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PEAK: Panitumumab Plus mFOLFOX6 vs. Bevacizumab Plus mFOLFOX6 for First Line Treatment of Metastatic Colorectal Cancer (mCRC) Patients With Wild-Type Kirsten Rat Sarcoma-2 Virus (KRAS) Tumors

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ClinicalTrials.gov Identifier: NCT00819780
Recruitment Status : Completed
First Posted : January 9, 2009
Results First Posted : August 6, 2014
Last Update Posted : August 21, 2019
Sponsor:
Information provided by (Responsible Party):
Amgen

Tracking Information
First Submitted Date  ICMJE November 6, 2008
First Posted Date  ICMJE January 9, 2009
Results First Submitted Date  ICMJE July 10, 2014
Results First Posted Date  ICMJE August 6, 2014
Last Update Posted Date August 21, 2019
Actual Study Start Date  ICMJE April 24, 2009
Actual Primary Completion Date May 30, 2012   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 14, 2014)
Progression-free Survival (PFS) [ Time Frame: From randomization until the data cutoff date of 30 May 2012; median follow-up time was 60 weeks. ]
PFS was defined as the time from the date of randomization to the date of first disease progression, or death within 60 days after the last evaluable tumor assessment or randomization date (whichever was later). Participants not meeting the criteria by the cutoff date were censored at the last evaluable tumor assessment date. Tumor response was evaluated by the investigator per modified Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0 every 8 weeks until radiographic disease progression. Progression is defined as at least a 20% increase in the size of target lesions, unequivocal progression of existing non-target lesions, or any new lesions.
Original Primary Outcome Measures  ICMJE
 (submitted: January 8, 2009)
Progression-free Survival (PFS) [ Time Frame: 37 months ]
Change History Complete list of historical versions of study NCT00819780 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: July 14, 2014)
  • Overall Survival [ Time Frame: From randomization until the data cutoff date of 30 May 2012; median follow-up time was 60 weeks. ]
    Overall survival was defined as the time from randomization to the date of death, with participants alive or lost to follow-up at the analysis data cutoff date censored at their last contact date.
  • Percentage of Participants With an Objective Response [ Time Frame: From randomization until the data cutoff date of 30 May 2012; median follow-up time was 60 weeks. ]
    Objective response was defined as having a confirmed complete response (CR) or partial response (PR) during first-line treatment, based on the investigator's review of scans using a modified-RECIST v1.0. A complete or partial response was confirmed no less than 4-weeks after the criteria for response were first met. Complete Response: Disappearance of all target and non-target lesions and no new lesions. Partial Response: At least a 30% decrease in the sum of the longest diameter (SLD) of target lesions and 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 lesion(s) not qualifying for either CR or progressive disease and no new lesions.
  • Duration of Response [ Time Frame: From randomization until the data cutoff date of 30 May 2012; median follow-up time was 60 weeks. ]
    For participants with a confirmed objective response, the time from first confirmed objective response to radiologic disease progression per modified RECIST 1.0 criteria or death. For participants who responded and have not progressed or died, duration of response was censored at their last evaluable disease assessment date.
  • Time to Disease Progression [ Time Frame: From randomization until the data cutoff date of 30 May 2012; median follow-up time was 60 weeks. ]
    Time to progression (TTP) is defined as the time from randomization to the date of radiologic disease progression per modified RECIST 1.0 criteria. Participants not meeting criteria for disease progression by the analysis data cutoff date were censored at their last evaluable disease assessment date. Progression is defined as at least a 20% increase in the size of target lesions, unequivocal progression of existing non-target lesions, or any new lesions.
  • Time to Initial Objective Response [ Time Frame: From randomization until the data cutoff date of 30 May 2012; median follow-up time was 60 weeks. ]
    For participants with a confirmed objective response, the time from randomization to the date of first confirmed objective response. Assessments are based on the investigator's review of scans using a modified-RECIST v1.0. An objective response is defined as a best tumor response of complete or partial response. A complete or partial response was confirmed no less than 4-weeks after the criteria for response were first met.
  • Resection Rate [ Time Frame: From randomization until the data cutoff date of 30 May 2012; median follow-up time was 60 weeks. ]
    The resection rate was defined as the percentage of participants with a surgical procedure that resulted in partial reduction or complete eradication of all metastatic disease.
