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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Amgen
ClinicalTrials.gov Identifier:
NCT01001377
First received: October 22, 2009
Last updated: April 15, 2014
Last verified: April 2014
  Purpose

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.


Condition Intervention Phase
Metastatic Colorectal Cancer
Drug: Cetuximab
Drug: Panitumumab
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Amgen:

Primary Outcome Measures:
  • Overall Survival [ Time Frame: From randomization until the data cut-off date of 5 February 2013. Maximum time on study was 155 weeks. ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Progression-free Survival [ Time Frame: From randomization until the data cut-off date of 5 February 2013. Maximum time on study was 155 weeks. ] [ Designated as safety issue: No ]

    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.


  • Objective Response [ Time Frame: From randomization until the data cut-off date of 5 February 2013. Maximum time on study was 155 weeks. ] [ Designated as safety issue: No ]
    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.

  • Duration of Response [ Time Frame: From randomization until the data cut-off date of 5 February 2013. Maximum time on study was 155 weeks. ] [ Designated as safety issue: No ]
    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.

  • Time to Response [ Time Frame: From randomization until the data cut-off date of 5 February 2013. Maximum time on study was 155 weeks. ] [ Designated as safety issue: No ]
    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.

  • Time to Treatment Failure [ Time Frame: From randomization until the data cut-off date of 5 February 2013. Maximum time on study was 155 weeks. ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline in EuroQOL 5 Dimension (EQ-5D) Health State Index Score [ Time Frame: From Study Day 1 through the last day of treatment or disease progression, up to Week 85. ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline in EuroQOL 5 Dimension (EQ-5D) Visual Analog Scale (VAS) [ Time Frame: From Study Day 1 through the last day of treatment or disease progression, up to Week 85. ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline in National Comprehensive Cancer Network Functional Assessment of Cancer Therapy Colorectal Symptom Index (NCCN FCSI ) Symptoms Score [ Time Frame: From Study Day 1 through the last day of treatment or disease progression, up to Week 85. ] [ Designated as safety issue: No ]
    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).

  • Change From Baseline in NCCN FCSI Physical Well-being Scale Score [ Time Frame: From Study Day 1 through the last day of treatment or disease progression, up to Week 85. ] [ Designated as safety issue: No ]
    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).

  • Change From Baseline in NCCN FCSI Functional Well-being Scale Score [ Time Frame: From Study Day 1 through the last day of treatment or disease progression, up to Week 85. ] [ Designated as safety issue: No ]
    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).

  • Number of Participants With Adverse Events (AEs) [ Time Frame: 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. ] [ Designated as safety issue: Yes ]
    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.


Enrollment: 1010
Study Start Date: February 2010
Estimated Study Completion Date: September 2014
Primary Completion Date: February 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Cetuximab

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
Administered by intravenous infusion
Other Name: Erbitux
Experimental: Panitumumab
Panitumumab 6 mg/kg IV every 14 days. Participants were treated until disease progression, intolerability, withdrawal of consent, or death.
Drug: Panitumumab
Administered by intravenous infusion
Other Name: Vectibix

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01001377

  Show 152 Study Locations
Sponsors and Collaborators
Amgen
Investigators
Study Director: MD Amgen
  More Information

Additional Information:
No publications provided

Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT01001377     History of Changes
Other Study ID Numbers: 20080763, ASPECCT, 2009-010715-32
Study First Received: October 22, 2009
Results First Received: February 3, 2014
Last Updated: April 15, 2014
Health Authority: United States: Food and Drug Administration
India: Central Drugs Standard Control Organization
Israel: Ministry of Health
South Korea: Korea Food & Drug Administration
Taiwan: Department of Health
South Africa: Department of Health
Serbia: Medicine and Medical Devices Agency of Serbia
Peru: Ministry of Health
Australia: Department of Health and Ageing Therapeutic Goods Administration
Belgium: Federal Agency for Medicines and Health Products, FAMHP
Bulgaria: Bulgarian Drug Agency
Canada: Health Canada
China: cFDA
Czech Republic: State Institute for Drug Control
EU: CHMP
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Hong Kong: Department of Health
Italy: Ethics Committee
Latvia: State Agency of Medicines
Lithuania: State Medicines Control Agency of Lithuania
Malaysia: National Pharmaceutical Control Bureau
Netherlands:Centrale Commissie Mensgebonden Onderzoek (CCMO)
Phillippines: the Bureau of Food and Drugs
Poland: Ministry of Health
Romania: National Medicines Agency
Russia: Ministry of Health of the Russian Federation
Singapore: Health Science Authority
Slovakia: State Institiute for Drug Control
South Korea: Korea Food and Drug Administration
Sweden: Medical Products Agency
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Amgen:
Panitumumab
Vectibix
Colon Cancer
Colorectal Cancer
Rectal Cancer
Cetuximab
Erbitux
Metastatic

Additional relevant MeSH terms:
Colorectal Neoplasms
Colonic Diseases
Digestive System Diseases
Digestive System Neoplasms
Gastrointestinal Diseases
Gastrointestinal Neoplasms
Intestinal Diseases
Intestinal Neoplasms
Neoplasms
Neoplasms by Site
Rectal Diseases
Antibodies, Monoclonal
Cetuximab
Antineoplastic Agents
Immunologic Factors
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014