Clinical trial NCT01001377: ASPECCT: A Study of Panitumumab Efficacy and Safety Compared to Cetuximab in Patients With KRAS Wild-Type Metastatic Colorectal Cancer
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Metastatic Colorectal Cancer
Keywords: Panitumumab
Vectibix
Colon Cancer
Colorectal Cancer
Rectal Cancer
Cetuximab
Erbitux
Metastatic
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2009-10-26
Enrollment: 1010
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.


Eligibility 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

Primary outcomes:
measure: Overall Survival
timeFrame: From randomization until the data cut-off date of 5 February 2013. Maximum time on study was 155 weeks.
Secondary outcomes:
measure: Progression-free Survival
timeFrame: From randomization until the data cut-off date of 5 February 2013. Maximum time on study was 155 weeks.
measure: Objective Response
timeFrame: From randomization until the data cut-off date of 5 February 2013. Maximum time on study was 155 weeks.
measure: Duration of Response
timeFrame: From randomization until the data cut-off date of 5 February 2013. Maximum time on study was 155 weeks.
measure: Time to Response
timeFrame: From randomization until the data cut-off date of 5 February 2013. Maximum time on study was 155 weeks.
measure: Time to Treatment Failure
timeFrame: From randomization until the data cut-off date of 5 February 2013. Maximum time on study was 155 weeks.
measure: Change From Baseline in EuroQOL 5 Dimension (EQ-5D) Health State Index Score
timeFrame: From Study Day 1 through the last day of treatment or disease progression, up to Week 85.
measure: Change From Baseline in EuroQOL 5 Dimension (EQ-5D) Visual Analog Scale (VAS)
timeFrame: From Study Day 1 through the last day of treatment or disease progression, up to Week 85.
measure: Change From Baseline in National Comprehensive Cancer Network Functional Assessment of Cancer Therapy Colorectal Symptom Index (NCCN FCSI ) Symptoms Score
timeFrame: From Study Day 1 through the last day of treatment or disease progression, up to Week 85.
measure: Change From Baseline in NCCN FCSI Physical Well-being Scale Score
timeFrame: From Study Day 1 through the last day of treatment or disease progression, up to Week 85.
measure: Change From Baseline in NCCN FCSI Functional Well-being Scale Score
timeFrame: From Study Day 1 through the last day of treatment or disease progression, up to Week 85.
measure: Number of Participants With Adverse Events (AEs)
timeFrame: 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.
Other outcomes:
Locations:
city: Stockton
country: United States
facility: Research Site
state: California
city: Boynton Beach
country: United States
facility: Research Site
state: Florida
city: Wichita
country: United States
facility: Research Site
state: Kansas
city: Temple
country: United States
facility: Research Site
state: Texas
city: Ogden
country: United States
facility: Research Site
state: Utah
city: Liverpool
country: Australia
facility: Research Site
state: New South Wales
city: St Leonards
country: Australia
facility: Research Site
state: New South Wales
city: Wahroonga
country: Australia
facility: Research Site
state: New South Wales
city: Wollongong
country: Australia
facility: Research Site
state: New South Wales
city: Woodville South
country: Australia
facility: Research Site
state: South Australia
city: Ballarat
country: Australia
facility: Research Site
state: Victoria
city: Box Hill
country: Australia
facility: Research Site
state: Victoria
city: Epping
country: Australia
facility: Research Site
state: Victoria
city: Footscray
country: Australia
facility: Research Site
state: Victoria
city: Heidelberg
country: Australia
facility: Research Site
state: Victoria
city: Parkville
country: Australia
facility: Research Site
state: Victoria
city: Edegem
country: Belgium
facility: Research Site
city: Sofia
country: Bulgaria
facility: Research Site
city: Sofia
country: Bulgaria
facility: Research Site
city: Edmonton
country: Canada
facility: Research Site
state: Alberta
city: Halifax
country: Canada
facility: Research Site
state: Nova Scotia
city: Guangzhou
country: China
facility: Research Site
state: Guangdong
city: Guangzhou
country: China
facility: Research Site
state: Guangdong
city: Guangzhou
