Clinical trial NCT01412957: Comparison of Survival Benefit of Panitumumab With Supportive Care to Best Supportive Care Alone in Patients With Metastatic Colorectal Cancer
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Metastatic Colorectal Cancer
Keywords: Best Supportive Care
Panitumumab
Chemorefractory
Wild-type KRAS
Overall Survival
Phase 3
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2011-08-09
Enrollment: 377
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 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.


Eligibility criteria: Inclusion Criteria:

* Diagnosis of metastatic colorectal cancer (CRC)
* Wild-type (without mutation in codons 12 and 13) KRAS gene in tumor tissue confirmed by a central laboratory
* Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2
* At least 1 measurable or non-measurable lesion per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 guidelines.
* Treatment failure (defined as failure due to either disease progression \[clinical or radiological\] or toxicity \[treatment intolerance\]) of a prior regimen containing irinotecan for metastatic disease and a prior regimen containing oxaliplatin for metastatic disease. Oxaliplatin and irinotecan may have been administered sequentially or in combination.

  * Disease relapse within 6 months after completing adjuvant chemotherapy (with either an irinotecan or oxaliplatin containing regimen) will also be considered as treatment failure of a prior regimen for metastatic disease
* Must have previously received a thymidylate synthase inhibitor (eg, fluorouracil, capecitabine, raltitrexed, or fluorouracil-uracil) at any point for treatment of CRC
* Man or woman at least 18 years of age
* Adequate hematologic, renal, hepatic and metabolic function
* Negative pregnancy test within 72 hours before randomization (for women of childbearing potential only)
* Subject or subject's legally acceptable representative has provided informed consent.
* Other protocol-specified criteria may apply

Exclusion Criteria:

* Symptomatic brain metastases requiring treatment
* History of another primary cancer within 5 years of randomization
* 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) within 21 days before randomization
* Radiotherapy within 14 days before randomization.
* Exclusion Criteria for corrected QT (QTc) Evaluation Subpart of the Study: Prolongation of QT/QTc interval \> 450 milliseconds at screening
* Other protocol-specified criteria may apply

