AE with worst grade of 4

AE with worst grade of 5

Serious adverse event (SAE)

AE leading to discontinuation of panitumumab

Treatment-related adverse event (TRAE)

Treatment-related AE with worst grade of 3

Treatment-related AE with worst grade of 4

Treatment-related AE with worst grade of 5

Serious treatment-related AE

TRAE leading to discontinuation of panitumumab

Safety Analysis Set (all randomized participants)

Number of Participants With Adverse Events (AEs)

QTcF

QTcB

QTc Analysis Set is defined as the subset of participants in the Safety Analysis Set who received at least one panitumumab dose and were enrolled at the limited number of sites participating in QTc evaluation and had baseline and at least 1 post-baseline QTc assessment.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Comparison of Survival Benefit of Panitumumab With Supportive Care to Best Supportive Care Alone in Patients With Metastatic Colorectal Cancer	NCT01412957	Metastatic Colo...	Best Supportive... Panitumumab	18 Years -	Amgen
Comparison of Survival Benefit of Panitumumab With Supportive Care to Best Supportive Care Alone in Patients With Metastatic Colorectal Cancer	NCT01412957	Metastatic Colo...	Best Supportive... Panitumumab	18 Years -	Amgen

Spots Global Cancer Trial Database for chemorefractory