country: China
facility: Research Site
state: Guangdong
city: Guangzhou
country: China
facility: Research Site
state: Guangdong
city: Harbin
country: China
facility: Research Site
state: Heilongjiang
city: Changsha
country: China
facility: Research Site
state: Hunan
city: Nanjing
country: China
facility: Research Site
state: Jiangsu
city: Changchun
country: China
facility: Research Site
state: Jilin
city: XI An
country: China
facility: Research Site
state: Shaanxi
city: Shanghai
country: China
facility: Research Site
state: Shanghai
city: Chengdu
country: China
facility: Research Site
state: Sichuan
city: Chongqing
country: China
facility: Research Site
state: Sichuan
city: Hangzhou
country: China
facility: Research Site
state: Zhejiang
city: Hangzhou
country: China
facility: Research Site
state: Zhejiang
city: Beijing
country: China
facility: Research Site
city: Beijing
country: China
facility: Research Site
city: Beijing
country: China
facility: Research Site
city: Shanghai
country: China
facility: Research Site
city: Shanghai
country: China
facility: Research Site
city: Shanghai
country: China
facility: Research Site
city: Tianjin
country: China
facility: Research Site
city: Horovice
country: Czechia
facility: Research Site
city: Nova Ves pod Plesi
country: Czechia
facility: Research Site
city: Olomouc
country: Czechia
facility: Research Site
city: Praha 10
country: Czechia
facility: Research Site
city: Pribram
country: Czechia
facility: Research Site
city: Znojmo
country: Czechia
facility: Research Site
city: Besançon Cedex
country: France
facility: Research Site
city: Montbéliard
country: France
facility: Research Site
city: Saint Brieuc
country: France
facility: Research Site
city: Saint Herblain
country: France
facility: Research Site
city: Villejuif cedex
country: France
facility: Research Site
city: Kowloon
country: Hong Kong
facility: Research Site
city: New Territories
country: Hong Kong
facility: Research Site
city: Hyderabad
country: India
facility: Research Site
state: Andhra Pradesh
city: Hyderabad
country: India
facility: Research Site
state: Andhra Pradesh
city: Kochi
country: India
facility: Research Site
state: Kerala
city: Ahmednagar
country: India
facility: Research Site
state: Maharashtra
city: Nagpur
country: India
facility: Research Site
state: Maharashtra
city: Nashik
country: India
facility: Research Site
state: Maharashtra
city: Nashik
country: India
facility: Research Site
state: Maharashtra
city: Pune
country: India
facility: Research Site
state: Maharashtra
city: Jaipur
country: India
facility: Research Site
state: Rajasthan
city: Chennai
country: India
facility: Research Site
state: Tamil Nadu
city: Kolkata
country: India
facility: Research Site
state: West Bengal
city: Beer Sheva
country: Israel
facility: Research Site
city: Jerusalem
country: Israel
facility: Research Site
city: Kfar Saba
country: Israel
facility: Research Site
city: Ramat Gan
country: Israel
facility: Research Site
city: Rehovot
country: Israel
facility: Research Site
city: Ancona
country: Italy
facility: Research Site
city: Cesena
country: Italy
facility: Research Site
city: Cremona
country: Italy
facility: Research Site
city: Faenza RA
country: Italy
facility: Research Site
city: Genova
country: Italy
facility: Research Site
city: Lugo
country: Italy
facility: Research Site
city: Meldola FC
country: Italy
facility: Research Site
city: Ravenna
country: Italy
facility: Research Site
city: Rimini
country: Italy
facility: Research Site
city: Torino
country: Italy
facility: Research Site
city: Goyang-si, Gyeonggi-do
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Daugavpils
country: Latvia
facility: Research Site
city: Riga
country: Latvia
facility: Research Site
city: Riga
country: Latvia
facility: Research Site
city: Kaunas
country: Lithuania
facility: Research Site
city: Vilnius
country: Lithuania
facility: Research Site
city: Kota Bharu
country: Malaysia
facility: Research Site
state: Kelantan
city: Kota Kinabalu
country: Malaysia
facility: Research Site
state: Sabah
city: Kuala Lumpur
country: Malaysia
facility: Research Site
state: Wilayah Persekutuan
city: Kuala Lumpur
country: Malaysia
facility: Research Site
state: Wilayah Persekutuan
city: Rotterdam
country: Netherlands
facility: Research Site
city: Lima
country: Peru
facility: Research Site
city: Lima
country: Peru
facility: Research Site
city: Lima
country: Peru
facility: Research Site
city: Cebu City
country: Philippines
facility: Research Site
city: Manila
country: Philippines
facility: Research Site
city: Quezon City
country: Philippines
facility: Research Site
city: Elblag
country: Poland
facility: Research Site
city: Gdansk
country: Poland
facility: Research Site
city: Jelenia Gora
country: Poland
facility: Research Site
city: Poznan
country: Poland
facility: Research Site
city: Szczecin
country: Poland
facility: Research Site
city: Warszawa
country: Poland
facility: Research Site
city: Warszawa
country: Poland
facility: Research Site
city: Warszawa
country: Poland
facility: Research Site
city: Bucharest
country: Romania
facility: Research Site
city: Sibiu
country: Romania
facility: Research Site
city: Moscow
country: Russian Federation
facility: Research Site
city: Moscow
country: Russian Federation
facility: Research Site
city: Saint Petersburg
country: Russian Federation
facility: Research Site
city: Saint-Petersburg
country: Russian Federation
facility: Research Site
city: Saint-Petersburg
country: Russian Federation
facility: Research Site
city: Nis
country: Serbia
facility: Research Site
city: Sremska Kamenica
country: Serbia
facility: Research Site
city: Singapore
country: Singapore
facility: Research Site
city: Singapore
country: Singapore
facility: Research Site
city: Bardejov
country: Slovakia
facility: Research Site
city: Bratislava
country: Slovakia
facility: Research Site
city: Nitra
country: Slovakia
facility: Research Site
city: Groenkloof
country: South Africa
facility: Research Site
state: Gauteng
city: Johannesburg
country: South Africa
facility: Research Site
state: Gauteng
city: Kraaifontein
country: South Africa
facility: Research Site
state: Western Cape
city: Johannesburg
country: South Africa
facility: Research Site
city: Port Elizabeth
country: South Africa
facility: Research Site
city: Göteborg
country: Sweden
facility: Research Site
city: Linköping
country: Sweden
facility: Research Site
city: Lund
country: Sweden
facility: Research Site
city: Uppsala
country: Sweden
facility: Research Site
city: Västerås
country: Sweden
facility: Research Site
city: Växjö
country: Sweden
facility: Research Site
city: Putzu City
country: Taiwan
facility: Research Site
state: Chiayi
city: Keelung
country: Taiwan
facility: Research Site
city: Tainan
country: Taiwan
facility: Research Site
city: Taipei
country: Taiwan
facility: Research Site
city: Taoyuan
country: Taiwan
facility: Research Site
city: Belfast
country: United Kingdom
facility: Research Site
city: Bristol
country: United Kingdom
facility: Research Site
city: Cardiff
country: United Kingdom
facility: Research Site
city: Guildford
country: United Kingdom
facility: Research Site
city: Leicester
country: United Kingdom
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
city: Maidstone
country: United Kingdom
facility: Research Site
city: Manchester
country: United Kingdom
facility: Research Site
city: Oxford
country: United Kingdom
facility: Research Site
city: Sutton
country: United Kingdom
facility: Research Site
city: Wolverhampton
country: United Kingdom
facility: Research Site
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References:
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.
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.
citation: 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.
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.
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.
citation: Taniguchi H, Yamanaka T, Sakai D, Muro K, Yamazaki K, Nakata S, Kimura H, Ruff P, Kim TW, Peeters M, Price T. Efficacy of Panitumumab and Cetuximab in Patients with Colorectal Cancer Previously Treated with Bevacizumab; a Combined Analysis of Individual Patient Data from ASPECCT and WJOG6510G. Cancers (Basel). 2020 Jun 28;12(7):1715. doi: 10.3390/cancers12071715.
citation: Graham CN, Maglinte GA, Schwartzberg LS, Price TJ, Knox HN, Hechmati G, Hjelmgren J, Barber B, Fakih MG. Economic Analysis of Panitumumab Compared With Cetuximab in Patients With Wild-type KRAS Metastatic Colorectal Cancer That Progressed After Standard Chemotherapy. Clin Ther. 2016 Jun;38(6):1376-1391. doi: 10.1016/j.clinthera.2016.03.023. Epub 2016 Apr 13.