  • Progression-free Survival (PFS) in Participants With Wild-type Rat Sarcoma Viral Oncogene Homolog (RAS) [ Time Frame: From randomization until the data cutoff date of 30 May 2012; median follow-up time was 60 weeks. ]
    PFS was defined as the time from the date of randomization to the date of first disease progression, or death within 60 days after the last evaluable tumor assessment or randomization date (whichever was later). Participants not meeting the criteria by the cutoff date were censored at the last evaluable tumor assessment date. Tumor response was evaluated by the investigator per modified Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0 every 8 weeks until radiographic disease progression. Progression is defined as at least a 20% increase in the size of target lesions, unequivocal progression of existing non-target lesions, or any new lesions.
  • Progression-free Survival (PFS) in Participants With Wild-type RAS / V-raf Murine Sarcoma Viral Oncogene Homolog B1 (BRAF) [ Time Frame: From randomization until the data cutoff date of 30 May 2012; median follow-up time was 60 weeks. ]
    PFS was defined as the time from the date of randomization to the date of first disease progression, or death within 60 days after the last evaluable tumor assessment or randomization date (whichever was later). Participants not meeting the criteria by the cutoff date were censored at the last evaluable tumor assessment date. Tumor response was evaluated by the investigator per modified Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0 every 8 weeks until radiographic disease progression. Progression is defined as at least a 20% increase in the size of target lesions, unequivocal progression of existing non-target lesions, or any new lesions.
  • Overall Survival in Participants With Wild-type RAS [ Time Frame: From randomization until the data cutoff date of 30 May 2012; median follow-up time was 60 weeks. ]
    Overall survival was defined as the time from randomization to the date of death, with participants alive or lost to follow-up at the analysis data cutoff date censored at their last contact date.
  • Overall Survival in Participants With Wild-type RAS / BRAF [ Time Frame: From randomization until the data cutoff date of 30 May 2012; median follow-up time was 60 weeks. ]
    Overall survival was defined as the time from randomization to the date of death, with participants alive or lost to follow-up at the analysis data cutoff date censored at their last contact date.
  • Percentage of Participants With an Objective Response for Participants With Wild-type RAS [ Time Frame: From randomization until the data cutoff date of 30 May 2012; median follow-up time was 60 weeks. ]
    Objective response was defined as having a confirmed complete response (CR) or partial response (PR) during first-line treatment, based on the investigator's review of scans using a modified-RECIST v1.0. A complete or partial response was confirmed no less than 4-weeks after the criteria for response were first met. Complete Response: Disappearance of all target and non-target lesions and no new lesions. Partial Response: At least a 30% decrease in the sum of the longest diameter (SLD) of target lesions and 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 lesion(s) not qualifying for either CR or progressive disease and no new lesions.
  • Percentage of Participants With an Objective Response for Participants With Wild-type RAS / BRAF [ Time Frame: From randomization until the data cutoff date of 30 May 2012; median follow-up time was 60 weeks. ]
    Objective response was defined as having a confirmed complete response (CR) or partial response (PR) during first-line treatment, based on the investigator's review of scans using a modified-RECIST v1.0. A complete or partial response was confirmed no less than 4-weeks after the criteria for response were first met. Complete Response: Disappearance of all target and non-target lesions and no new lesions. Partial Response: At least a 30% decrease in the sum of the longest diameter (SLD) of target lesions and 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 lesion(s) not qualifying for either CR or progressive disease and no new lesions.
  • Number of Participants With Adverse Events (AEs) [ Time Frame: The time frame for adverse event reporting is from the first dose date to 30 days since the last dose date. The median time frame is 8.0 months for Panitumumab Plus mFOLFOX arm and 7.3 months for Bevacizumab Plus mFOLFOX6 arm. ]
    Severity was graded using Common Terminology Criteria for Adverse Events (CTCAE) v3.0, with the exception of some dermatology/skin adverse events that were graded using CTCAE v3.0 with modifications. Fatal adverse events are classified as grade 5. 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 were those that the investigator considered a reasonable possibility that might have been caused by study drug.
