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

Metastatic Colorectal Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01001377
• Other study ID #: 20080763
• Secondary ID: ASPECCT2009-0107
• Status: Completed
• Phase: Phase 3
• Start date: February 2, 2010
• Est. completion date: March 7, 2017

Study information

• Verified date: September 2022
• Source: Amgen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1010
• Est. completion date: March 7, 2017
• Est. primary completion date: February 5, 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Colorectal Neoplasms
• Metastatic Colorectal Cancer

Intervention

Drug:
• Cetuximab
Administered by intravenous infusion
• Panitumumab
Administered by intravenous infusion

Locations

Country	Name	City	State
Australia	Research Site	Ballarat	Victoria
Australia	Research Site	Box Hill	Victoria
Australia	Research Site	Epping	Victoria
Australia	Research Site	Footscray	Victoria
Australia	Research Site	Heidelberg	Victoria
Australia	Research Site	Liverpool	New South Wales
Australia	Research Site	Parkville	Victoria
Australia	Research Site	St Leonards	New South Wales
Australia	Research Site	Wahroonga	New South Wales
Australia	Research Site	Wollongong	New South Wales
Australia	Research Site	Woodville South	South Australia
Belgium	Research Site	Edegem
Bulgaria	Research Site	Sofia
Bulgaria	Research Site	Sofia
Canada	Research Site	Edmonton	Alberta
Canada	Research Site	Halifax	Nova Scotia
China	Research Site	Beijing
China	Research Site	Beijing
China	Research Site	Beijing
China	Research Site	Changchun	Jilin
China	Research Site	Changsha	Hunan
China	Research Site	Chengdu	Sichuan
China	Research Site	Chongqing	Sichuan
China	Research Site	Guangzhou	Guangdong
China	Research Site	Guangzhou	Guangdong
China	Research Site	Guangzhou	Guangdong
China	Research Site	Guangzhou	Guangdong
China	Research Site	Hangzhou	Zhejiang
China	Research Site	Hangzhou	Zhejiang
China	Research Site	Harbin	Heilongjiang
China	Research Site	Nanjing	Jiangsu
China	Research Site	Shanghai
China	Research Site	Shanghai
China	Research Site	Shanghai
China	Research Site	Shanghai	Shanghai
China	Research Site	Tianjin
China	Research Site	XI An	Shaanxi
Czechia	Research Site	Horovice
Czechia	Research Site	Nova Ves pod Plesi
Czechia	Research Site	Olomouc
Czechia	Research Site	Praha 10
Czechia	Research Site	Pribram
Czechia	Research Site	Znojmo
France	Research Site	Besançon Cedex
France	Research Site	Montbéliard
France	Research Site	Saint Brieuc
France	Research Site	Saint Herblain
France	Research Site	Villejuif cedex
Hong Kong	Research Site	Kowloon
Hong Kong	Research Site	New Territories
India	Research Site	Ahmednagar	Maharashtra
India	Research Site	Chennai	Tamil Nadu
India	Research Site	Hyderabad	Andhra Pradesh
India	Research Site	Hyderabad	Andhra Pradesh
India	Research Site	Jaipur	Rajasthan
India	Research Site	Kochi	Kerala
India	Research Site	Kolkata	West Bengal
India	Research Site	Nagpur	Maharashtra
India	Research Site	Nashik	Maharashtra
India	Research Site	Nashik	Maharashtra
India	Research Site	Pune	Maharashtra
Israel	Research Site	Beer Sheva
Israel	Research Site	Jerusalem
Israel	Research Site	Kfar Saba
Israel	Research Site	Ramat Gan
Israel	Research Site	Rehovot
Italy	Research Site	Ancona
Italy	Research Site	Cesena
Italy	Research Site	Cremona
Italy	Research Site	Faenza RA
Italy	Research Site	Genova
Italy	Research Site	Lugo
Italy	Research Site	Meldola FC
Italy	Research Site	Ravenna
Italy	Research Site	Rimini
Italy	Research Site	Torino
Korea, Republic of	Research Site	Goyang-si, Gyeonggi-do
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Latvia	Research Site	Daugavpils
Latvia	Research Site	Riga
Latvia	Research Site	Riga
Lithuania	Research Site	Kaunas
Lithuania	Research Site	Vilnius
Malaysia	Research Site	Kota Bharu	Kelantan
Malaysia	Research Site	Kota Kinabalu	Sabah
Malaysia	Research Site	Kuala Lumpur	Wilayah Persekutuan
Malaysia	Research Site	Kuala Lumpur	Wilayah Persekutuan
Netherlands	Research Site	Rotterdam
Peru	Research Site	Lima
Peru	Research Site	Lima
Peru	Research Site	Lima
Philippines	Research Site	Cebu City
Philippines	Research Site	Manila
Philippines	Research Site	Quezon City
Poland	Research Site	Elblag
Poland	Research Site	Gdansk
Poland	Research Site	Jelenia Gora
Poland	Research Site	Poznan
Poland	Research Site	Szczecin
Poland	Research Site	Warszawa
Poland	Research Site	Warszawa
Poland	Research Site	Warszawa
Romania	Research Site	Bucharest
Romania	Research Site	Sibiu
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	Saint Petersburg
Russian Federation	Research Site	Saint-Petersburg
Russian Federation	Research Site	Saint-Petersburg
Serbia	Research Site	Nis
Serbia	Research Site	Sremska Kamenica
Singapore	Research Site	Singapore
Singapore	Research Site	Singapore
Slovakia	Research Site	Bardejov
Slovakia	Research Site	Bratislava
Slovakia	Research Site	Nitra
South Africa	Research Site	Groenkloof	Gauteng
South Africa	Research Site	Johannesburg	Gauteng
South Africa	Research Site	Johannesburg
South Africa	Research Site	Kraaifontein	Western Cape
South Africa	Research Site	Port Elizabeth
Sweden	Research Site	Göteborg
Sweden	Research Site	Linköping
Sweden	Research Site	Lund
Sweden	Research Site	Uppsala
Sweden	Research Site	Västerås
Sweden	Research Site	Växjö
Taiwan	Research Site	Keelung
Taiwan	Research Site	Putzu City	Chiayi
Taiwan	Research Site	Tainan
Taiwan	Research Site	Taipei
Taiwan	Research Site	Taoyuan
United Kingdom	Research Site	Belfast
United Kingdom	Research Site	Bristol
United Kingdom	Research Site	Cardiff
United Kingdom	Research Site	Guildford
United Kingdom	Research Site	Leicester
United Kingdom	Research Site	London
United Kingdom	Research Site	Maidstone
United Kingdom	Research Site	Manchester
United Kingdom	Research Site	Oxford
United Kingdom	Research Site	Sutton
United Kingdom	Research Site	Wolverhampton
United States	Research Site	Boynton Beach	Florida
United States	Research Site	Ogden	Utah
United States	Research Site	Stockton	California
United States	Research Site	Temple	Texas
United States	Research Site	Wichita	Kansas

