ASPECCT: A Study of Panitumumab Efficacy and Safety Compared to Cetuximab in Patients With KRAS Wild-Type Metastatic Colorectal Cancer

Study Overview
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Brief Summary
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The primary objective of this study is to compare the effect of panitumumab versus cetuximab on overall survival (OS) for chemorefractory metastatic colorectal cancer (mCRC) among patients with wild-type Kirsten rat Sarcoma-2 virus (KRAS) tumors.

Official Title
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A Randomized, Multicenter, Open-label, Phase 3 Study to Compare the Efficacy and Safety of Panitumumab and Cetuximab in Subjects With Previously Treated, Wild-type KRAS, Metastatic Colorectal Cancer

Conditions
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Metastatic Colorectal Cancer

Intervention / Treatment
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* Drug: Cetuximab
* Drug: Panitumumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically or cytologically confirmed diagnosis of adenocarcinoma of the colon or rectum, metastatic disease Wild-type KRAS tumor status Eastern Cooperative Oncology Group (ECOG) score of 0, 1 or 2 Must have failed a prior regimen containing irinotecan for metastatic disease and a prior regimen containing oxaliplatin for metastatic disease Must have previously received a thymidylate synthase inhibitor (eg, fluorouracil, capecitabine, raltitrexed, or fluorouracil-uracil) at any point for treatment of colorectal cancer (CRC) Adequate hematologic, renal, hepatic and metabolic function Exclusion Criteria: Symptomatic brain metastases requiring treatment Prior anti-epidermal growth factor receptor (EGFr) antibody therapy (eg, panitumumab or cetuximab) or treatment with small molecule EGFr inhibitors (eg, gefitinib, erlotinib, lapatinib) Antitumor therapy (eg, chemotherapy, hormonal therapy, immunotherapy, antibody therapy, radiotherapy), or investigational agent or therapy ≤ 30 days before randomization. Clinically significant cardiovascular disease Active infection requiring systemic treatment or any uncontrolled infection ≤14 days prior to randomization

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Cetuximab<br>Cetuximab 400 mg/m^2 as an initial dose, followed by 250 mg/m^2 intravenously (IV) every 7 days. Participants were treated until disease progression, intolerability, withdrawal of consent, or death. | Drug: Cetuximab<br>* Administered by intravenous infusion<br>* Other names: Erbitux;|
| Experimental: Panitumumab<br>Panitumumab 6 mg/kg IV every 14 days. Participants were treated until disease progression, intolerability, withdrawal of consent, or death. | Drug: Panitumumab<br>* Administered by intravenous infusion<br>* Other names: Vectibix;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival | Overall survival is the time from the date of randomization until the date of death. Participants who had not died by the analysis data cut-off date were censored at their last contact date. | From randomization until the data cut-off date of 5 February 2013. Maximum time on study was 155 weeks. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival | Progression free survival (PFS) is the time from the date of randomization to the date of disease progression per the Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1 or death. Participants alive and not meeting criteria for progression by the analysis data cut-off date were censored at their last evaluable disease assessment date. Progression is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study based on all target lesions recorded since the treatment started (the sum must also demonstrate an absolute increase of at least 5 mm), or unequivocal progression of existing non-target lesions, or any new lesions. | From randomization until the data cut-off date of 5 February 2013. Maximum time on study was 155 weeks. | 
| Objective Response | Objective response is either a complete response (CR) or partial response (PR) per RECIST version 1.1. All participants that did not meet the criteria for an objective response by the analysis cut-off date were considered non-responders. CR: Disappearance of all target lesions, any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm, and disappearance of all non-target lesions, and no new lesions. PR: Disappearance of all target lesions, persistence of one or more non-target lesions not qualifying for either CR or progressive disease, or, at least a 30% decrease in the sum of diameters of target lesions with no unequivocal progression of existing non-target lesions and no new lesions. | From randomization until the data cut-off date of 5 February 2013. Maximum time on study was 155 weeks. | 
| Duration of Response | Duration of response (DOR), calculated only for those participants with an objective response, is the time from first objective response to disease progression per the RECIST v1.1 or death. Participants not meeting criteria for progression or who died by the analysis data cutoff date were censored at their last evaluable disease assessment date. | From randomization until the data cut-off date of 5 February 2013. Maximum time on study was 155 weeks. | 
| Time to Response | Time to response (TTR), calculated for those participants with an objective response, is defined as the time from the randomization date to the date of first objective response. | From randomization until the data cut-off date of 5 February 2013. Maximum time on study was 155 weeks. | 
| Time to Treatment Failure | Time to treatment failure (TTF) is the time from randomization date to date that the decision was made to end the treatment period for any reason; participants who remained in the treatment period at the time of analysis were censored at the date of the last on-study assessment. | From randomization until the data cut-off date of 5 February 2013. Maximum time on study was 155 weeks. | 
| Change From Baseline in EuroQOL 5 Dimension (EQ-5D) Health State Index Score | The EQ-5D is a standardized instrument for use as a generic measure of health outcome. The health state index measures the following 5 health dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension contains 3 levels of response to reflect degree of problems participants have experienced: no problem (1), some problem (2) and extreme problems (3). The health states for each respondent are converted into a single index number using a specified set of weights. Resulting scores can range from 1.0 and -0.594. A higher score indicates a more preferred health status with 1.0 representing perfect health and 0 representing death. Negative scores are possible and represent health states regarded as less preferable than death (0). Repeated measures mixed model includes treatment, geographic region, ECOG score, assessment week, and treatment by assessment week interaction as fixed effects, and participants a random effect. | From Study Day 1 through the last day of treatment or disease progression, up to Week 85. | 
| Change From Baseline in EuroQOL 5 Dimension (EQ-5D) Visual Analog Scale (VAS) | The EQ-5D is a standardized instrument for use as a generic measure of health outcome. The VAS asks respondents to rate their present health status on a 0 - 100 scale, with 0 labeled as Worst imaginable health state and 100 labeled as Best imaginable health state. The VAS score is determined by observing the point at which the participant's hand drawn line intersects the scale. | From Study Day 1 through the last day of treatment or disease progression, up to Week 85. | 
| Change From Baseline in National Comprehensive Cancer Network Functional Assessment of Cancer Therapy Colorectal Symptom Index (NCCN FCSI ) Symptoms Score | The FCSI consists of 9 questions comprising the most important symptoms associated with colorectal cancer, including energy, pain, weight, diarrhea, nausea, swelling or cramps in the stomach area, appetite, ability to enjoy life, and overall quality of life. The 9 questions are combined in three algorithms to provide information for 3 domains: colorectal cancer symptoms, physical well-being, and functional well-being. Each of the 9 items are scored from 0 to 4 representing Not at All through to Very Much True. The raw score for all items is transformed to a 0-100 scale, and the average for each of the 3 subscales is calculated; high scores illustrate an improved state (e.g. able to enjoy life more). | From Study Day 1 through the last day of treatment or disease progression, up to Week 85. | 
| Change From Baseline in NCCN FCSI Physical Well-being Scale Score | The FCSI consists of 9 questions comprising the most important symptoms associated with colorectal cancer, including energy, pain, weight, diarrhea, nausea, swelling or cramps in the stomach area, appetite, ability to enjoy life, and overall quality of life. The 9 questions are combined in three algorithms to provide information for 3 domains: colorectal cancer symptoms, physical well-being, and functional well-being. Each of the 9 items are scored from 0 to 4 representing Not at All through to Very Much True. The raw score for all items is transformed to a 0-100 scale, and the average for each of the 3 subscales is calculated; high scores illustrate an improved state (e.g. able to enjoy life more). | From Study Day 1 through the last day of treatment or disease progression, up to Week 85. | 
| Change From Baseline in NCCN FCSI Functional Well-being Scale Score | The FCSI consists of 9 questions comprising the most important symptoms associated with colorectal cancer, including energy, pain, weight, diarrhea, nausea, swelling or cramps in the stomach area, appetite, ability to enjoy life, and overall quality of life. The 9 questions are combined in three algorithms to provide information for 3 domains: colorectal cancer symptoms, physical well-being, and functional well-being. Each of the 9 items are scored from 0 to 4 representing Not at All through to Very Much True. The raw score for all items is transformed to a 0-100 scale, and the average for each of the 3 subscales is calculated; high scores illustrate an improved state (e.g. able to enjoy life more). | From Study Day 1 through the last day of treatment or disease progression, up to Week 85. | 
| Number of Participants With Adverse Events (AEs) | Serious adverse events include any event that is fatal, life threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, a congenital anomaly/birth defect, or other significant medical hazard. Treatment-related AEs are those the investigator considered as a reasonable possibility to have been caused by study drug. | From the day of the first dose of study therapy through 30 days since the last dose. Maximum time on study treatment was 130 weeks. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Panitumumab, Vectibix, Colon Cancer, Colorectal Cancer, Rectal Cancer, Cetuximab, Erbitux, Metastatic