Primary outcomes:
measure: Overall Survival
timeFrame: From randomization to the last on-study or long-term follow-up visit, as of the data cut-off date of 10 June 2014. The median follow-up time was 34.9 weeks (panitumumab plus BSC: 41.0 weeks; BSC alone: 25.5 weeks).
Secondary outcomes:
measure: Progression-free Survival
timeFrame: From randomization to the last on-study or long-term follow-up visit, as of the data cut-off date of 10 June 2014. The median follow-up time was 34.9 weeks (panitumumab plus BSC: 41.0 weeks; BSC alone: 25.5 weeks).
measure: Overall Survival in Participants With Wild-type RAS
timeFrame: From randomization to the last on-study or long-term follow-up visit, as of the data cut-off date of 10 June 2014. The median follow-up time was 36.1 weeks (panitumumab plus BSC: 43.7 weeks; BSC alone: 23.6 weeks).
measure: Progression Free Survival (PFS) in Participants With Wild-type RAS
timeFrame: From randomization to the last on-study or long-term follow-up visit, as of the data cut-off date of 10 June 2014. The median follow-up time was 36.1 weeks (panitumumab plus BSC: 43.7 weeks; BSC alone: 23.6 weeks).
measure: Objective Response Rate
timeFrame: Response was assessed at Week 4, Week 8, and then every 8 weeks until the data cut-off date of 10 June 2014. The median follow-up time was 34.9 weeks (panitumumab plus BSC: 41.0 weeks; BSC alone: 25.5 weeks).
measure: Objective Response Rate in Participants With Wild-type RAS
timeFrame: Response was assessed at Week 4, Week 8, and then every 8 weeks until the data cut-off date of 10 June 2014. The median follow-up time was 36.1 weeks (panitumumab plus BSC: 43.7 weeks; BSC alone: 23.6 weeks).
measure: Number of Participants With Adverse Events (AEs)
timeFrame: From first dose until 30 days after last dose; median safety reporting periods were 4.2 months and 2.2 months for panitumumab plus BSC arm and BSC alone arm, respectively.
measure: Maximum Post-baseline Change From Baseline in Corrected QT (QTc) Interval
timeFrame: Baseline (pre-dose), Week 1 and Week 7 (post-dose) and 4 weeks after the last dose (Safety Follow-up visit)
Other outcomes:
Locations:
city: Curitiba
country: Brazil
facility: Research Site
state: Paraná
city: Natal
country: Brazil
facility: Research Site
state: Rio Grande do Norte
city: Ijui
country: Brazil
facility: Research Site
state: Rio Grande do Sul
city: Porto Alegre
country: Brazil
facility: Research Site
state: Rio Grande do Sul
city: Greenfield Park
country: Canada
facility: Research Site
state: Quebec
city: Montreal
country: Canada
facility: Research Site
state: Quebec
city: Montreal
country: Canada
facility: Research Site
state: Quebec
city: Québec
country: Canada
facility: Research Site
state: Quebec
city: Trois-Rivières
country: Canada
facility: Research Site
state: Quebec
city: Quebec
country: Canada
facility: Research Site
city: Temuco
country: Chile
facility: Research Site
state: Cautín
city: Vina del Mar
country: Chile
facility: Research Site
state: Valparaíso
city: Fuzhou
country: China
facility: Research Site
state: Fujian
city: Fuzhou
country: China
facility: Research Site
state: Fujian
city: Shijiazhuang
country: China
facility: Research Site
state: Hebei
city: Nanjing
country: China
facility: Research Site
state: Jiangsu
city: Changchun
country: China
facility: Research Site
state: Jilin
city: Shenyang
country: China
facility: Research Site
state: Liaoning
city: Xi An
country: China
facility: Research Site
state: Shaanxi
city: Xi An
country: China
facility: Research Site
state: Shaanxi
city: Beijing
country: China
facility: Research Site
city: Chongqing
country: China
facility: Research Site
city: Chongqing
country: China
facility: Research Site
city: Shanghai
country: China
facility: Research Site
city: Osijek
country: Croatia
facility: Research Site
city: Pula
country: Croatia
facility: Research Site
city: Rijeka
country: Croatia
facility: Research Site
city: Split
country: Croatia
facility: Research Site
city: Zagreb
country: Croatia
facility: Research Site
city: Tallinn
country: Estonia
facility: Research Site
city: Tartu
country: Estonia
facility: Research Site
city: Athens
country: Greece
facility: Research Site
city: Chania
country: Greece
facility: Research Site
city: Hyderabad
country: India
facility: Research Site
state: Andhra Pradesh
city: Visakhapatnam
country: India
facility: Research Site
state: Andhra Pradesh
city: Bangalore
country: India
facility: Research Site
state: Karnataka
city: Kochi
country: India
facility: Research Site
state: Kerala
city: Mumbai
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: Chennai
country: India
facility: Research Site
state: Tamil Nadu
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: 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: Nilai
country: Malaysia
facility: Research Site
state: Negri Sembilan
city: Georgetown
country: Malaysia
facility: Research Site
state: Pinang
city: Kuala Lumpur
country: Malaysia
facility: Research Site
state: Wilayah Persekutuan
city: Kuala Lumpur
country: Malaysia
facility: Research Site
state: Wilayah Persekutuan
city: Mexico City
country: Mexico
facility: Research Site
state: Distrito Federal
city: Mexico
country: Mexico
facility: Research Site
state: Distrito Federal
city: Cuernavaca
country: Mexico
facility: Research Site
state: Morelos
city: Oaxaca
country: Mexico
facility: Research Site
city: Davao City
country: Philippines
facility: Research Site
state: Davao
city: Cebu City
country: Philippines
facility: Research Site
city: Manila
country: Philippines
facility: Research Site
city: Manila
country: Philippines
facility: Research Site
city: Pasay City
country: Philippines
facility: Research Site
city: Bucharest
country: Romania
facility: Research Site
city: Bucharest
country: Romania
facility: Research Site
city: Cluj-Napoca
country: Romania
facility: Research Site
city: Cluj-Napoca
country: Romania
facility: Research Site
city: Cluj-Napoca
country: Romania
facility: Research Site
city: Craiova
country: Romania
facility: Research Site
city: Craiova
country: Romania
facility: Research Site
city: Lasi
country: Romania
facility: Research Site
city: Ploiesti
country: Romania
facility: Research Site
city: Suceava
country: Romania
facility: Research Site
city: Timisoara
country: Romania
facility: Research Site
city: Belgrade
country: Serbia
facility: Research Site
city: Nis
country: Serbia
facility: Research Site
city: Sremska Kamenica
country: Serbia
facility: Research Site
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References:
citation: Kim TW, Elme A, Kusic Z, Park JO, Udrea AA, Kim SY, Ahn JB, Valencia RV, Krishnan S, Bilic A, Manojlovic N, Dong J, Guan X, Lofton-Day C, Jung AS, Vrdoljak E. A phase 3 trial evaluating panitumumab plus best supportive care vs best supportive care in chemorefractory wild-type KRAS or RAS metastatic colorectal cancer. Br J Cancer. 2016 Nov 8;115(10):1206-1214. doi: 10.1038/bjc.2016.309. Epub 2016 Oct 13.