Original Secondary Outcome Measures  ICMJE
 (submitted: January 8, 2009)
Overall survival (OS), objective response (OR), duration of response (DOR), time to progression (TTP), time to response (TTR) and resectability [ Time Frame: 53 months ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE PEAK: Panitumumab Plus mFOLFOX6 vs. Bevacizumab Plus mFOLFOX6 for First Line Treatment of Metastatic Colorectal Cancer (mCRC) Patients With Wild-Type Kirsten Rat Sarcoma-2 Virus (KRAS) Tumors
Official Title  ICMJE A Randomized, Multicenter, Phase 2 Study to Compare the Efficacy of Panitumumab in Combination With mFOLFOX6 to the Efficacy of Bevacizumab in Combination With mFOLFOX6 in Patients With Previously Untreated, KRAS Wild-Type, Unresectable, Metastatic Colorectal Cancer
Brief Summary The primary objective of this study is to estimate the treatment effect on progression-free survival (PFS) of panitumumab relative to bevacizumab in combination with mFOLFOX6 chemotherapy as first-line therapy in patients with tumors expressing wild-type KRAS, unresectable mCRC.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Colon Cancer
  • Colorectal Cancer
  • Rectal Cancer
  • Metastatic Colorectal Cancer
Intervention  ICMJE
  • Drug: Panitumumab
    Panitumumab is a fully human immunoglobulin G (IgG)2 monoclonal antibody antagonist directed against human Epidermal Growth Factor receptor (EGFr).
    Other Name: Vectibix
  • Drug: Bevacizumab
    Bevacizumab is a humanized monoclonal IgG1 antibody that is directed against Vascular Endothelial Growth Factor (VEGF).
    Other Name: Avastin
  • Drug: mFOLFOX6
    mFOLFOX6 regimen is a combination therapy of oxaliplatin (85 mg/m^2) administered as a 2-hour infusion on Day 1; leucovorin (400 mg/m^2) administered as a 2-hour infusion on Day 1; followed by a loading dose of 5-fluorouracil (5-FU; 400 mg/m^2) IV bolus administered over approximately 2 to 4 minutes on Day 1, then 5- FU (2400 mg/m^2) via ambulatory pump administered for a period of 46 to 48 hours.
Study Arms  ICMJE
  • Experimental: Panitumumab Plus mFOLFOX6
    Participants received 6 mg/kg panitumumab administered by intravenous (IV) infusion and modified FOLFOX6 (mFOLFOX6) chemotherapy regimen consisting of oxaliplatin (85 mg/m^2), leucovorin (400 mg/m^2) and 5-fluorouracil (5-FU) (2400 mg/m^2) administered on Day 1 of every 14-day cycle until disease progression, unacceptable toxicity, withdrawal of consent, or death.
    Interventions:
    • Drug: Panitumumab
    • Drug: mFOLFOX6
  • Active Comparator: Bevacizumab Plus mFOLFOX6
    Participants received 5 mg/kg bevacizumab administered by IV infusion and the mFOLFOX6 regimen consisting of oxaliplatin (85 mg/m^2), leucovorin (400 mg/m^2), followed by 5-FU (2400 mg/m^2) administered on Day 1 of every 14-day cycle until disease progression, unacceptable toxicity, withdrawal of consent, or death.
    Interventions:
    • Drug: Bevacizumab
    • Drug: mFOLFOX6
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: December 14, 2011)
285
Original Estimated Enrollment  ICMJE
 (submitted: January 8, 2009)
280
Actual Study Completion Date  ICMJE July 7, 2016
Actual Primary Completion Date May 30, 2012   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Histologically or cytologically-confirmed adenocarcinoma of the colon or rectum in patients with unresectable metastatic (M1) disease
  • Patients with at least 1 uni-dimensionally measurable lesion of at least 10 mm per modified Response Evaluation Criteria in Solid Tumors (RECIST) guidelines
  • Wild-type KRAS tumor status confirmed by an Amgen approved central laboratory or an experienced laboratory (local laboratory) per local regulatory guidelines using a validated test method
  • Eastern Cooperative Oncology Group (ECOG) score of 0 or 1
  • Men or women 18 years of age or older
  • Adequate hematologic, renal, hepatic, metabolic, and coagulation function

Exclusion Criteria:

  • History of prior or concurrent central nervous system (CNS) metastases
  • Prior chemotherapy or other systemic anticancer therapy for treatment of metastatic colorectal carcinoma
  • Clinically significant cardiac disease
  • Clinically significant peripheral sensory neuropathy
  • Active inflammatory bowel disease
  • Recent gastroduodenal ulcer to be active or uncontrolled
  • History of interstitial lung disease
  • Recent pulmonary embolism, deep vein thrombosis, or other significant venous event
  • Pre-existing bleeding diathesis and/or coagulopathy with exception of well-controlled anticoagulation therapy
  • Recent major surgical procedure, open biopsy, or significant traumatic injury not yet recovered from prior major surgery.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States,   Belgium,   Canada,   Germany,   Italy,   Spain
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00819780
Other Study ID Numbers  ICMJE 20070509
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Amgen
Study Sponsor  ICMJE Amgen
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: MD Amgen
PRS Account Amgen
Verification Date August 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP