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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Amgen
ClinicalTrials.gov Identifier:
NCT00819780
First received: November 6, 2008
Last updated: July 14, 2014
Last verified: July 2014
  Purpose

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.


Condition Intervention Phase
Colon Cancer
Colorectal Cancer
Rectal Cancer
Metastatic Colorectal Cancer
Drug: Panitumumab
Drug: Bevacizumab
Drug: mFOLFOX6
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Amgen:

Primary Outcome Measures:
  • Progression-free Survival (PFS) [ Time Frame: From randomization until the data cutoff date of 30 May 2012; median follow-up time was 60 weeks. ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Overall Survival [ Time Frame: From randomization until the data cutoff date of 30 May 2012; median follow-up time was 60 weeks. ] [ Designated as safety issue: No ]
    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. ] [ Designated as safety issue: No ]
    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. ] [ Designated as safety issue: No ]
    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. ] [ Designated as safety issue: No ]
    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. ] [ Designated as safety issue: No ]
    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. ] [ Designated as safety issue: No ]
    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. ] [ Designated as safety issue: No ]
    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. ] [ Designated as safety issue: No ]
    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. ] [ Designated as safety issue: No ]
    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. ] [ Designated as safety issue: No ]
    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. ] [ Designated as safety issue: No ]

    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. ] [ Designated as safety issue: No ]
    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. ] [ Designated as safety issue: No ]
    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.


Enrollment: 285
Study Start Date: April 2009
Estimated Study Completion Date: December 2014
Primary Completion Date: May 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
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: 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.
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.
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00819780

  Show 95 Study Locations
Sponsors and Collaborators
Amgen
Investigators
Study Director: MD Amgen
  More Information

Additional Information:
No publications provided by Amgen

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT00819780     History of Changes
Other Study ID Numbers: 20070509
Study First Received: November 6, 2008
Results First Received: July 10, 2014
Last Updated: July 14, 2014
Health Authority: Belgium: Directorate-General for Medicinal Products
Canada: Health Canada
Germany: Paul_Ehrlich-Institut Bundesamt fur Sera und Impfstoffe
Italy: Local Ethics Committees
Spain: Agencia Española de Medicamentos y Productos Sanitarios
United States: Food and Drug Administration
United States: Quorom Institutional Review Board
United States: Western Institutional Review Board

Keywords provided by Amgen:
Colon Cancer
Colorectal Cancer
Rectal Cancer
Panitumumab
Vectibix
modified FOLFOX 6
mFOLFOX 6
FOLFOX
Bevacizumab
Avastin
First-Line
metastatic

Additional relevant MeSH terms:
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Bevacizumab
Antibodies, Monoclonal
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Growth Inhibitors
Antineoplastic Agents
Therapeutic Uses
Immunologic Factors

ClinicalTrials.gov processed this record on October 19, 2014