Sponsors (1)

Lead Sponsor	Collaborator
Amgen

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Bulgaria,  Canada,  China,  Czechia,  France,  Hong Kong,  India,  Israel,  Italy,  Korea, Republic of,  Latvia,  Lithuania,  Malaysia,  Netherlands,  Peru,  Philippines,  Poland,  Romania,  Russian Federation,  Serbia,  Singapore,  Slovakia,  South Africa,  Sweden,  Taiwan,  United Kingdom, 

References & Publications (5)

Kim TW, Peeters M, Thomas A, Gibbs P, Hool K, Zhang J, Ang AL, Bach BA, Price T. Impact of Emergent Circulating Tumor DNA RAS Mutation in Panitumumab-Treated Chemoresistant Metastatic Colorectal Cancer. Clin Cancer Res. 2018 Nov 15;24(22):5602-5609. doi: 10.1158/1078-0432.CCR-17-3377. Epub 2018 Jun 13. — View Citation

Peeters M, Price T, Boedigheimer M, Kim TW, Ruff P, Gibbs P, Thomas A, Demonty G, Hool K, Ang A. Evaluation of Emergent Mutations in Circulating Cell-Free DNA and Clinical Outcomes in Patients with Metastatic Colorectal Cancer Treated with Panitumumab in the ASPECCT Study. Clin Cancer Res. 2019 Feb 15;25(4):1216-1225. doi: 10.1158/1078-0432.CCR-18-2072. Epub 2018 Nov 28. — View Citation

Price T, Ang A, Boedigheimer M, Kim TW, Li J, Cascinu S, Ruff P, Satya Suresh A, Thomas A, Tjulandin S, Peeters M. Frequency of S492R mutations in the epidermal growth factor receptor: analysis of plasma DNA from patients with metastatic colorectal cancer treated with panitumumab or cetuximab monotherapy. Cancer Biol Ther. 2020 Oct 2;21(10):891-898. doi: 10.1080/15384047.2020.1798695. Epub 2020 Oct 7. — View Citation

Price T, Kim TW, Li J, Cascinu S, Ruff P, Suresh AS, Thomas A, Tjulandin S, Guan X, Peeters M. Final results and outcomes by prior bevacizumab exposure, skin toxicity, and hypomagnesaemia from ASPECCT: randomized phase 3 non-inferiority study of panitumumab versus cetuximab in chemorefractory wild-type KRAS exon 2 metastatic colorectal cancer. Eur J Cancer. 2016 Nov;68:51-59. doi: 10.1016/j.ejca.2016.08.010. Epub 2016 Oct 5. — View Citation

Price TJ, Peeters M, Kim TW, Li J, Cascinu S, Ruff P, Suresh AS, Thomas A, Tjulandin S, Zhang K, Murugappan S, Sidhu R. Panitumumab versus cetuximab in patients with chemotherapy-refractory wild-type KRAS exon 2 metastatic colorectal cancer (ASPECCT): a randomised, multicentre, open-label, non-inferiority phase 3 study. Lancet Oncol. 2014 May;15(6):569-79. doi: 10.1016/S1470-2045(14)70118-4. Epub 2014 Apr 14. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.

External Links

•   AmgenTrials clinical trials website