Comparison of Survival Benefit of Panitumumab With Supportive Care to Best Supportive Care Alone in Patients With Metastatic Colorectal Cancer

Metastatic Colorectal Cancer Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01412957
• Other study ID #: 20100007
• Secondary ID: 2010-022951-49
• Status: Active, not recruiting
• Phase: Phase 3
• First received: March 31, 2011
• Last updated: April 7, 2016
• Start date: November 2011
• Est. completion date: June 2016

Study information

• Verified date: April 2016
• Source: Amgen
• Contact: n/a
• Is FDA regulated: No
• Health authority: EU: CHMPUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 377
• Est. completion date: June 2016
• Est. primary completion date: June 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Colorectal Neoplasms
• Metastatic Colorectal Cancer

Intervention

Other:
• Best Supportive Care (BSC)
BSC was defined as the best palliative care available as judged appropriate by the investigator and according to institutional guidelines and could include antibiotics, analgesics, radiation therapy for pain control (limited to bone metastases), corticosteroids, transfusions, psychotherapy, growth factors, palliative surgery, or any other symptomatic therapy as clinically indicated.

Drug:
• Panitumumab
Administered intravenously

Locations

Country	Name	City	State
Brazil	Research Site	Curitiba	Paraná
Brazil	Research Site	Ijui	Rio Grande do Sul
Brazil	Research Site	Natal	Rio Grande do Norte
Brazil	Research Site	Porto Alegre	Rio Grande do Sul
Canada	Research Site	Greenfield Park	Quebec
Canada	Research Site	Montreal	Quebec
Canada	Research Site	Montreal	Quebec
Canada	Research Site	Quebec
Canada	Research Site	Québec	Quebec
Canada	Research Site	Trois-Rivières	Quebec
Chile	Research Site	Temuco	Cautín
Chile	Research Site	Vina del Mar	Valparaíso
China	Research Site	Beijing
China	Research Site	Changchun	Jilin
China	Research Site	Chongqing
China	Research Site	Chongqing
China	Research Site	Fuzhou	Fujian
China	Research Site	Fuzhou	Fujian
China	Research Site	Nanjing	Jiangsu
China	Research Site	Shanghai
China	Research Site	Shenyang	Liaoning
China	Research Site	Shijiazhuang	Hebei
China	Research Site	Xi An	Shaanxi
China	Research Site	Xi An	Shaanxi
Croatia	Research Site	Osijek
Croatia	Research Site	Pula
Croatia	Research Site	Rijeka
Croatia	Research Site	Split
Croatia	Research Site	Zagreb
Estonia	Research Site	Tallinn
Estonia	Research Site	Tartu
Greece	Research Site	Athens
Greece	Research Site	Chania
India	Research Site	Bangalore	Karnataka
India	Research Site	Chennai	Tamil Nadu
India	Research Site	Hyderabad	Andhra Pradesh
India	Research Site	Kochi	Kerala
India	Research Site	Mumbai	Maharashtra
India	Research Site	Nashik	Maharashtra
India	Research Site	Nashik	Maharashtra
India	Research Site	Pune	Maharashtra
India	Research Site	Visakhapatnam	Andhra Pradesh
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
Latvia	Research Site	Daugavpils
Latvia	Research Site	Riga
Latvia	Research Site	Riga
Lithuania	Research Site	Kaunas
Lithuania	Research Site	Vilnius
Malaysia	Research Site	Georgetown	Pinang
Malaysia	Research Site	Kuala Lumpur	Wilayah Persekutuan
Malaysia	Research Site	Kuala Lumpur	Wilayah Persekutuan
Malaysia	Research Site	Nilai	Negri Sembilan
Mexico	Research Site	Cuernavaca	Morelos
Mexico	Research Site	Mexico	Distrito Federal
Mexico	Research Site	Mexico City	Distrito Federal
Mexico	Research Site	Oaxaca
Philippines	Research Site	Cebu City
Philippines	Research Site	Davao City	Davao
Philippines	Research Site	Manila
Philippines	Research Site	Manila
Philippines	Research Site	Pasay City
Romania	Research Site	Bucharest
Romania	Research Site	Bucharest
Romania	Research Site	Cluj-Napoca
Romania	Research Site	Cluj-Napoca
Romania	Research Site	Cluj-Napoca
Romania	Research Site	Craiova
Romania	Research Site	Craiova
Romania	Research Site	Lasi
Romania	Research Site	Ploiesti
Romania	Research Site	Suceava
Romania	Research Site	Timisoara
Serbia	Research Site	Belgrade
Serbia	Research Site	Nis
Serbia	Research Site	Sremska Kamenica

Sponsors (1)

Lead Sponsor	Collaborator
Amgen

Countries where clinical trial is conducted

Brazil,  Canada,  Chile,  China,  Croatia,  Estonia,  Greece,  India,  Korea, Republic of,  Latvia,  Lithuania,  Malaysia,  Mexico,  Philippines,  Romania,  Serbia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Survival	Overall survival was defined as the time from the randomization date to the date of death. Participants who had not died by the analysis data cut-off date were censored at their last contact date and participants with survival data obtained after the planned analysis data cut-off date had survival censored at the cut-off date.	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).	No
Secondary	Progression-free Survival	Progression-free survival (PFS) was defined as the time from the randomization date to the date of disease progression per Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1 or death. Progressive disease (PD): At least a 20% increase in the size of target lesions compared with the smallest size since treatment started and an absolute increase of at least 5 mm, any new lesions or an increase in size of non-target lesions thought be = 20% and an absolute increase of at least 5 mm, or significant increase in pleural effusions, ascites or other fluid collections with cytologic proof of malignancy. Participants who were alive and did not meet the criteria for progression by the analysis data cut-off date were censored at their last evaluable disease assessment date.	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).	No
Secondary	Overall Survival in Participants With Wild-type RAS	A secondary efficacy endpoint was overall survival in participants with wild-type rat sarcoma viral oncogene homolog (RAS) (without mutation in exons 2 [codons 12 and 13], 3 [codons 59 and 61], and 4 [codons 117 and 146] of KRAS and neuroblastoma RAS viral oncogene (NRAS)). In participants with wild-type RAS, RAS mutation status was defined by KRAS exon 2 mutation status per clinical trial assay testing and mutation status of KRAS exon 3 and 4 and NRAS exons 2, 3 and 4 per Sanger bi-directional sequencing. Overall survival was defined as the time from the randomization date to the date of death. Participants who had not died by the analysis data cut-off date were censored at their last contact date and participants with survival data obtained after the planned analysis data cut-off date had survival censored at the cut-off date.	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).	No
Secondary	Progression Free Survival (PFS) in Participants With Wild-type RAS	PFS was defined as the time from the randomization date to the date of disease progression per RECIST version 1.1 or death.; Progressive disease (PD): At least a 20% increase in the size of target lesions compared with the smallest size since treatment started and an absolute increase of at least 5 mm, any new lesions, or an increase in size of non-target lesions thought be = 20% with an absolute increase of at least 5 mm, or significant increase in pleural effusions, ascites or other fluid collections with cytologic proof of malignancy. Participants who were alive and did not meet the criteria for progression by the analysis data cut-off date were censored at their last evaluable disease assessment date.	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).	No
Secondary	Objective Response Rate	Objective response rate (ORR) is defined as the percentage of participants with either a complete response (CR) or partial response (PR) per RECIST version 1.1. Radiographic tumor assessments and investigator's assessment of response were performed at Week 4, Week 8, and then every 8 weeks until disease progression (radiographic or clinical progression). CR: Disappearance of all target and non-target lesions and no new lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm. PR: At least a 30% decrease in the size of target lesions with no progression of non-target lesions and no new lesions, or, the disappearance of all target lesions with persistence of one or more non-target lesions not qualifying for either CR or PD and no new lesions.	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).	No
Secondary	Objective Response Rate in Participants With Wild-type RAS	Objective response rate is defined as the percentage of participants with either a complete response (CR) or partial response (PR) per RECIST version 1.1. Radiographic tumor assessments and investigator's assessment of response were performed at Week 4, Week 8, and then every 8 weeks until disease progression (radiographic or clinical progression). CR: Disappearance of all target and non-target lesions and no new lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm. PR: At least a 30% decrease in the size of target lesions with no progression of non-target lesions and no new lesions, or, the disappearance of all target lesions with persistence of one or more non-target lesions not qualifying for either CR or PD and no new lesions.	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).	No
Secondary	Number of Participants With Adverse Events (AEs)	The severity of each AE was graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 (Grade 1 = Mild; 2 = Moderate (discomfort enough to cause interference with usual activity); 3 = Severe (incapacitating with inability to work or do usual activity); 4 = Life-threatening and 5 = Fatal), with the exception of the skin-or nail-related AEs which were graded using a CTCAE version 3.0 with modifications. A serious AE was defined as an AE that met at least 1 of the following criteria: • fatal, • life-threatening, • required in-patient hospitalization or prolongation of existing hospitalization, • resulted in persistent or significant disability/incapacity, • congenital anomaly/birth defect, and/or • other medically important serious event. Treatment-related AEs (TRAEs) are those the investigator considered there was reasonable possibility that the event might have been caused by study drug.	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.	No
Secondary	Maximum Post-baseline Change From Baseline in Corrected QT (QTc) Interval	QT interval is a measure of the time between the start of the Q wave and the end of the T wave in the heart's electrical cycle as measured by electrocardiogram (ECG). QTc is the QT interval corrected for heart rate. To evaluate the effect of panitumumab treatment on the QTc interval length among participants treated with panitumumab, ECGs were collected at the following time points from participants randomized to panitumumab arm at a limited number of sites: Week 1 prior to the first panitumumab infusion (Baseline) and within 30 minutes following the end of the first infusion of panitumumab (Cmax), Week 7 after 3 doses of panitumumab (steady state), and at the safety follow-up visit. The ECGs were submitted for independent central review to calculate the reported QTc interval. QTc was calculated using both the Bazett correction (QTcB) and the Fridericia correction (QTcF).	Baseline (pre-dose), Week 1 and Week 7 (post-dose) and 4 weeks after the last dose (Safety Follow-up visit)	No

External Links

•   AmgenTrials clinical trials website